[go: up one dir, main page]

US20050256525A1 - Dilation introducer for orthopedic surgery - Google Patents

Dilation introducer for orthopedic surgery Download PDF

Info

Publication number
US20050256525A1
US20050256525A1 US11/038,784 US3878405A US2005256525A1 US 20050256525 A1 US20050256525 A1 US 20050256525A1 US 3878405 A US3878405 A US 3878405A US 2005256525 A1 US2005256525 A1 US 2005256525A1
Authority
US
United States
Prior art keywords
dilator tube
dilation introducer
distal
proximal
dilation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
US11/038,784
Inventor
Brad Culbert
Fausto Olmos
Christopher Warren
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Interventional Spine Inc
Original Assignee
Triage Medical Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Triage Medical Inc filed Critical Triage Medical Inc
Assigned to TRIAGE MEDICAL INC. reassignment TRIAGE MEDICAL INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CULBERT, BRAD, OLMOS, FAUSTO, WARREN, CHRISTOPHER
Priority to US11/659,025 priority Critical patent/US9387313B2/en
Priority to EP05777628.8A priority patent/EP1773438B1/en
Priority to EP16207090.8A priority patent/EP3205371B1/en
Priority to PCT/US2005/027431 priority patent/WO2006017507A2/en
Priority to JP2007524917A priority patent/JP5164571B2/en
Publication of US20050256525A1 publication Critical patent/US20050256525A1/en
Assigned to INTERVENTIONAL SPINE, INC. reassignment INTERVENTIONAL SPINE, INC. CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: TRIAGE MEDICAL, INC.
Priority to US15/186,963 priority patent/US10293147B2/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y113/00—Oxidoreductases acting on single donors with incorporation of molecular oxygen (oxygenases) (1.13)
    • C12Y113/12—Oxidoreductases acting on single donors with incorporation of molecular oxygen (oxygenases) (1.13) with incorporation of one atom of oxygen (internal monooxygenases or internal mixed function oxidases)(1.13.12)
    • C12Y113/12007—Photinus-luciferin 4-monooxygenase (ATP-hydrolysing) (1.13.12.7), i.e. firefly-luciferase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1034—Isolating an individual clone by screening libraries
    • C12N15/1048—SELEX
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1135—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against oncogenes or tumor suppressor genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1136—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against growth factors, growth regulators, cytokines, lymphokines or hormones
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1137—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against enzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1138—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against receptors or cell surface proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y502/00—Cis-trans-isomerases (5.2)
    • C12Y502/01—Cis-trans-Isomerases (5.2.1)
    • C12Y502/01008—Peptidylprolyl isomerase (5.2.1.8), i.e. cyclophilin
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
    • G16B20/20—Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16B—BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY
    • G16B20/00—ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
    • G16B20/50—Mutagenesis
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/10—Applications; Uses in screening processes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00—Applications; Uses
    • C12N2320/10—Applications; Uses in screening processes
    • C12N2320/11—Applications; Uses in screening processes for the determination of target sites, i.e. of active nucleic acids

Definitions

  • This invention relates to bone fixation devices, and more particularly relates to a dilation introducer for introducing a bone fixation device for orthopedic surgery, such as for vertebral fusion.
  • Fusion of two adjacent vertebrae is a common surgical treatment for back injuries due to damage or defects in a spinal disc between two adjacent vertebrae, such as conditions due to a herniated disc or disc degeneration.
  • the entire disc may be removed by a discectomy procedure, and may be replaced with bone or a bone substitute and/or cage in order to prevent collapse of the disc space between the adjacent vertebrae.
  • Early techniques for stabilizing the adjacent vertebrae included application of a plate or a rod in conjunction with screws across the adjacent vertebrae, after which the adjacent vertebrae would eventually fuse together. However, such techniques commonly required prolonged periods of recovery from the extensive surgery involved, and it would be desirable to provide an improved apparatus and method for providing a minimally invasive procedure that will result in less trauma and improvement in patient recovery.
  • Bone fixation devices are known that are useful for connecting two or more bone segments for the healing of broken bones, typically including an elongate pin with a distal anchor and a proximal anchor movable on the pin to accommodate different bone dimensions, and to permit tensioning of the bone segments together.
  • the surgical procedure of attaching two or more parts of a bone with a pin-like device commonly requires an initial incision into the tissue down to the bone, and the drilling of a hole through the bone parts to be joined.
  • Such bone fixation devices can be useful for fusion of vertebrae together, because such a bone fixation device can be used to join adjacent bone segments through a single percutaneous incision or puncture, without the need to expose any other side of the bone segments to be joined.
  • the invention provides for a telescoping dilation introducer for orthopedic surgery, the dilation introducer having a locked assembled configuration for initial placement of the dilation introducer against a patient's tissue to be treated, and an unlocked, collapsed configuration for dilating the patient's soft surrounding tissue to a desired degree of dilation to permit minimally invasive surgical procedures on the patient's tissue.
  • each individual dilator tube is successively released and advanced to progressively expand the patient's soft tissue down to the tissue to be treated.
  • the tissue to be treated is bone tissue which must be prepared prior to attachment of adjacent bone section in a fusion process.
  • the invention is particularly applicable to fusion of bones in orthopedic surgery using minimally invasive technique, and will be described herein in particular applications of those procedures.
  • the invention also concerns a minimally invasive procedure utilizing the telescoping dilation introducer to insert a bone fixation device into a patient's spine for posterior spine fusion. While posterior spine fusion currently takes up to two hours to complete, and requires a six inch incision, with the apparatus and method of the invention, comparable surgery can be completed in less than thirty minutes, with a dilation port 13 mm or less in diameter, thus lowering the chance of damage to the surrounding soft tissue.
  • a telescoping dilation introducer is typically operated by pressing the introducer against a relatively hard surface, such as bone tissue being treated.
  • the present invention provides for a guide wire assembly when such a telescoping dilation introducer is to used in treatment of soft tissue, such as an organ, to provide a surface against which the telescoping dilation introducer can be pushed during operation of the telescoping dilation introducer.
  • a guide wire or K wire assembly is provided for use with a telescoping dilation introducer according to the invention.
  • the guide wire assembly includes an elongated generally cylindrical first section, and an elongated tubular second section that receives the first section.
  • the elongated generally cylindrical first section includes a proximal enlarged head or stop portion, and an elongated body portion with a proximal section and a relatively narrower diameter main section connected to the proximal section, and a pointed distal tip at the distal end of the narrow main section.
  • the second section of the guide wire assembly includes an elongated tubular body with an internal bore adapted to receive the narrow main section, as is illustrated in FIG. 28 .
  • the tubular second section advantageously includes a frustoconical distal tip with a narrowed portion at the distal end and an enlarged flat shoulder at the proximal end of the frustoconical distal tip.
  • the assembly When the guide wire assembly is assembled, the assembly presents a pointed distal end with a proximal shoulder against which a telescoping dilation introducer can be pushed for operation of the telescoping dilation introducer.
  • the main section thus adds a sharp point to the relatively blunt distal end of the tubular distal section, allowing the guide wire assembly to be inserted through soft tissue for placement in a soft tissue target of interest, such as an organ, and the first section can then be removed to allow a telescoping dilation introducer to be placed over the second section and pressed against the shoulder of the blunt distal end for operation of the telescoping dilation introducer.
  • the first section can be removed from the second section, leaving the blunt distal end in place at the desired location in the soft tissue, and the telescoping dilation introducer can be placed over the second section and pressed against the shoulder of the blunt distal end for operation of the telescoping dilation introducer.
  • the present invention provides for an improvement in a dilation introducer for orthopedic surgery, in which the dilation introducer includes one or more dilator tubes having a distal end and a proximal end, and the distal end of the one or more dilator tubes including a plurality of spikes for engaging bone tissue.
  • the spikes may be formed of radiopaque material, for fluoroscopic imaging of the positioning of the one or more dilator tubes, and the spikes may be formed with a rounded shape so as to deflect soft tissue.
  • the dilation introducer includes a parallel guide insert adapted to be received in the one or more dilator tubes.
  • the parallel guide insert includes a main cylindrical shaft having a proximal end connected to a cylindrical head, and a plurality of longitudinal bores extending the length of the parallel guide insert through the main cylindrical shaft and cylindrical head.
  • the distal tip of the parallel guide insert may be provided with a plurality of spikes for engaging bone tissue.
  • the spikes of the parallel guide insert may be formed of radiopaque material, and may be formed with a rounded shape so as to deflect soft tissue.
  • the present invention concerns a dilation introducer for orthopedic surgery having a locked assembled configuration for initial placement of the dilation introducer against a patient's bone tissue to be treated, and an unlocked, collapsed configuration dilating the patient's soft tissue down to the bone tissue to be treated to a desired degree of dilation to permit minimally invasive surgical procedures on the patient's bone tissue to be treated.
  • the dilation introducer includes a first dilator tube having a distal end with a tapered tip and a proximal end with a cylindrical head, and a second dilator tube having a distal end with a tapered tip and a proximal end with a cylindrical head, and an inner lumen with a distal opening and a proximal opening.
  • the first dilator tube is removably received in the second dilator tube for slidable telescoping movement within the second dilator tube.
  • Means are provided for removably connecting the first and second dilator tubes together in a locked configuration.
  • the means for removably connecting the first and second dilator tubes includes a first latching member disposed in the cylindrical head of the first dilator tube.
  • the first latching member has a locking button connected transversely to a shaft with a latching end projecting from the cylindrical head of the first dilator tube toward the distal end of the first dilator tube, with the locking button extending transversely from the shaft through a side aperture in the cylindrical head of the first dilator tube.
  • the locking button is biased outwardly from the cylindrical head, such as by a spring, and the first latching member is received in an upper aperture of the cylindrical head of an adjacent second dilator tube.
  • the upper aperture of the cylindrical head of the second dilator tube includes a latching chamber for retaining the latching end of the latching member when the locking button is biased outwardly, to lock the cylindrical heads of the first and second dilator tubes together.
  • the locking button is moveable inwardly to move the latching member inwardly and to move the latching end of the latching member inwardly out of the latching chamber, to unlock the first and second dilator tubes.
  • the dilation introducer may include one or more additional dilator tubes, with the second dilator tube being removably received in the one or more additional dilator tubes for slidable telescoping movement within the one or more additional dilator tubes.
  • the one or more additional dilator tubes likewise have a distal end and a proximal end with a cylindrical head, an inner lumen with a distal opening and a proximal opening, and the distal end having a tapered tip.
  • the second dilator tube and the one or more additional dilator tubes having an unlocked configuration in which the one or more additional dilator tubes may slidably telescope over the second dilator tube to dilate the patient's soft tissue at the distal end of the dilation introducer.
  • Means are provided for removably connecting the second dilator tube and the one or more additional dilator tubes together in a locked configuration.
  • the means for removably connecting the second dilator tube and the one or more additional dilator tubes include a second latching member disposed in the cylindrical head of the second dilator tube.
  • the second latching member has a locking button connected transversely to a shaft with a latching end projecting from the cylindrical head of the second dilator tube toward the distal end of the second dilator tube, and the locking button extends transversely from the shaft through a side aperture in the cylindrical head of the second dilator tube.
  • the locking button is biased outwardly from the cylindrical head, such as by a spring, and the second latching member is received in an upper aperture of the cylindrical head of the additional dilator tube to be connected.
  • the upper aperture of the cylindrical head of the additional dilator tubes include a latching chamber for retaining the latching end of the second latching member when the locking button is biased outwardly, to lock the cylindrical heads of the second and additional dilator tube together, and the locking button is moveable inwardly to move the second latching member inwardly and the latching end of the second latching member inwardly out of the latching chamber.
  • the additional dilator tube comprises a handle connected to the proximal end of the additional dilator tube, and the cylindrical head of the additional dilator tube includes a plurality of the upper apertures, each including a latching chamber for receiving the second latching member.
  • the present invention provides for an improvement in a dilation introducer for orthopedic surgery, in which the dilation introducer includes a dilator tube having a tubular shaft, a distal end and a proximal end, an inner lumen with a distal opening and a proximal opening, and a light emitter disposed in the dilator tube.
  • the light emitter may be a light emitting diode, and the light emitting diode may be embedded in the tubular shaft of the dilator tube.
  • the light emitter may include a fiber optic, and the fiber optic may be embedded in the tubular shaft of the dilator tube.
  • the dilator tube includes a handle and a switch for controlling the light emitter, and at least one battery is disposed in the handle and is connected to the switch to power the light emitter.
  • the light emitter includes one or more fiber optics
  • the light emitter includes a light source providing light conducted to the one or more fiber optics.
  • the light emitter may include one or more elongated energy conducting members disposed on an outer surface of the tubular shaft of the dilator tube, and the one or more elongated energy conducting members may be disposed in a groove on the exterior surface of the tubular shaft.
  • the one or more elongated energy conducting members may be located on the inside of the dilator tube, or may extend through the wall of the dilator tube.
  • the present invention also provides for a telescoping expander sleeve adapted to be slidably disposed over a shaft of a dilator tube for dilating a patient's soft tissue down to a bone tissue to be treated to a desired degree of dilation to permit minimally invasive surgical procedures on the patient's bone tissue.
  • the telescoping expander sleeve is moveable between an extended, unexpanded configuration and a collapsed, expanded configuration.
  • the telescoping expander sleeve includes a first generally tubular section having a tubular proximal portion and a distal portion.
  • the tubular proximal portion has an enlarged proximal head, and the distal portion includes two or more active spreader arms each having a proximal end and a distal tip.
  • the tubular proximal portion may optionally be provided with a handle.
  • the two or more active spreader arms are connected at their proximal ends to the tubular proximal portion, and the distal tips of the two or more active spreader arms are moveable radially between an unexpanded configuration and an expanded configuration.
  • the telescoping expander sleeve also includes a second generally tubular section slidably disposed over the first generally tubular section.
  • the second generally tubular section includes a tubular proximal portion and a distal portion including two or more passive spreader flaps each having a narrow proximal end and a wide distal tip.
  • the proximal ends of the two or more passive spreader flaps are hingedly connected to the tubular proximal portion, and the distal tips of the two or more passive spreader flaps are moveable radially between an unexpanded configuration and an expanded configuration.
  • the two or more active spreader arms slidably engage the two or more passive spreader flaps, so that as the telescoping expander sleeve telescopes from the extended, unexpanded configuration to the collapsed, expanded configuration, the two or more active spreader arms slide from the narrow proximal ends of the two or more passive spreader flaps to the wider distal ends of the passive spreader flaps to spread the distal ends of the two or more passive spreader flaps apart, and to spread the distal ends of the two or more active spreader arms apart.
  • the distal tips of the two or more active spreader arms have beveled edges to deflect soft tissue during insertion of the telescoping expander sleeve
  • the distal tips of the two or more passive spreader flaps have beveled edges to deflect soft tissue during insertion of the telescoping expander sleeve.
  • the purpose of the active spreader arms and passive spreader flaps is to facilitate the creating of a larger working area adjacent to bone or bone tissues being treated.
  • the spreader arms and flaps may optionally be covered by an expandable material, such as latex, for example, to prevent tissues from being pressed into cavities of the telescoping expander sleeve.
  • the present invention is particularly useful for the purposes of orthopedic surgery, those skilled in the art will recognize that the invention can also be used for the treatment of a variety of internal organs or structures when it is desired to minimize the size of an opening in the patient's soft tissue and the resultant damage and trauma to tissue surrounding the operation site.
  • FIG. 1 is a plan view of a first embodiment of a dilation introducer in a locked configuration, according to the present invention.
  • FIG. 2 is a plan view of the dilation introducer of FIG. 1 shown in an unlocked, collapsed configuration.
  • FIG. 3 is a plan view of the first or inner dilator tube of the dilation introducer of FIG. 1 .
  • FIG. 4 is a plan view of the second or intermediate dilator tube of the dilation introducer of FIG. 1 .
  • FIG. 5 is a plan view of the third or outer dilator tube of the dilation introducer of FIG. 1 .
  • FIG. 6A is a top plan view of the first locking clip of the dilation introducer of FIG. 1 .
  • FIG. 6B is an elevational view of the first locking clip of the dilation introducer of FIG. 1 .
  • FIG. 6C is a bottom plan view of the first locking clip of the dilation introducer of FIG. 1 .
  • FIG. 7A is a top plan view of the second locking clip of the dilation introducer of FIG. 1 .
  • FIG. 7B is an elevational view of the second locking clip of the dilation introducer of FIG. 1 .
  • FIG. 8 is a perspective view of a second embodiment of a dilation introducer in a locked configuration, according to the present invention.
  • FIG. 9 is a perspective view of the dilation introducer of FIG. 8 shown in an unlocked, collapsed configuration.
  • FIG. 10 is a perspective view of the first or inner dilator tube of the dilation introducer of FIG. 8 .
  • FIG. 11 is a perspective view of the second or intermediate dilator tube of the dilation introducer of FIG. 8 .
  • FIG. 12 is a plan view of the third or outer dilator tube of the dilation introducer of FIG. 8 .
  • FIG. 13 is a plan view of a third embodiment of a dilation introducer in a locked configuration, according to the present invention.
  • FIG. 14 is a plan view of the dilation introducer of FIG. 13 shown in an unlocked, collapsed configuration.
  • FIG. 15 is a plan view of the first or inner dilator tube of the dilation introducer of FIG. 13 .
  • FIG. 16 is a plan view of the second or intermediate dilator tube of the dilation introducer of FIG. 13 .
  • FIG. 17 is a plan view of the third or outer dilator tube of the dilation introducer of FIG. 13 .
  • FIG. 18 is a plan view of the plastic sleeve of the dilation introducer of FIG. 13 .
  • FIG. 19 is a plan view of a fourth embodiment of a dilation introducer in a locked configuration, according to the present invention.
  • FIG. 20 is a plan view of the dilation introducer of FIG. 19 shown in an unlocked, collapsed configuration.
  • FIG. 21 is a plan view of the first or inner dilator tube of the dilation introducer of FIG. 19 .
  • FIG. 22 is a plan view of the second or intermediate dilator tube of the dilation introducer of FIG. 19 .
  • FIG. 23 is a plan view of the third or outer dilator tube of the dilation introducer of FIG. 19 .
  • FIG. 24 is a schematic diagram illustrating location of a starting point for insertion of a bone fixation device according to the method of the invention.
  • FIG. 25 is a schematic diagram of a lateral view illustrating location of a trajectory for insertion of a bone fixation device according to the method of the invention.
  • FIG. 26 is a schematic diagram of an anterior view illustrating location of a trajectory for insertion of a bone fixation device according to the method of the invention.
  • FIG. 27 is a plan view of a guide wire assembly for use with the various embodiments of the telescoping dilation introducer of the invention, shown disassembled.
  • FIG. 28 is a plan view of the guide wire assembly of FIG. 27 , shown partially assembled.
  • FIG. 29 is a plan view of the guide wire assembly of FIG. 27 , shown fully assembled.
  • FIG. 30 is a perspective view of a variation of the outer dilator tube of the embodiment of FIGS. 8-12 , with a parallel guide.
  • FIG. 31 is a perspective view of the parallel guide from FIG. 30 .
  • FIG. 32 is a perspective view of a variation of the outer dilator tube of the embodiment of FIGS. 8-12 , with an angled tip and with a parallel guide.
  • FIG. 33 is a perspective view of the parallel guide with an angled tip from FIG. 32 .
  • FIG. 34 is a perspective of another variation of the outer dilator tube of the embodiment of FIGS. 8-12 , with an angled tip and spikes.
  • FIG. 35 is a perspective view of the outer dilator tube of FIG. 34 , with a parallel guide with spikes.
  • FIG. 36 is a perspective view of a fifth embodiment of a dilation introducer in an unlocked configuration, according to the present invention.
  • FIG. 37 is a sectional view of a portion of the dilation introducer of FIG. 36 .
  • FIG. 38 is a perspective view of a variation of the dilation introducer of FIG. 36 , shown in a locked configuration, according to the present invention.
  • FIG. 39 is a sectional view of a portion of the dilation introducer of FIG. 36 taken along line 39 - 39 of FIG. 38 .
  • FIG. 40 is a top perspective view of the head end of the handle of the dilation introducer of FIG. 36 , showing multiple locking locations.
  • FIG. 41 is a schematic diagram of a variation of the dilation introducer of FIG. 36 , with a light emitter and switch for the light emitter.
  • FIG. 42 is an enlarged view of the tip of the dilation introducer of FIG. 41 .
  • FIG. 43 is a perspective view of another variation of the dilation introducer of FIG. 41 , with an exterior groove for one or more elongated energy conducting members.
  • FIG. 44 is a side elevational view of a telescoping expander sleeve shown in an extended, unexpanded configuration.
  • FIG. 45 is a side elevational view of the telescoping expander sleeve of FIG. 44 shown in an intermediate partially collapsed, partially expanded configuration.
  • FIG. 46 is a side elevational view of the telescoping expander sleeve of FIG. 44 shown in a fully collapsed, fully expanded configuration.
  • the present invention provides for a telescoping dilation introducer for orthopedic surgery, the dilation introducer having a locked assembled configuration for initial placement of the dilation introducer against a patient's bone tissue to be treated, and an unlocked, collapsed configuration dilating the patient's soft tissue down to the bone tissue to be treated to a desired degree of dilation to permit minimally invasive surgical procedures on the patient's bone tissue to be treated.
  • a dilation introducer 30 according to a first preferred embodiment is shown in a locked assembled configuration in FIG. 1 , and shown in an unlocked, collapsed configuration in FIG. 2 .
  • the dilation introducer includes a first or inner dilator tube 32 having a distal end 34 with a tapered tip 36 , and a proximal end 38 with a head 40 including a pair of spaced part rings 42 .
  • the first dilator tube has an inner lumen 44 with a distal opening 46 and a proximal opening 48 .
  • the dilation introducer also includes a shorter second or intermediate dilator tube 52 having a distal end 54 with a tapered tip 56 , and a proximal end 58 with a head 60 including a pair of spaced apart rings 62 .
  • the second dilator tube has an inner lumen 64 with a distal opening 66 and a proximal opening 68 .
  • the dilation introducer also includes at least one additional dilator tube, such as a still shorter third or outer dilator tube 72 having a distal end 74 with a tapered tip 76 , and a proximal end 78 with a handle 80 .
  • the third dilator tube has an inner lumen 82 with a distal opening 84 and a proximal opening 86 .
  • the means for removably connecting the first and second dilator tubes together in a locked configuration includes a first locking clip 88 .
  • a means for removably connecting the second and third dilator tubes together in a locked configuration may also be provided, and may include a second locking clip 90 .
  • the first locking clip includes a first portion 92 and a second portion 94 , and a cross-piece or handle 96 having a first end 98 and a second end 100 connected at right angles between the first and second portions.
  • the first portion includes pair of resilient arms 102 each having a proximal narrow neck portion 104 connected to the cross-piece, and a distal gripping portion 106 extending from the narrow neck portion.
  • the resilient arms have an inner rounded surface 108 adapted to snap over the first dilator tube between the spaced apart rings of the first dilator tube.
  • the second portion currently preferably includes a single arm 112 having a proximal narrow neck portion 114 , and a distal gripping portion 116 extending from the narrow neck portion.
  • the gripping portion has an inner rounded surface 118 adapted to fit over the outer surface of the second dilator tube between the spaced apart rings of the second dilator tube, to connect the first and second dilator tubes. Removing the first locking clip allows the second or intermediate dilator tube to slidably telescope over the first inner dilator tube to dilate tissue at the distal end of the dilation introducer.
  • the second locking clip includes a first portion 122 and a second portion 124 , and a cross-piece or handle 126 having a first end 128 and a second end 130 connected between the first portion and the second portion at right angles.
  • the first portion includes a pair of resilient arms 132 each having a proximal narrow neck portion 134 connected to the cross-piece, and a distal gripping portion 136 extending from the narrow neck portion.
  • the pair of resilient arms have an inner rounded surface 138 adapted to snap over the outer surface of the second dilator tube between the spaced apart rings of the second dilator tube.
  • the second portion of the second locking clip includes a pair of resilient arms 142 each having a proximal narrow neck portion (not shown) connected to the cross-piece and a distal gripping portion 146 extending from the narrow neck portion, the pair of resilient arms having an inner rounded surface (not shown) adapted to fit over the outer surface of the third dilator tube to connect the second and third dilator tubes. Removing the second locking clip allows the third or outer dilator tube to slidably telescope over the second inner dilator tube to further dilate tissue at the distal end of the dilation introducer.
  • a tubular bone drill or tap 150 can be inserted through an intermediate or outer dilator tube, and the tubular bone drill or tap can be passed or threaded over a guide wire or K wire 151 to contact the surface of the vertebra or bone to be treated, as will be further described below.
  • the inner dilator tube, the tubular bone drill, and the intermediate dilator tube can be withdrawn and removed to leave the outer dilator tube in place to permit further surgical procedures.
  • the invention provides for a second presently preferred embodiment of a dilation introducer 160 shown in a locked assembled configuration in FIG. 8 , and shown in an unlocked, collapsed configuration in FIG. 9 .
  • the dilation introducer includes a first or inner dilator tube 162 having a distal end 164 with a tapered tip 166 , and a proximal end 168 with a cylindrical head 170 .
  • the means for removably connecting the first and second dilator tubes together in a locked configuration includes a latching member 172 , such as a hook, projecting from the cylindrical head toward the distal end, receiving a locking pin 216 , although other latching members, such as a projection with aperture for receiving a locking pin may also be suitable, as will be apparent from the explanation below.
  • the first dilator tube has an inner lumen 174 with a distal opening 176 and a proximal opening 178 .
  • the dilation introducer includes a shorter second or intermediate dilator tube 182 having a distal end 184 with a tapered tip 186 , and a proximal end 188 having a cylindrical head 190 .
  • the means for removably connecting the second and third dilator tubes together in a locked configuration includes a latching member 192 , such as a hook, projecting from the cylindrical head toward the distal end, receiving a locking pin 218 , although other latching members, such as a projection with aperture for receiving a locking pin may also be suitable, as noted above.
  • the second dilator tube has an inner lumen 194 with a distal opening 196 , and a proximal opening 198 .
  • the cylindrical head includes a first radial aperture 200 for receiving the locking pin 216 , and a second longitudinal aperture 201 for receiving the distally projecting latching member of the cylindrical head of the first or inner dilator tube.
  • the dilation introducer includes at least one additional dilator tube, such as a still shorter third or outer dilator tube 202 having a distal end 204 with a tapered tip 206 , and a proximal end 208 to which a handle 210 is connected at its head end 212 .
  • the head end of the handle includes a radial aperture 214 for receiving the locking pin 218 , and a longitudinal aperture 215 for receiving the distally projecting latching member of the cylindrical head of the second or intermediate dilator tube.
  • the first locking pin 216 is substantially the same as the second locking pin 218 .
  • the third dilator tube has an inner lumen 219 with proximal and distal openings.
  • a tubular bone drill or tap can be inserted through the first or inner dilator tube, and the tubular bone drill or tap can be threaded over a guide wire or K wire to contact the surface of the vertebra or bone to be treated, as described above.
  • the invention provides for a third presently preferred embodiment of a dilation introducer 220 , shown in a locked assembled configuration in FIG. 13 , and shown in an unlocked, collapsed configuration in FIG. 14 .
  • the dilation introducer includes a first or inner dilator tube 222 having a distal end 224 with a tapered, beveled tip 226 , and a proximal end 228 with a cylindrical head 230 .
  • the means for removably connecting the first and second dilator tubes together in a locked configuration includes a pair of opposing bayonet pins 232 extending from the proximal end of the first dilator tube.
  • the first dilator tube has an inner lumen 234 with a distal opening 236 and a proximal opening 238 .
  • the dilation introducer includes a shorter second or intermediate dilator tube 242 having a distal end 244 with a tapered, beveled tip 246 , and a proximal end 248 with a cylindrical head 250 .
  • a means for removably connecting the second and third dilator tubes together in a locked configuration includes a pair of opposing bayonet pins 252 .
  • the second dilator tube has an inner lumen 254 with a distal opening 256 and a proximal opening 258 , and as part of the means for removably connecting the second and third dilator tubes together, interior opposing bayonet slots 260 for receiving the pair of opposing bayonet pins of the first or inner dilator tube.
  • the dilation introducer includes at least one additional dilator tube, such as a still shorter third or outer dilator tube 262 having a distal end 264 with a tapered tip 266 , and a proximal end 268 having a pair of opposing handles 270 .
  • the third dilator tube has an inner lumen 271 , with proximal and distal openings.
  • a plastic sleeve 272 is slidably disposed over the shaft of the third or outer dilator tube, and the plastic sleeve preferably has a distal tapered, beveled end 274 .
  • a proximal sleeve ring 276 may also be slidably disposed over the shaft of the third or outer dilator tube between the plastic sleeve 272 and the opposing handles.
  • the tapered tips of the dilator tubes and plastic sleeve are beveled or angled at a common angle with respect to the longitudinal axis of the dilation introducer, so that the beveled edges of the tapered tips of the dilator tubes and plastic sleeve can be aligned together generally parallel to the surface of the soft tissue to be dilated, so that the bore and dilation passage of the dilation introducer may be aligned at a predetermined desired angle with respect to the soft tissue to be dilated and the bone tissue to be treated.
  • the third dilator tube includes interior opposing bayonet slots 278 for receiving the pair of opposing bayonet pins of the second or intermediate dilator tube.
  • a tubular bone drill or tap can be inserted through the first or inner dilator tube, and the tubular bone drill or tap can be threaded over a guide wire or K wire to contact the surface of the vertebra or bone to be treated, as described above.
  • the invention provides for a fourth embodiment of a dilation introducer 280 shown in a locked assembled configuration in FIG. 19 , and shown in an unlocked, collapsed configuration in FIG. 20 .
  • the dilation introducer includes a first or inner dilator tube 282 having a distal end 284 with a tapered tip 286 , and a proximal end 288 having a generally spherical handle or head 290 .
  • the proximal end of the first dilator tube near the handle includes a bayonet pin 292 .
  • the first dilator tube has an inner lumen 294 with a distal opening 296 , and a proximal opening 298 .
  • the dilation introducer includes a shorter second or intermediate dilator tube 302 having a distal end 304 with a tapered tip 306 , and a proximal end 308 having a generally cylindrical head 310 and a pair of opposing handles 312 .
  • the second dilator tube has an inner lumen 314 with a distal opening 316 and a proximal opening 318 .
  • the proximal end of the second dilator tube includes a bayonet slot 320 formed in the cylindrical head for receiving the bayonet pin of the first or inner dilator tube.
  • the dilation introducer includes at least one additional dilator tube, such as a still shorter third or outer dilator tube 322 , currently preferably formed of plastic, having a distal end 324 with a tapered tip 326 , and a proximal end 328 with a generally cylindrical head end or handle 330 .
  • the third dilator tube has an inner lumen 332 , with proximal and distal openings.
  • a tubular bone drill or tap can be inserted through the first or inner dilator tube, and the tubular bone drill or tap can be threaded over a guide wire or K wire to contact the surface of the vertebra or bone to be treated, as described above.
  • a surgical method for spinal fusion utilizing the dilation introducer apparatus and a bone fixation device such as a bone fixation device available under the trade name BONE-LOK from Triage Medical, Inc. of Irvine, Calif., is described.
  • a bone fixation device available under the trade name BONE-LOK from Triage Medical, Inc. of Irvine, Calif.
  • Other types of bone screws or fixation devices may also be suitable.
  • the method of the invention involves dilating a patient's soft tissue down to bone tissue to be treated in orthopedic surgery, and necessarily entails an incision and fluoroscopy to locate an entry point on the bone tissue to be treated.
  • An entry point is located on the bone tissue to be treated, and the tip of a guide wire or K-wire 151 is placed at the entry point on the bone tissue to be treated shown in FIG. 25 , and driven into the soft tissue of the patient to the target point of the inferior articular facet.
  • a vertical midline incision to a desired depth, such as approximately 17 mm, is made in the skin and fascia of the patient, using the entry point as the middle of the incision.
  • a first dilator tube of the dilation introducer is then passed over the guide wire until the tip of the dilation introducer reaches the target point of the bone.
  • the guide wire is then driven into the facet joint and into the pedicle of the patient, with verification of the trajectory and depth by fluoroscopy.
  • the second dilator tube of the dilation introducer is then released and passed over the first dilator tube to allow it to progress to the bone, allowing removal of the first dilator tube. This is repeated for the remaining, progressively wider telescoping dilator tubes, to progressively expand the patient's soft tissue down to the entry point on the bone tissue to be treated, and leaving an outer dilator tube port in place.
  • a depth gauge is then used to verify that the appropriate depth has been reached.
  • a pre-drill is advanced to the desired location, which is then also verified by fluoroscopy.
  • a cortex drill is advanced until its positive stop engages, and the distal tip of a tap is driven into the bone until it reaches the appropriate depth, which is then also verified by fluoroscopy.
  • the drill can be connected through an AO style quick connect, or a Jacobs chuck, as long as they are fully cannulated, to a ratcheting handle which is also preferably cannulated.
  • a bone fixation device is then driven into the bone until it reaches the appropriate depth, which is then also verified by fluoroscopy.
  • the bone fixation device is compressed to achieve appropriate stabilization, which is then also verified by fluoroscopy. Once compression of the bone fixation device has been achieved, the pull pin is removed, the guide wire is removed, and the remaining outer dilator tube port is removed, and the incision can be closed normally.
  • a guide wire or K wire assembly 340 for use with the telescoping dilation introducer of the invention includes an elongated, generally cylindrical first section 342 and an elongated, tubular second section 344 that is adapted to receive the first section.
  • the first section includes a proximal enlarged head or stop portion 346 , and a relatively narrow elongated body portion 348 .
  • the elongated body portion is preferably formed with a proximal section 350 having a relatively larger diameter to provide relatively greater strength, rigidity and torquability for manipulation of the guide wire, and a relatively narrower diameter main section 352 connected to the proximal section, and a pointed distal tip 354 at the distal end 358 of the main section.
  • the elongated tubular second section has a relatively larger diameter than the main section and an internal bore slightly larger in diameter than the main section for receiving the main section, as is illustrated in FIG. 28 .
  • the tubular second section advantageously also includes a frustoconical distal tip 362 with a narrowed portion 364 at the distal end 366 of the tubular distal section, and presenting an enlarged flat shoulder 368 at the proximal end of the frustoconical distal tip, so that when the guide wire assembly is assembled as shown in FIG.
  • the elongated main section is received in the internal bore of the elongated tubular section, and the proximal section of the elongated body portion of the elongated generally cylindrical section is seated against said proximal end of said elongated tubular section, the pointed distal tip extends out of said frustoconical distal tip of said elongated tubular section so that the assembly presents a pointed distal end, with a proximal shoulder against which a telescoping dilation introducer can be pushed for operation of the telescoping dilation introducer.
  • the elongated generally cylindrical first section thus adds a sharp point to the relatively blunt distal end of the elongated tubular second section, allowing the guide wire assembly to be inserted through soft tissue for placement in a soft tissue target of interest, such as an organ. Since the soft tissue present no hard surface against which the telescoping dilation introducer can be pushed, after the sharp point of the guide wire is placed in the desired location in the soft tissue, the first section can be removed from the second section, leaving the blunt distal end in place at the desired location in the soft tissue, and the telescoping dilation introducer can be placed over the second section and pressed against the shoulder of the blunt distal end for operation of the telescoping dilation introducer.
  • the outer dilator tube 400 includes a parallel guide insert 402 , shown in FIG. 31 .
  • the outer dilator tube has a distal end 404 with a tapered tip 406 , and a proximal portion 408 to which a handle 410 is connected at the extreme proximal or head end 412 of the outer dilator tube.
  • the head end of the outer dilator tube includes a radial aperture 414 for receiving the locking pin 416 , and a longitudinal aperture 418 for receiving a distally projecting latching member 420 of the cylindrical head 422 of the parallel guide insert.
  • the outer dilator tube has an inner bore 424 with proximal and distal openings.
  • the parallel guide insert includes a main cylindrical shaft 425 connected at a proximal end 426 to the cylindrical head of the parallel guide insert.
  • the parallel guide insert includes a plurality of longitudinal bores 428 extending the length of the parallel guide insert from the distal end 430 , with distal openings visible in FIG. 31 , to proximal openings (not shown) in the cylindrical head of the parallel guide insert.
  • a single guide wire or K wire or other device may be passed through one or more of the bores of the parallel guide insert, or multiple guide wires or K wires or other devices may be passed through a plurality of the bores simultaneously, as desired.
  • the parallel guide insert may be provided without a latching member, in order to allow the parallel guide member to be rotated freely to allow alignment of the desired locations of the guide wires through the holes in the parallel guide insert.
  • the outer dilator tube 440 includes a parallel guide insert 442 , shown in FIG. 33 .
  • the outer dilator tube has a distal end 444 with an angled tip 446 , and a proximal end 448 to which a handle 450 is connected at the extreme proximal or head end 452 of the outer dilator tube.
  • the head end of the outer dilator tube includes a radial aperture 454 for receiving the locking pin 456 , and a longitudinal aperture 458 for receiving a distally projecting latching member 460 of the cylindrical head 462 of the parallel guide insert.
  • the outer dilator tube has an inner bore 464 with proximal and distal openings.
  • the parallel guide insert includes a main cylindrical shaft 465 connected at a proximal end 466 to the cylindrical head of the parallel guide insert.
  • the parallel guide insert includes a plurality of longitudinal bores 468 extending the length of the parallel guide insert from the angled distal end 470 , with distal openings visible in FIG. 33 , to proximal openings (not shown) in the cylindrical head of the parallel guide insert.
  • the angled tips of the outer dilator tube and the parallel guide insert are beveled or angled at a common angle with respect to the longitudinal axis of the dilation introducer, so that the angled tips of the outer dilator tube and the parallel guide insert can be aligned together generally parallel to the surface of the soft tissue to be dilated, with the bore and dilation passage of the dilation introducer aligned at a predetermined desired angle with respect to the soft tissue to be dilated and the bone tissue to be treated.
  • a single guide wire or K wire or other device may be passed through one or more of the bores of the parallel guide insert, or multiple guide wires or K wires or other devices may be passed through a plurality of the bores simultaneously, as desired.
  • the distal tip 480 of an outer dilator tube 482 may be angled or beveled, and may include a plurality of spikes 484 to provide for increased traction of the tip of the outer dilator tube on bone tissue.
  • the spikes may be formed of radiopaque material, such as gold, platinum, tantalum or the like, for use with fluoroscopy.
  • a parallel guide 486 disposed in the outer dilator tube has a distal tip 488 that may optionally also be provided with a plurality of embedded spikes 490 for increased traction on bone tissue.
  • the spikes of the outer dilator tube and parallel guide may formed with a rounded shape so as to deflect soft tissue during dilation, and to provide increased traction with bone upon completion of the insertion of the dilator.
  • the invention provides for a fifth presently preferred embodiment of a dilation introducer 500 , which is similar to the embodiment illustrated in FIGS. 8-12 , and which is shown in an unlocked configuration in FIG. 36 .
  • the dilation introducer includes a first or inner dilator tube 502 having distal end (not shown) and a proximal end 504 with a cylindrical head 506 .
  • the means for removably connecting the first and second dilator tubes together in a locked configuration includes a first latching member 508 , having a shaft 510 and a latching end 512 , such as a hook, projecting from the cylindrical head toward the distal end, and connected to a locking button 514 , which extends transversely out through a side aperture 516 in the cylindrical head.
  • the locking button includes a shaft 518 and an enlarged head 520 connected to the shaft, and the locking button is biased outwardly from the cylindrical head by a spring 522 .
  • the latching member is received in an upper aperture 524 of the adjacent cylindrical head of a second or intermediate dilator tube 526 , having a side opening latching chamber 528 for retaining the latching end of the latching member when the locking button is biased outwardly by its spring, to lock the cylindrical heads of the first and second dilator tubes together.
  • the cylindrical heads of the first and second dilator tubes can be unlocked and separated by manually depressing the locking button to move the latching member inwardly and the latching end of the latching member inwardly out of the side opening latching chamber.
  • the first dilator tube is essentially the same as the first dilator tube of the embodiment of FIGS. 8-12 .
  • the second or intermediate dilator tube 526 of the dilation introducer has a distal end (not shown) and a proximal end 530 with a cylindrical head 532 .
  • the means for removably connecting the second and third dilator tubes together in a locked configuration includes a second latching member 534 , having a shaft 536 and a latching end 538 , such as a hook, projecting from the cylindrical head toward the distal end, and connected to a second locking button 540 , which extends transversely out through a side aperture 542 in the cylindrical head.
  • the locking button includes a shaft 544 and an enlarged head 546 connected to the shaft, and the locking button is biased outwardly from the cylindrical head by a spring 548 .
  • the latching member is received in an upper aperture 550 of the adjacent cylindrical head of a third or second intermediate dilator tube 552 , having a side opening latching chamber 554 for retaining the latching end of the latching member when the locking button is biased outwardly by its spring, to lock the cylindrical heads of the second and third dilator tubes together.
  • the cylindrical heads of the second and third dilator tubes can be unlocked and separated by manually depressing the second locking button to move the latching member inwardly and the latching end of the latching member inwardly out of the side opening latching chamber.
  • the second dilator tube is essentially the same as the second dilator tube of the embodiment of FIGS. 8-12 .
  • the third, or second intermediate, dilator tube 552 of the dilation introducer has a distal end (not shown) and a proximal end 556 with a cylindrical head 558 .
  • the means for removably connecting the third dilator tube and the outer dilator tube 560 together in a locked configuration includes a third latching member 562 , having a shaft 564 and a latching end 566 , such as a hook, projecting from the cylindrical head toward the distal end, and connected to a third locking button 568 , which extends transversely out through a side aperture 570 in the cylindrical head.
  • the third locking button includes a shaft 572 and an enlarged head 574 connected to the shaft, and the third locking button is biased outwardly from the cylindrical head by a spring 576 .
  • the latching member is received in an upper aperture 578 of the adjacent cylindrical head 580 of the outer dilator tube, having a side opening latching chamber 582 for retaining the latching end of the latching member when the locking button is biased outwardly by its spring, to lock the cylindrical heads of the third and outer dilator tubes together.
  • the cylindrical heads of the third and outer dilator tubes can be unlocked and separated by manually depressing the third locking button to move the latching member inwardly and the latching end of the latching member inwardly out of the side opening latching chamber.
  • the third dilator tube is essentially the same as the second dilator tube of the embodiment of FIGS. 8-12 .
  • the outer dilator tube includes a distal end (not shown) and a proximal end 584 to which a handle 586 is connected at its cylindrical head end.
  • the head end of the handle preferably includes a plurality of the upper apertures 578 connected to corresponding side opening latching apertures 582 for receiving the latching member of the adjacent dilator tube cylindrical head, as is illustrated in FIG. 40 .
  • the outer dilator tube is essentially the same as the outer dilator tube of the embodiment of FIGS. 8-12 .
  • the side opening latching chambers of the cylindrical heads of the dilator tubes may be closed so as to form covered latching chambers 590 a, b, c for the latching members.
  • the variation shown in FIGS. 38 and 39 is essentially the same as in FIGS. 36 and 37 .
  • an outer dilation tube 600 may be provided with a light emitter 602 , such as one or more light emitting diodes (LEDs) or the end of a fiber optic, connected to or embedded in the tubular shaft 604 of the outer dilation tube, and preferably near the distal end 606 of the tubular shaft.
  • the light emitter may be an LED embedded in the wall 608 of the tubular shaft, with the LED directed to illuminate the interior, exterior, or distal edge of the tubular shaft of the outer dilation tube. As is shown in FIG.
  • one or more elongated energy conducting members 610 may be embedded in the tubular shaft, for conducting electricity or light to the light emitter.
  • the handle 612 of the outer dilator tube preferably contains one or more batteries 614 connected to a switch 616 which is in turn connected to power the light emitter.
  • the handle may be provided with a battery or batteries, which may be disposable, a switch, resistor and other associated electronics, so that the handle is disposable, or alternatively the handle may be provided with a connector for connection to an external power source.
  • the switch is a thumb switch conveniently located on the handle adjacent to the cylindrical head 618 of the outer dilation tube.
  • the handle, cylindrical head, and tubular shaft of the outer dilation tube preferably includes one or more channels 620 for the electrical wires connecting the one or more batteries to the switch and to the light emitter.
  • a light source 622 such as one or more LEDs providing light to be conducted through the one or more fiber optics may be placed adjacent to the switch in the handle, with the one or more fiber optics extending through the wall of the tubular shaft of the outer dilator tube.
  • the one or more elongated energy conducting members such as one or more wires or one or more fiber optics, may be disposed on the outer surface of the tubular shaft of the outer dilation tube.
  • the tubular shaft of the outer dilation tube may be formed with a groove 620 running longitudinally on the exterior surface of the tubular shaft, parallel to the longitudinal axis of the outer dilation tube, to accommodate one or more wires or one or more fiber optics.
  • the one or more elongated energy conducting members may be located on the inside of the dilator tube, or may extend through the wall of the dilator tube.
  • the present invention also provides for a telescoping expander sleeve 630 that is adapted to be slidably disposed over the shaft of an outer dilator tube of any of the foregoing embodiments for expanding the patient's soft tissue down to the entry point on the bone tissue to be treated, while leaving the outer dilator tube in place, or allowing for replacement of the outer dilator tube with other equipment for treatment of the bone tissue.
  • the tubular proximal portion may optionally be provided with a handle.
  • the expander sleeve may be pre-assembled in combination with one or more of the dilation introducers, adapted to be ready for use.
  • the telescoping expander sleeve has a first or inner generally tubular section 632 , having a tubular proximal portion 634 with an enlarged proximal head 636 , and a distal portion 638 with at least two substantially identical opposing active spreader arms 640 (one of which is not visible in FIGS. 44-46 ) connected at one end to the tubular proximal portion and moveable radially at their distal tips 642 .
  • the distal tips of the active spreader arms preferably have beveled edges 644 to deflect soft tissue during insertion of the telescoping expander sleeve.
  • a second or outer generally tubular section 646 is slidably disposed over the first or inner generally tubular section, and includes a tubular proximal portion 648 and a distal portion 650 with at least two substantial identical opposing passive spreader flaps 652 interposed between the active spreader arms, hingedly connected to the tubular proximal portion at proximal ends 654 , and moveable radially at their distal tips 656 .
  • the distal tips of the passive spreader flaps preferably also have beveled edges to deflect soft tissue during insertion of the telescoping expander sleeve.
  • the distal tips of the passive spreader flaps when placed together in an unexpanded configuration have a generally circular configuration, so that the distal tips of two passive spreader flaps, for example, have a semi-circular configuration.
  • the passive spreader flaps taper progressively toward their narrowed proximal ends connected to the tubular proximal portion of the outer tubular section.
  • the passive spreader flaps are connected to the tubular proximal portion of the outer generally tubular section by rings 656 passing through apertures 658 and 660 in the adjacent ends of the tubular proximal portion and the passive spreader flaps, respectively.
  • the active spreader arms are slidably interposed between and engage the passive spreader flaps, so that as the telescoping expander sleeve telescopes from an extended, unexpanded configuration to a collapsed, expanded configuration, as shown in FIG. 44 , the active spreader arms slide from the narrow proximal ends of the passive spreader flaps to the wider distal ends of the passive spreader flaps to spread the distal ends of the passive spreader flaps apart, which also forces the distal ends of the active spreader arms apart, as shown in FIG. 46 .
  • the distal ends of the active spreader arms are slidably connected to slots 662 extending along the inner edges 664 of the passive spreader flaps by loops or rings 666 , such as loops of nylon filament or metal rings, for example, which pass through apertures 668 in the distal ends of the active spreader arms.
  • Telescoping of expander sleeve from a collapsed, expanded configuration to an extended, unexpanded configuration thus slides the distal ends of the active spreader arms of the inner tubular section from the wide distal ends of the passive spreader flaps along the inner edges of the passive spreader flaps to the narrowed proximal ends of the passive spreader flaps, to bring the passive spreader flaps together.
  • the purpose of the active spreader arms and passive spreader flaps is to facilitate the creating of a larger working area adjacent to bone or bone tissues being treated.
  • the spreader arms and flaps may optionally be covered by an expandable material, such as latex, for example, with a central through hole permitting operation of the device, to cover the spreader arms and flaps to prevent tissues from being pressed into cavities of the telescoping expander sleeve.
  • the components of the dilation introducer may be formed from plastic, stainless steel, or similar materials or combinations thereof, that can be readily sterilized and packaged ready for use, after which the dilation introducer may be disposed of or resterilized for subsequent use, as desired.
  • the dilator tubes may be radioluscent, with radiopaque markers located on the tips of one or more of the dilator tubes.
  • the tip of the first dilator may also be scored, grooved, or otherwise be provided with a rough surface, to prevent migration.
  • the dilation introducer may also have curved or otherwise non-linear dilator tubes, and the dilation introducer may also have a non-cylindrical shape, such as an oval shape, for example, to allow the dilation introducer to be inserted around objects or a patient's organs.
  • one or more devices can be inserted through the same dilation introducer, and that the dilation introducer can be repositioned within the same incision for fixation of multiple devices.
  • fiber optic devices may be inserted through or integrated with the dilation introducer for visual inspection of the target area. While particular locking features have been described for the different embodiments of the dilation introducer, any combination of locking features or alternate locking features may be utilized.
  • the outer dilator tube may not be locked, and a handle on the outer dilator tube may simply be used as a stop.
  • the dilation introducer of the invention can also be useful in dilation of soft tissue for percutaneous, minimally invasive surgical procedures such as nephrostomy, neurosurgery, heart valve repair or replacement, gastrointestinal surgery such as for gall bladder or gall stone surgery, hernia removal, transjugular intrahepatic portal-systemic shunt (TIPS) procedures for treatment of the liver, and the like.
  • percutaneous, minimally invasive surgical procedures such as nephrostomy, neurosurgery, heart valve repair or replacement
  • gastrointestinal surgery such as for gall bladder or gall stone surgery
  • hernia removal such as for gall bladder or gall stone surgery
  • TIPS transjugular intrahepatic portal-systemic shunt

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Microbiology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Evolutionary Biology (AREA)
  • Theoretical Computer Science (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Analytical Chemistry (AREA)
  • Medical Informatics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Endocrinology (AREA)
  • Oncology (AREA)
  • Neurology (AREA)
  • Diabetes (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)

Abstract

The dilation introducer has a locked assembled configuration for placement of the dilation introducer against a patient's tissue to be treated, and an unlocked, collapsed configuration for dilating the patient's soft tissue down to tissue to be treated. Dilator tubes are successively released and advanced to progressively expand the patient's soft tissue down to the bone tissue to be treated. The dilator tubes and a guide insert may include spikes for engaging bone tissue. The dilation introducer may include a light emitter disposed in a dilator tube. A telescoping expander sleeve is also provided.

Description

    CROSS-REFERENCES TO RELATED APPLICATIONS
  • This is a continuation-in-part of Ser. No. 10/911,215, filed Aug. 3, 2004.
    • BACKGROUND OF THE INVENTION
  • 1. Field of the Invention
  • This invention relates to bone fixation devices, and more particularly relates to a dilation introducer for introducing a bone fixation device for orthopedic surgery, such as for vertebral fusion.
  • 2. General Background and State of the Art
  • Fusion of two adjacent vertebrae is a common surgical treatment for back injuries due to damage or defects in a spinal disc between two adjacent vertebrae, such as conditions due to a herniated disc or disc degeneration. The entire disc may be removed by a discectomy procedure, and may be replaced with bone or a bone substitute and/or cage in order to prevent collapse of the disc space between the adjacent vertebrae. Early techniques for stabilizing the adjacent vertebrae included application of a plate or a rod in conjunction with screws across the adjacent vertebrae, after which the adjacent vertebrae would eventually fuse together. However, such techniques commonly required prolonged periods of recovery from the extensive surgery involved, and it would be desirable to provide an improved apparatus and method for providing a minimally invasive procedure that will result in less trauma and improvement in patient recovery.
  • Bone fixation devices are known that are useful for connecting two or more bone segments for the healing of broken bones, typically including an elongate pin with a distal anchor and a proximal anchor movable on the pin to accommodate different bone dimensions, and to permit tensioning of the bone segments together. The surgical procedure of attaching two or more parts of a bone with a pin-like device commonly requires an initial incision into the tissue down to the bone, and the drilling of a hole through the bone parts to be joined. Such bone fixation devices can be useful for fusion of vertebrae together, because such a bone fixation device can be used to join adjacent bone segments through a single percutaneous incision or puncture, without the need to expose any other side of the bone segments to be joined. In either type of procedure, there is substantial trauma to the surrounding tissue if a large incision is required. Thus, it would be desirable to provide a minimally invasive dilation introducer to allow the penetration and spreading of soft tissues down to vertebrae to be fused, for use of such a bone fixation device to join adjacent vertebrae, and to allow for more easily performing the delicate maneuvering of drilling adjacent vertebrae and application of one or more bone fixation devices to join the vertebrae to be fused. The present invention satisfies these and other needs.
    • INVENTION SUMMARY
  • Briefly, and in general terms, the invention provides for a telescoping dilation introducer for orthopedic surgery, the dilation introducer having a locked assembled configuration for initial placement of the dilation introducer against a patient's tissue to be treated, and an unlocked, collapsed configuration for dilating the patient's soft surrounding tissue to a desired degree of dilation to permit minimally invasive surgical procedures on the patient's tissue. As the telescoping dilation introducer is inserted, each individual dilator tube is successively released and advanced to progressively expand the patient's soft tissue down to the tissue to be treated. In a particularly useful aspect of the invention, the tissue to be treated is bone tissue which must be prepared prior to attachment of adjacent bone section in a fusion process. While there are many applications of the dilation introducer of the invention, the invention is particularly applicable to fusion of bones in orthopedic surgery using minimally invasive technique, and will be described herein in particular applications of those procedures. The invention also concerns a minimally invasive procedure utilizing the telescoping dilation introducer to insert a bone fixation device into a patient's spine for posterior spine fusion. While posterior spine fusion currently takes up to two hours to complete, and requires a six inch incision, with the apparatus and method of the invention, comparable surgery can be completed in less than thirty minutes, with a dilation port 13 mm or less in diameter, thus lowering the chance of damage to the surrounding soft tissue.
  • A telescoping dilation introducer is typically operated by pressing the introducer against a relatively hard surface, such as bone tissue being treated. The present invention provides for a guide wire assembly when such a telescoping dilation introducer is to used in treatment of soft tissue, such as an organ, to provide a surface against which the telescoping dilation introducer can be pushed during operation of the telescoping dilation introducer. In a presently preferred embodiment, a guide wire or K wire assembly is provided for use with a telescoping dilation introducer according to the invention. The guide wire assembly includes an elongated generally cylindrical first section, and an elongated tubular second section that receives the first section. The elongated generally cylindrical first section includes a proximal enlarged head or stop portion, and an elongated body portion with a proximal section and a relatively narrower diameter main section connected to the proximal section, and a pointed distal tip at the distal end of the narrow main section. The second section of the guide wire assembly includes an elongated tubular body with an internal bore adapted to receive the narrow main section, as is illustrated in FIG. 28. The tubular second section advantageously includes a frustoconical distal tip with a narrowed portion at the distal end and an enlarged flat shoulder at the proximal end of the frustoconical distal tip. When the guide wire assembly is assembled, the assembly presents a pointed distal end with a proximal shoulder against which a telescoping dilation introducer can be pushed for operation of the telescoping dilation introducer. The main section thus adds a sharp point to the relatively blunt distal end of the tubular distal section, allowing the guide wire assembly to be inserted through soft tissue for placement in a soft tissue target of interest, such as an organ, and the first section can then be removed to allow a telescoping dilation introducer to be placed over the second section and pressed against the shoulder of the blunt distal end for operation of the telescoping dilation introducer. After the sharp point of the guide wire is placed in the desired location in the soft tissue, the first section can be removed from the second section, leaving the blunt distal end in place at the desired location in the soft tissue, and the telescoping dilation introducer can be placed over the second section and pressed against the shoulder of the blunt distal end for operation of the telescoping dilation introducer.
  • In one presently preferred embodiment, the present invention provides for an improvement in a dilation introducer for orthopedic surgery, in which the dilation introducer includes one or more dilator tubes having a distal end and a proximal end, and the distal end of the one or more dilator tubes including a plurality of spikes for engaging bone tissue. In one presently preferred aspect, the spikes may be formed of radiopaque material, for fluoroscopic imaging of the positioning of the one or more dilator tubes, and the spikes may be formed with a rounded shape so as to deflect soft tissue.
  • In another presently preferred aspect, the dilation introducer includes a parallel guide insert adapted to be received in the one or more dilator tubes. The parallel guide insert includes a main cylindrical shaft having a proximal end connected to a cylindrical head, and a plurality of longitudinal bores extending the length of the parallel guide insert through the main cylindrical shaft and cylindrical head. The distal tip of the parallel guide insert may be provided with a plurality of spikes for engaging bone tissue. The spikes of the parallel guide insert may be formed of radiopaque material, and may be formed with a rounded shape so as to deflect soft tissue.
  • In another presently preferred embodiment, the present invention concerns a dilation introducer for orthopedic surgery having a locked assembled configuration for initial placement of the dilation introducer against a patient's bone tissue to be treated, and an unlocked, collapsed configuration dilating the patient's soft tissue down to the bone tissue to be treated to a desired degree of dilation to permit minimally invasive surgical procedures on the patient's bone tissue to be treated. The dilation introducer includes a first dilator tube having a distal end with a tapered tip and a proximal end with a cylindrical head, and a second dilator tube having a distal end with a tapered tip and a proximal end with a cylindrical head, and an inner lumen with a distal opening and a proximal opening. The first dilator tube is removably received in the second dilator tube for slidable telescoping movement within the second dilator tube. Means are provided for removably connecting the first and second dilator tubes together in a locked configuration. The means for removably connecting the first and second dilator tubes includes a first latching member disposed in the cylindrical head of the first dilator tube. The first latching member has a locking button connected transversely to a shaft with a latching end projecting from the cylindrical head of the first dilator tube toward the distal end of the first dilator tube, with the locking button extending transversely from the shaft through a side aperture in the cylindrical head of the first dilator tube. The locking button is biased outwardly from the cylindrical head, such as by a spring, and the first latching member is received in an upper aperture of the cylindrical head of an adjacent second dilator tube. The upper aperture of the cylindrical head of the second dilator tube includes a latching chamber for retaining the latching end of the latching member when the locking button is biased outwardly, to lock the cylindrical heads of the first and second dilator tubes together. The locking button is moveable inwardly to move the latching member inwardly and to move the latching end of the latching member inwardly out of the latching chamber, to unlock the first and second dilator tubes.
  • The dilation introducer may include one or more additional dilator tubes, with the second dilator tube being removably received in the one or more additional dilator tubes for slidable telescoping movement within the one or more additional dilator tubes. The one or more additional dilator tubes likewise have a distal end and a proximal end with a cylindrical head, an inner lumen with a distal opening and a proximal opening, and the distal end having a tapered tip. The second dilator tube and the one or more additional dilator tubes having an unlocked configuration in which the one or more additional dilator tubes may slidably telescope over the second dilator tube to dilate the patient's soft tissue at the distal end of the dilation introducer. Means are provided for removably connecting the second dilator tube and the one or more additional dilator tubes together in a locked configuration. The means for removably connecting the second dilator tube and the one or more additional dilator tubes include a second latching member disposed in the cylindrical head of the second dilator tube. The second latching member has a locking button connected transversely to a shaft with a latching end projecting from the cylindrical head of the second dilator tube toward the distal end of the second dilator tube, and the locking button extends transversely from the shaft through a side aperture in the cylindrical head of the second dilator tube. The locking button is biased outwardly from the cylindrical head, such as by a spring, and the second latching member is received in an upper aperture of the cylindrical head of the additional dilator tube to be connected. The upper aperture of the cylindrical head of the additional dilator tubes include a latching chamber for retaining the latching end of the second latching member when the locking button is biased outwardly, to lock the cylindrical heads of the second and additional dilator tube together, and the locking button is moveable inwardly to move the second latching member inwardly and the latching end of the second latching member inwardly out of the latching chamber.
  • In a presently preferred aspect, the additional dilator tube comprises a handle connected to the proximal end of the additional dilator tube, and the cylindrical head of the additional dilator tube includes a plurality of the upper apertures, each including a latching chamber for receiving the second latching member.
  • In another presently preferred embodiment, the present invention provides for an improvement in a dilation introducer for orthopedic surgery, in which the dilation introducer includes a dilator tube having a tubular shaft, a distal end and a proximal end, an inner lumen with a distal opening and a proximal opening, and a light emitter disposed in the dilator tube. In one aspect, the light emitter may be a light emitting diode, and the light emitting diode may be embedded in the tubular shaft of the dilator tube. In another aspect, the light emitter may include a fiber optic, and the fiber optic may be embedded in the tubular shaft of the dilator tube.
  • In a presently preferred aspect, the dilator tube includes a handle and a switch for controlling the light emitter, and at least one battery is disposed in the handle and is connected to the switch to power the light emitter. Where the light emitter includes one or more fiber optics, the light emitter includes a light source providing light conducted to the one or more fiber optics. The light emitter may include one or more elongated energy conducting members disposed on an outer surface of the tubular shaft of the dilator tube, and the one or more elongated energy conducting members may be disposed in a groove on the exterior surface of the tubular shaft. Alternatively, the one or more elongated energy conducting members may be located on the inside of the dilator tube, or may extend through the wall of the dilator tube.
  • The present invention also provides for a telescoping expander sleeve adapted to be slidably disposed over a shaft of a dilator tube for dilating a patient's soft tissue down to a bone tissue to be treated to a desired degree of dilation to permit minimally invasive surgical procedures on the patient's bone tissue. The telescoping expander sleeve is moveable between an extended, unexpanded configuration and a collapsed, expanded configuration. The telescoping expander sleeve includes a first generally tubular section having a tubular proximal portion and a distal portion. The tubular proximal portion has an enlarged proximal head, and the distal portion includes two or more active spreader arms each having a proximal end and a distal tip. The tubular proximal portion may optionally be provided with a handle. The two or more active spreader arms are connected at their proximal ends to the tubular proximal portion, and the distal tips of the two or more active spreader arms are moveable radially between an unexpanded configuration and an expanded configuration.
  • The telescoping expander sleeve also includes a second generally tubular section slidably disposed over the first generally tubular section. The second generally tubular section includes a tubular proximal portion and a distal portion including two or more passive spreader flaps each having a narrow proximal end and a wide distal tip. The proximal ends of the two or more passive spreader flaps are hingedly connected to the tubular proximal portion, and the distal tips of the two or more passive spreader flaps are moveable radially between an unexpanded configuration and an expanded configuration. The two or more active spreader arms slidably engage the two or more passive spreader flaps, so that as the telescoping expander sleeve telescopes from the extended, unexpanded configuration to the collapsed, expanded configuration, the two or more active spreader arms slide from the narrow proximal ends of the two or more passive spreader flaps to the wider distal ends of the passive spreader flaps to spread the distal ends of the two or more passive spreader flaps apart, and to spread the distal ends of the two or more active spreader arms apart.
  • In a presently preferred aspect, the distal tips of the two or more active spreader arms have beveled edges to deflect soft tissue during insertion of the telescoping expander sleeve, and the distal tips of the two or more passive spreader flaps have beveled edges to deflect soft tissue during insertion of the telescoping expander sleeve. The purpose of the active spreader arms and passive spreader flaps is to facilitate the creating of a larger working area adjacent to bone or bone tissues being treated. The spreader arms and flaps may optionally be covered by an expandable material, such as latex, for example, to prevent tissues from being pressed into cavities of the telescoping expander sleeve.
  • While the present invention is particularly useful for the purposes of orthopedic surgery, those skilled in the art will recognize that the invention can also be used for the treatment of a variety of internal organs or structures when it is desired to minimize the size of an opening in the patient's soft tissue and the resultant damage and trauma to tissue surrounding the operation site.
  • Other features and advantages of the present invention will become more apparent from the following detailed description of the preferred embodiments in conjunction with the accompanying drawings, which illustrate, by way of example, the operation of the invention.
    • BRIEF DESCRIPTION OF THE DRAWINGS
  • FIG. 1 is a plan view of a first embodiment of a dilation introducer in a locked configuration, according to the present invention.
  • FIG. 2 is a plan view of the dilation introducer of FIG. 1 shown in an unlocked, collapsed configuration.
  • FIG. 3 is a plan view of the first or inner dilator tube of the dilation introducer of FIG. 1.
  • FIG. 4 is a plan view of the second or intermediate dilator tube of the dilation introducer of FIG. 1.
  • FIG. 5 is a plan view of the third or outer dilator tube of the dilation introducer of FIG. 1.
  • FIG. 6A is a top plan view of the first locking clip of the dilation introducer of FIG. 1.
  • FIG. 6B is an elevational view of the first locking clip of the dilation introducer of FIG. 1.
  • FIG. 6C is a bottom plan view of the first locking clip of the dilation introducer of FIG. 1.
  • FIG. 7A is a top plan view of the second locking clip of the dilation introducer of FIG. 1.
  • FIG. 7B is an elevational view of the second locking clip of the dilation introducer of FIG. 1.
  • FIG. 8 is a perspective view of a second embodiment of a dilation introducer in a locked configuration, according to the present invention.
  • FIG. 9 is a perspective view of the dilation introducer of FIG. 8 shown in an unlocked, collapsed configuration.
  • FIG. 10 is a perspective view of the first or inner dilator tube of the dilation introducer of FIG. 8.
  • FIG. 11 is a perspective view of the second or intermediate dilator tube of the dilation introducer of FIG. 8.
  • FIG. 12 is a plan view of the third or outer dilator tube of the dilation introducer of FIG. 8.
  • FIG. 13 is a plan view of a third embodiment of a dilation introducer in a locked configuration, according to the present invention.
  • FIG. 14 is a plan view of the dilation introducer of FIG. 13 shown in an unlocked, collapsed configuration.
  • FIG. 15 is a plan view of the first or inner dilator tube of the dilation introducer of FIG. 13.
  • FIG. 16 is a plan view of the second or intermediate dilator tube of the dilation introducer of FIG. 13.
  • FIG. 17 is a plan view of the third or outer dilator tube of the dilation introducer of FIG. 13.
  • FIG. 18 is a plan view of the plastic sleeve of the dilation introducer of FIG. 13.
  • FIG. 19 is a plan view of a fourth embodiment of a dilation introducer in a locked configuration, according to the present invention.
  • FIG. 20 is a plan view of the dilation introducer of FIG. 19 shown in an unlocked, collapsed configuration.
  • FIG. 21 is a plan view of the first or inner dilator tube of the dilation introducer of FIG. 19.
  • FIG. 22 is a plan view of the second or intermediate dilator tube of the dilation introducer of FIG. 19.
  • FIG. 23 is a plan view of the third or outer dilator tube of the dilation introducer of FIG. 19.
  • FIG. 24 is a schematic diagram illustrating location of a starting point for insertion of a bone fixation device according to the method of the invention.
  • FIG. 25 is a schematic diagram of a lateral view illustrating location of a trajectory for insertion of a bone fixation device according to the method of the invention.
  • FIG. 26 is a schematic diagram of an anterior view illustrating location of a trajectory for insertion of a bone fixation device according to the method of the invention.
  • FIG. 27 is a plan view of a guide wire assembly for use with the various embodiments of the telescoping dilation introducer of the invention, shown disassembled.
  • FIG. 28 is a plan view of the guide wire assembly of FIG. 27, shown partially assembled.
  • FIG. 29 is a plan view of the guide wire assembly of FIG. 27, shown fully assembled.
  • FIG. 30 is a perspective view of a variation of the outer dilator tube of the embodiment of FIGS. 8-12, with a parallel guide.
  • FIG. 31 is a perspective view of the parallel guide from FIG. 30.
  • FIG. 32 is a perspective view of a variation of the outer dilator tube of the embodiment of FIGS. 8-12, with an angled tip and with a parallel guide.
  • FIG. 33 is a perspective view of the parallel guide with an angled tip from FIG. 32.
  • FIG. 34 is a perspective of another variation of the outer dilator tube of the embodiment of FIGS. 8-12, with an angled tip and spikes.
  • FIG. 35 is a perspective view of the outer dilator tube of FIG. 34, with a parallel guide with spikes.
  • FIG. 36 is a perspective view of a fifth embodiment of a dilation introducer in an unlocked configuration, according to the present invention.
  • FIG. 37 is a sectional view of a portion of the dilation introducer of FIG. 36.
  • FIG. 38 is a perspective view of a variation of the dilation introducer of FIG. 36, shown in a locked configuration, according to the present invention.
  • FIG. 39 is a sectional view of a portion of the dilation introducer of FIG. 36 taken along line 39-39 of FIG. 38.
  • FIG. 40 is a top perspective view of the head end of the handle of the dilation introducer of FIG. 36, showing multiple locking locations.
  • FIG. 41 is a schematic diagram of a variation of the dilation introducer of FIG. 36, with a light emitter and switch for the light emitter.
  • FIG. 42 is an enlarged view of the tip of the dilation introducer of FIG. 41.
  • FIG. 43 is a perspective view of another variation of the dilation introducer of FIG. 41, with an exterior groove for one or more elongated energy conducting members.
  • FIG. 44 is a side elevational view of a telescoping expander sleeve shown in an extended, unexpanded configuration.
  • FIG. 45 is a side elevational view of the telescoping expander sleeve of FIG. 44 shown in an intermediate partially collapsed, partially expanded configuration.
  • FIG. 46 is a side elevational view of the telescoping expander sleeve of FIG. 44 shown in a fully collapsed, fully expanded configuration.
    • DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
  • Referring to the drawings, which are provided for purposes of illustration and by way of example, the present invention provides for a telescoping dilation introducer for orthopedic surgery, the dilation introducer having a locked assembled configuration for initial placement of the dilation introducer against a patient's bone tissue to be treated, and an unlocked, collapsed configuration dilating the patient's soft tissue down to the bone tissue to be treated to a desired degree of dilation to permit minimally invasive surgical procedures on the patient's bone tissue to be treated.
  • While the invention will be described with specificity to a spinal fusion procedure, those skilled in the art will recognize that the apparatus and method of the art will recognize that the apparatus and method of the invention can also be advantageously used for procedures in which the dilation introducer can be brought up against other firm or solid structures in the body or introduced into the body to thereby gain the advantages of the invention for other minimally invasive procedures.
  • A dilation introducer 30 according to a first preferred embodiment is shown in a locked assembled configuration in FIG. 1, and shown in an unlocked, collapsed configuration in FIG. 2. Referring to FIG. 3, the dilation introducer includes a first or inner dilator tube 32 having a distal end 34 with a tapered tip 36, and a proximal end 38 with a head 40 including a pair of spaced part rings 42. The first dilator tube has an inner lumen 44 with a distal opening 46 and a proximal opening 48.
  • Referring to FIG. 4, the dilation introducer also includes a shorter second or intermediate dilator tube 52 having a distal end 54 with a tapered tip 56, and a proximal end 58 with a head 60 including a pair of spaced apart rings 62. The second dilator tube has an inner lumen 64 with a distal opening 66 and a proximal opening 68.
  • Referring to FIG. 5, in a presently preferred aspect, the dilation introducer also includes at least one additional dilator tube, such as a still shorter third or outer dilator tube 72 having a distal end 74 with a tapered tip 76, and a proximal end 78 with a handle 80. The third dilator tube has an inner lumen 82 with a distal opening 84 and a proximal opening 86.
  • Referring to FIGS. 6A, 6B and 6C, the means for removably connecting the first and second dilator tubes together in a locked configuration includes a first locking clip 88. As is shown in FIGS. 7A and 7B, a means for removably connecting the second and third dilator tubes together in a locked configuration may also be provided, and may include a second locking clip 90. The first locking clip includes a first portion 92 and a second portion 94, and a cross-piece or handle 96 having a first end 98 and a second end 100 connected at right angles between the first and second portions. The first portion includes pair of resilient arms 102 each having a proximal narrow neck portion 104 connected to the cross-piece, and a distal gripping portion 106 extending from the narrow neck portion. The resilient arms have an inner rounded surface 108 adapted to snap over the first dilator tube between the spaced apart rings of the first dilator tube. The second portion currently preferably includes a single arm 112 having a proximal narrow neck portion 114, and a distal gripping portion 116 extending from the narrow neck portion. The gripping portion has an inner rounded surface 118 adapted to fit over the outer surface of the second dilator tube between the spaced apart rings of the second dilator tube, to connect the first and second dilator tubes. Removing the first locking clip allows the second or intermediate dilator tube to slidably telescope over the first inner dilator tube to dilate tissue at the distal end of the dilation introducer.
  • The second locking clip includes a first portion 122 and a second portion 124, and a cross-piece or handle 126 having a first end 128 and a second end 130 connected between the first portion and the second portion at right angles. The first portion includes a pair of resilient arms 132 each having a proximal narrow neck portion 134 connected to the cross-piece, and a distal gripping portion 136 extending from the narrow neck portion. The pair of resilient arms have an inner rounded surface 138 adapted to snap over the outer surface of the second dilator tube between the spaced apart rings of the second dilator tube. The second portion of the second locking clip includes a pair of resilient arms 142 each having a proximal narrow neck portion (not shown) connected to the cross-piece and a distal gripping portion 146 extending from the narrow neck portion, the pair of resilient arms having an inner rounded surface (not shown) adapted to fit over the outer surface of the third dilator tube to connect the second and third dilator tubes. Removing the second locking clip allows the third or outer dilator tube to slidably telescope over the second inner dilator tube to further dilate tissue at the distal end of the dilation introducer.
  • As is shown in FIG. 1, a tubular bone drill or tap 150 can be inserted through an intermediate or outer dilator tube, and the tubular bone drill or tap can be passed or threaded over a guide wire or K wire 151 to contact the surface of the vertebra or bone to be treated, as will be further described below. Once the outer dilator tube has been moved to the distal end of the dilation introducer into position against the vertebra or bone to be treated to fully dilate the soft tissue, the inner dilator tube, the tubular bone drill, and the intermediate dilator tube can be withdrawn and removed to leave the outer dilator tube in place to permit further surgical procedures.
  • Referring to FIGS. 8-12, the invention provides for a second presently preferred embodiment of a dilation introducer 160 shown in a locked assembled configuration in FIG. 8, and shown in an unlocked, collapsed configuration in FIG. 9. Referring to FIG. 10, the dilation introducer includes a first or inner dilator tube 162 having a distal end 164 with a tapered tip 166, and a proximal end 168 with a cylindrical head 170. The means for removably connecting the first and second dilator tubes together in a locked configuration includes a latching member 172, such as a hook, projecting from the cylindrical head toward the distal end, receiving a locking pin 216, although other latching members, such as a projection with aperture for receiving a locking pin may also be suitable, as will be apparent from the explanation below. The first dilator tube has an inner lumen 174 with a distal opening 176 and a proximal opening 178.
  • Referring to FIG. 11, the dilation introducer includes a shorter second or intermediate dilator tube 182 having a distal end 184 with a tapered tip 186, and a proximal end 188 having a cylindrical head 190. The means for removably connecting the second and third dilator tubes together in a locked configuration includes a latching member 192, such as a hook, projecting from the cylindrical head toward the distal end, receiving a locking pin 218, although other latching members, such as a projection with aperture for receiving a locking pin may also be suitable, as noted above. The second dilator tube has an inner lumen 194 with a distal opening 196, and a proximal opening 198. The cylindrical head includes a first radial aperture 200 for receiving the locking pin 216, and a second longitudinal aperture 201 for receiving the distally projecting latching member of the cylindrical head of the first or inner dilator tube.
  • Referring to FIG. 12, in a preferred aspect, the dilation introducer includes at least one additional dilator tube, such as a still shorter third or outer dilator tube 202 having a distal end 204 with a tapered tip 206, and a proximal end 208 to which a handle 210 is connected at its head end 212. The head end of the handle includes a radial aperture 214 for receiving the locking pin 218, and a longitudinal aperture 215 for receiving the distally projecting latching member of the cylindrical head of the second or intermediate dilator tube. The first locking pin 216 is substantially the same as the second locking pin 218. The third dilator tube has an inner lumen 219 with proximal and distal openings. A tubular bone drill or tap can be inserted through the first or inner dilator tube, and the tubular bone drill or tap can be threaded over a guide wire or K wire to contact the surface of the vertebra or bone to be treated, as described above.
  • With reference to FIGS. 13-18, the invention provides for a third presently preferred embodiment of a dilation introducer 220, shown in a locked assembled configuration in FIG. 13, and shown in an unlocked, collapsed configuration in FIG. 14. As is illustrated in FIG. 15, the dilation introducer includes a first or inner dilator tube 222 having a distal end 224 with a tapered, beveled tip 226, and a proximal end 228 with a cylindrical head 230. The means for removably connecting the first and second dilator tubes together in a locked configuration includes a pair of opposing bayonet pins 232 extending from the proximal end of the first dilator tube. The first dilator tube has an inner lumen 234 with a distal opening 236 and a proximal opening 238.
  • As is shown in FIG. 16, the dilation introducer includes a shorter second or intermediate dilator tube 242 having a distal end 244 with a tapered, beveled tip 246, and a proximal end 248 with a cylindrical head 250. In a preferred aspect, a means for removably connecting the second and third dilator tubes together in a locked configuration includes a pair of opposing bayonet pins 252. The second dilator tube has an inner lumen 254 with a distal opening 256 and a proximal opening 258, and as part of the means for removably connecting the second and third dilator tubes together, interior opposing bayonet slots 260 for receiving the pair of opposing bayonet pins of the first or inner dilator tube.
  • Referring to FIG. 17, in a preferred aspect, the dilation introducer includes at least one additional dilator tube, such as a still shorter third or outer dilator tube 262 having a distal end 264 with a tapered tip 266, and a proximal end 268 having a pair of opposing handles 270. The third dilator tube has an inner lumen 271, with proximal and distal openings. In another presently preferred aspect, a plastic sleeve 272 is slidably disposed over the shaft of the third or outer dilator tube, and the plastic sleeve preferably has a distal tapered, beveled end 274. A proximal sleeve ring 276 may also be slidably disposed over the shaft of the third or outer dilator tube between the plastic sleeve 272 and the opposing handles.
  • As is illustrated in FIGS. 13 and 14, in this embodiment the tapered tips of the dilator tubes and plastic sleeve are beveled or angled at a common angle with respect to the longitudinal axis of the dilation introducer, so that the beveled edges of the tapered tips of the dilator tubes and plastic sleeve can be aligned together generally parallel to the surface of the soft tissue to be dilated, so that the bore and dilation passage of the dilation introducer may be aligned at a predetermined desired angle with respect to the soft tissue to be dilated and the bone tissue to be treated.
  • As part of the means for removably connecting the second and third dilator tubes together, the third dilator tube includes interior opposing bayonet slots 278 for receiving the pair of opposing bayonet pins of the second or intermediate dilator tube. A tubular bone drill or tap can be inserted through the first or inner dilator tube, and the tubular bone drill or tap can be threaded over a guide wire or K wire to contact the surface of the vertebra or bone to be treated, as described above.
  • With reference to FIGS. 19-23, the invention provides for a fourth embodiment of a dilation introducer 280 shown in a locked assembled configuration in FIG. 19, and shown in an unlocked, collapsed configuration in FIG. 20. Referring to FIG. 21, the dilation introducer includes a first or inner dilator tube 282 having a distal end 284 with a tapered tip 286, and a proximal end 288 having a generally spherical handle or head 290. As part of a means for removably connecting first and second dilator tubes together in a locked configuration, the proximal end of the first dilator tube near the handle includes a bayonet pin 292. The first dilator tube has an inner lumen 294 with a distal opening 296, and a proximal opening 298.
  • Referring to FIG. 22, the dilation introducer includes a shorter second or intermediate dilator tube 302 having a distal end 304 with a tapered tip 306, and a proximal end 308 having a generally cylindrical head 310 and a pair of opposing handles 312. The second dilator tube has an inner lumen 314 with a distal opening 316 and a proximal opening 318. As part of the means for removably connecting first and second dilator tubes together in a locked configuration, the proximal end of the second dilator tube includes a bayonet slot 320 formed in the cylindrical head for receiving the bayonet pin of the first or inner dilator tube.
  • Referring to FIG. 23, in a preferred aspect, the dilation introducer includes at least one additional dilator tube, such as a still shorter third or outer dilator tube 322, currently preferably formed of plastic, having a distal end 324 with a tapered tip 326, and a proximal end 328 with a generally cylindrical head end or handle 330. The third dilator tube has an inner lumen 332, with proximal and distal openings. A tubular bone drill or tap can be inserted through the first or inner dilator tube, and the tubular bone drill or tap can be threaded over a guide wire or K wire to contact the surface of the vertebra or bone to be treated, as described above.
  • Facet Screw Surgical Technique:
  • Referring to FIGS. 24-26, a surgical method for spinal fusion utilizing the dilation introducer apparatus and a bone fixation device such as a bone fixation device available under the trade name BONE-LOK from Triage Medical, Inc. of Irvine, Calif., is described. Alternatively, other types of bone screws or fixation devices may also be suitable. The method of the invention involves dilating a patient's soft tissue down to bone tissue to be treated in orthopedic surgery, and necessarily entails an incision and fluoroscopy to locate an entry point on the bone tissue to be treated.
  • An entry point is located on the bone tissue to be treated, and the tip of a guide wire or K-wire 151 is placed at the entry point on the bone tissue to be treated shown in FIG. 25, and driven into the soft tissue of the patient to the target point of the inferior articular facet. A vertical midline incision to a desired depth, such as approximately 17 mm, is made in the skin and fascia of the patient, using the entry point as the middle of the incision. A first dilator tube of the dilation introducer is then passed over the guide wire until the tip of the dilation introducer reaches the target point of the bone. The guide wire is then driven into the facet joint and into the pedicle of the patient, with verification of the trajectory and depth by fluoroscopy. The second dilator tube of the dilation introducer is then released and passed over the first dilator tube to allow it to progress to the bone, allowing removal of the first dilator tube. This is repeated for the remaining, progressively wider telescoping dilator tubes, to progressively expand the patient's soft tissue down to the entry point on the bone tissue to be treated, and leaving an outer dilator tube port in place. A depth gauge is then used to verify that the appropriate depth has been reached. A pre-drill is advanced to the desired location, which is then also verified by fluoroscopy. A cortex drill is advanced until its positive stop engages, and the distal tip of a tap is driven into the bone until it reaches the appropriate depth, which is then also verified by fluoroscopy. The drill can be connected through an AO style quick connect, or a Jacobs chuck, as long as they are fully cannulated, to a ratcheting handle which is also preferably cannulated. A bone fixation device is then driven into the bone until it reaches the appropriate depth, which is then also verified by fluoroscopy. The bone fixation device is compressed to achieve appropriate stabilization, which is then also verified by fluoroscopy. Once compression of the bone fixation device has been achieved, the pull pin is removed, the guide wire is removed, and the remaining outer dilator tube port is removed, and the incision can be closed normally.
  • Referring to FIGS. 27-29, in one presently preferred embodiment, a guide wire or K wire assembly 340 for use with the telescoping dilation introducer of the invention includes an elongated, generally cylindrical first section 342 and an elongated, tubular second section 344 that is adapted to receive the first section. The first section includes a proximal enlarged head or stop portion 346, and a relatively narrow elongated body portion 348. The elongated body portion is preferably formed with a proximal section 350 having a relatively larger diameter to provide relatively greater strength, rigidity and torquability for manipulation of the guide wire, and a relatively narrower diameter main section 352 connected to the proximal section, and a pointed distal tip 354 at the distal end 358 of the main section. The elongated tubular second section has a relatively larger diameter than the main section and an internal bore slightly larger in diameter than the main section for receiving the main section, as is illustrated in FIG. 28. The tubular second section advantageously also includes a frustoconical distal tip 362 with a narrowed portion 364 at the distal end 366 of the tubular distal section, and presenting an enlarged flat shoulder 368 at the proximal end of the frustoconical distal tip, so that when the guide wire assembly is assembled as shown in FIG. 29, and the elongated main section is received in the internal bore of the elongated tubular section, and the proximal section of the elongated body portion of the elongated generally cylindrical section is seated against said proximal end of said elongated tubular section, the pointed distal tip extends out of said frustoconical distal tip of said elongated tubular section so that the assembly presents a pointed distal end, with a proximal shoulder against which a telescoping dilation introducer can be pushed for operation of the telescoping dilation introducer. The elongated generally cylindrical first section thus adds a sharp point to the relatively blunt distal end of the elongated tubular second section, allowing the guide wire assembly to be inserted through soft tissue for placement in a soft tissue target of interest, such as an organ. Since the soft tissue present no hard surface against which the telescoping dilation introducer can be pushed, after the sharp point of the guide wire is placed in the desired location in the soft tissue, the first section can be removed from the second section, leaving the blunt distal end in place at the desired location in the soft tissue, and the telescoping dilation introducer can be placed over the second section and pressed against the shoulder of the blunt distal end for operation of the telescoping dilation introducer.
  • As is shown in FIG. 30, in one presently preferred variation of the at least one additional or outer dilator tube, such as in the embodiment of FIGS. 8-12 for example, the outer dilator tube 400 includes a parallel guide insert 402, shown in FIG. 31. The outer dilator tube has a distal end 404 with a tapered tip 406, and a proximal portion 408 to which a handle 410 is connected at the extreme proximal or head end 412 of the outer dilator tube. The head end of the outer dilator tube includes a radial aperture 414 for receiving the locking pin 416, and a longitudinal aperture 418 for receiving a distally projecting latching member 420 of the cylindrical head 422 of the parallel guide insert. The outer dilator tube has an inner bore 424 with proximal and distal openings.
  • The parallel guide insert includes a main cylindrical shaft 425 connected at a proximal end 426 to the cylindrical head of the parallel guide insert. The parallel guide insert includes a plurality of longitudinal bores 428 extending the length of the parallel guide insert from the distal end 430, with distal openings visible in FIG. 31, to proximal openings (not shown) in the cylindrical head of the parallel guide insert. The insertion of the distally projecting latching member of the cylindrical head of the parallel guide insert in the longitudinal aperture of the head end of the handle of the outer dilator tube insures that the parallel guide insert remains in a fixed position in the outer dilator tube when the parallel guide insert is secured with the locking pin. A single guide wire or K wire or other device may be passed through one or more of the bores of the parallel guide insert, or multiple guide wires or K wires or other devices may be passed through a plurality of the bores simultaneously, as desired. However, the parallel guide insert may be provided without a latching member, in order to allow the parallel guide member to be rotated freely to allow alignment of the desired locations of the guide wires through the holes in the parallel guide insert.
  • Referring to FIG. 32, in another presently preferred variation of the at least one additional or outer dilator tube, such as in the embodiment of FIGS. 13-18 for example, the outer dilator tube 440 includes a parallel guide insert 442, shown in FIG. 33. The outer dilator tube has a distal end 444 with an angled tip 446, and a proximal end 448 to which a handle 450 is connected at the extreme proximal or head end 452 of the outer dilator tube. The head end of the outer dilator tube includes a radial aperture 454 for receiving the locking pin 456, and a longitudinal aperture 458 for receiving a distally projecting latching member 460 of the cylindrical head 462 of the parallel guide insert. The outer dilator tube has an inner bore 464 with proximal and distal openings.
  • The parallel guide insert includes a main cylindrical shaft 465 connected at a proximal end 466 to the cylindrical head of the parallel guide insert. The parallel guide insert includes a plurality of longitudinal bores 468 extending the length of the parallel guide insert from the angled distal end 470, with distal openings visible in FIG. 33, to proximal openings (not shown) in the cylindrical head of the parallel guide insert. The insertion of the distally projecting latching member of the cylindrical head of the parallel guide insert in the longitudinal aperture of the head end of the handle of the outer dilator tube insures that the parallel guide insert remains in a fixed position in the outer dilator tube when the parallel guide insert is secured with the locking pin. The angled tips of the outer dilator tube and the parallel guide insert are beveled or angled at a common angle with respect to the longitudinal axis of the dilation introducer, so that the angled tips of the outer dilator tube and the parallel guide insert can be aligned together generally parallel to the surface of the soft tissue to be dilated, with the bore and dilation passage of the dilation introducer aligned at a predetermined desired angle with respect to the soft tissue to be dilated and the bone tissue to be treated. A single guide wire or K wire or other device may be passed through one or more of the bores of the parallel guide insert, or multiple guide wires or K wires or other devices may be passed through a plurality of the bores simultaneously, as desired.
  • Referring to FIG. 34, in a variation of the outer dilator tube of the embodiment of FIGS. 32-33, the distal tip 480 of an outer dilator tube 482 may be angled or beveled, and may include a plurality of spikes 484 to provide for increased traction of the tip of the outer dilator tube on bone tissue. The spikes may be formed of radiopaque material, such as gold, platinum, tantalum or the like, for use with fluoroscopy. As is illustrated in FIG. 35, a parallel guide 486 disposed in the outer dilator tube has a distal tip 488 that may optionally also be provided with a plurality of embedded spikes 490 for increased traction on bone tissue. The spikes of the outer dilator tube and parallel guide may formed with a rounded shape so as to deflect soft tissue during dilation, and to provide increased traction with bone upon completion of the insertion of the dilator.
  • Referring to FIGS. 36-43, the invention provides for a fifth presently preferred embodiment of a dilation introducer 500, which is similar to the embodiment illustrated in FIGS. 8-12, and which is shown in an unlocked configuration in FIG. 36. Referring to FIGS. 36-37, the dilation introducer includes a first or inner dilator tube 502 having distal end (not shown) and a proximal end 504 with a cylindrical head 506. The means for removably connecting the first and second dilator tubes together in a locked configuration includes a first latching member 508, having a shaft 510 and a latching end 512, such as a hook, projecting from the cylindrical head toward the distal end, and connected to a locking button 514, which extends transversely out through a side aperture 516 in the cylindrical head. The locking button includes a shaft 518 and an enlarged head 520 connected to the shaft, and the locking button is biased outwardly from the cylindrical head by a spring 522. The latching member is received in an upper aperture 524 of the adjacent cylindrical head of a second or intermediate dilator tube 526, having a side opening latching chamber 528 for retaining the latching end of the latching member when the locking button is biased outwardly by its spring, to lock the cylindrical heads of the first and second dilator tubes together. The cylindrical heads of the first and second dilator tubes can be unlocked and separated by manually depressing the locking button to move the latching member inwardly and the latching end of the latching member inwardly out of the side opening latching chamber. In all other aspects, the first dilator tube is essentially the same as the first dilator tube of the embodiment of FIGS. 8-12.
  • The second or intermediate dilator tube 526 of the dilation introducer has a distal end (not shown) and a proximal end 530 with a cylindrical head 532. The means for removably connecting the second and third dilator tubes together in a locked configuration includes a second latching member 534, having a shaft 536 and a latching end 538, such as a hook, projecting from the cylindrical head toward the distal end, and connected to a second locking button 540, which extends transversely out through a side aperture 542 in the cylindrical head. The locking button includes a shaft 544 and an enlarged head 546 connected to the shaft, and the locking button is biased outwardly from the cylindrical head by a spring 548. The latching member is received in an upper aperture 550 of the adjacent cylindrical head of a third or second intermediate dilator tube 552, having a side opening latching chamber 554 for retaining the latching end of the latching member when the locking button is biased outwardly by its spring, to lock the cylindrical heads of the second and third dilator tubes together. The cylindrical heads of the second and third dilator tubes can be unlocked and separated by manually depressing the second locking button to move the latching member inwardly and the latching end of the latching member inwardly out of the side opening latching chamber. In all other aspects, the second dilator tube is essentially the same as the second dilator tube of the embodiment of FIGS. 8-12.
  • The third, or second intermediate, dilator tube 552 of the dilation introducer has a distal end (not shown) and a proximal end 556 with a cylindrical head 558. The means for removably connecting the third dilator tube and the outer dilator tube 560 together in a locked configuration includes a third latching member 562, having a shaft 564 and a latching end 566, such as a hook, projecting from the cylindrical head toward the distal end, and connected to a third locking button 568, which extends transversely out through a side aperture 570 in the cylindrical head. The third locking button includes a shaft 572 and an enlarged head 574 connected to the shaft, and the third locking button is biased outwardly from the cylindrical head by a spring 576. The latching member is received in an upper aperture 578 of the adjacent cylindrical head 580 of the outer dilator tube, having a side opening latching chamber 582 for retaining the latching end of the latching member when the locking button is biased outwardly by its spring, to lock the cylindrical heads of the third and outer dilator tubes together. The cylindrical heads of the third and outer dilator tubes can be unlocked and separated by manually depressing the third locking button to move the latching member inwardly and the latching end of the latching member inwardly out of the side opening latching chamber. In all other aspects, the third dilator tube is essentially the same as the second dilator tube of the embodiment of FIGS. 8-12.
  • Referring to FIG. 36, the outer dilator tube includes a distal end (not shown) and a proximal end 584 to which a handle 586 is connected at its cylindrical head end. The head end of the handle preferably includes a plurality of the upper apertures 578 connected to corresponding side opening latching apertures 582 for receiving the latching member of the adjacent dilator tube cylindrical head, as is illustrated in FIG. 40. Although three locking locations 588 of the upper apertures and corresponding side opening latching apertures in the cylindrical head of the outer dilator tube are shown, more or fewer locking locations may be provided, and the locking locations may be provided at various positions, to aid in user flexibility as to which hand to use during the dilation procedure, as well as varying the position of the inner dilator tubes and optionally a parallel guide member during use or guide pin placement. In all other aspects, the outer dilator tube is essentially the same as the outer dilator tube of the embodiment of FIGS. 8-12.
  • Referring to FIGS. 38 and 39, in a variation of the embodiment shown in FIGS. 36 and 37, the side opening latching chambers of the cylindrical heads of the dilator tubes may be closed so as to form covered latching chambers 590 a, b, c for the latching members. In all other aspects, the variation shown in FIGS. 38 and 39 is essentially the same as in FIGS. 36 and 37.
  • Referring to FIGS. 41-43, in another variation, an outer dilation tube 600 may be provided with a light emitter 602, such as one or more light emitting diodes (LEDs) or the end of a fiber optic, connected to or embedded in the tubular shaft 604 of the outer dilation tube, and preferably near the distal end 606 of the tubular shaft. As is illustrated in FIGS. 41 and 42, the light emitter may be an LED embedded in the wall 608 of the tubular shaft, with the LED directed to illuminate the interior, exterior, or distal edge of the tubular shaft of the outer dilation tube. As is shown in FIG. 42, one or more elongated energy conducting members 610, such as electrically conductive wires or fiber optics, for example, may be embedded in the tubular shaft, for conducting electricity or light to the light emitter. Referring to FIG. 41, the handle 612 of the outer dilator tube preferably contains one or more batteries 614 connected to a switch 616 which is in turn connected to power the light emitter. The handle may be provided with a battery or batteries, which may be disposable, a switch, resistor and other associated electronics, so that the handle is disposable, or alternatively the handle may be provided with a connector for connection to an external power source. In a presently preferred aspect, the switch is a thumb switch conveniently located on the handle adjacent to the cylindrical head 618 of the outer dilation tube. The handle, cylindrical head, and tubular shaft of the outer dilation tube preferably includes one or more channels 620 for the electrical wires connecting the one or more batteries to the switch and to the light emitter. When the light emitter includes one or more fiber optics, a light source 622 such as one or more LEDs providing light to be conducted through the one or more fiber optics may be placed adjacent to the switch in the handle, with the one or more fiber optics extending through the wall of the tubular shaft of the outer dilator tube.
  • Referring to FIG. 43, in another variation of the dilation introducer of FIG. 41, the one or more elongated energy conducting members, such as one or more wires or one or more fiber optics, may be disposed on the outer surface of the tubular shaft of the outer dilation tube. In a presently preferred aspect, the tubular shaft of the outer dilation tube may be formed with a groove 620 running longitudinally on the exterior surface of the tubular shaft, parallel to the longitudinal axis of the outer dilation tube, to accommodate one or more wires or one or more fiber optics. Alternatively, the one or more elongated energy conducting members may be located on the inside of the dilator tube, or may extend through the wall of the dilator tube.
  • Referring to FIGS. 44-46, the present invention also provides for a telescoping expander sleeve 630 that is adapted to be slidably disposed over the shaft of an outer dilator tube of any of the foregoing embodiments for expanding the patient's soft tissue down to the entry point on the bone tissue to be treated, while leaving the outer dilator tube in place, or allowing for replacement of the outer dilator tube with other equipment for treatment of the bone tissue. The tubular proximal portion may optionally be provided with a handle. The expander sleeve may be pre-assembled in combination with one or more of the dilation introducers, adapted to be ready for use. The telescoping expander sleeve has a first or inner generally tubular section 632, having a tubular proximal portion 634 with an enlarged proximal head 636, and a distal portion 638 with at least two substantially identical opposing active spreader arms 640 (one of which is not visible in FIGS. 44-46) connected at one end to the tubular proximal portion and moveable radially at their distal tips 642. The distal tips of the active spreader arms preferably have beveled edges 644 to deflect soft tissue during insertion of the telescoping expander sleeve.
  • A second or outer generally tubular section 646 is slidably disposed over the first or inner generally tubular section, and includes a tubular proximal portion 648 and a distal portion 650 with at least two substantial identical opposing passive spreader flaps 652 interposed between the active spreader arms, hingedly connected to the tubular proximal portion at proximal ends 654, and moveable radially at their distal tips 656. The distal tips of the passive spreader flaps preferably also have beveled edges to deflect soft tissue during insertion of the telescoping expander sleeve. The distal tips of the passive spreader flaps when placed together in an unexpanded configuration have a generally circular configuration, so that the distal tips of two passive spreader flaps, for example, have a semi-circular configuration. The passive spreader flaps taper progressively toward their narrowed proximal ends connected to the tubular proximal portion of the outer tubular section. In a presently preferred aspect, the passive spreader flaps are connected to the tubular proximal portion of the outer generally tubular section by rings 656 passing through apertures 658 and 660 in the adjacent ends of the tubular proximal portion and the passive spreader flaps, respectively.
  • The active spreader arms are slidably interposed between and engage the passive spreader flaps, so that as the telescoping expander sleeve telescopes from an extended, unexpanded configuration to a collapsed, expanded configuration, as shown in FIG. 44, the active spreader arms slide from the narrow proximal ends of the passive spreader flaps to the wider distal ends of the passive spreader flaps to spread the distal ends of the passive spreader flaps apart, which also forces the distal ends of the active spreader arms apart, as shown in FIG. 46. In a presently preferred aspect, the distal ends of the active spreader arms are slidably connected to slots 662 extending along the inner edges 664 of the passive spreader flaps by loops or rings 666, such as loops of nylon filament or metal rings, for example, which pass through apertures 668 in the distal ends of the active spreader arms. Telescoping of expander sleeve from a collapsed, expanded configuration to an extended, unexpanded configuration thus slides the distal ends of the active spreader arms of the inner tubular section from the wide distal ends of the passive spreader flaps along the inner edges of the passive spreader flaps to the narrowed proximal ends of the passive spreader flaps, to bring the passive spreader flaps together. The purpose of the active spreader arms and passive spreader flaps is to facilitate the creating of a larger working area adjacent to bone or bone tissues being treated. The spreader arms and flaps may optionally be covered by an expandable material, such as latex, for example, with a central through hole permitting operation of the device, to cover the spreader arms and flaps to prevent tissues from being pressed into cavities of the telescoping expander sleeve.
  • In the foregoing embodiments, the components of the dilation introducer may be formed from plastic, stainless steel, or similar materials or combinations thereof, that can be readily sterilized and packaged ready for use, after which the dilation introducer may be disposed of or resterilized for subsequent use, as desired. The dilator tubes may be radioluscent, with radiopaque markers located on the tips of one or more of the dilator tubes. The tip of the first dilator may also be scored, grooved, or otherwise be provided with a rough surface, to prevent migration. The dilation introducer may also have curved or otherwise non-linear dilator tubes, and the dilation introducer may also have a non-cylindrical shape, such as an oval shape, for example, to allow the dilation introducer to be inserted around objects or a patient's organs.
  • It should also be appreciated that one or more devices can be inserted through the same dilation introducer, and that the dilation introducer can be repositioned within the same incision for fixation of multiple devices. In addition, fiber optic devices may be inserted through or integrated with the dilation introducer for visual inspection of the target area. While particular locking features have been described for the different embodiments of the dilation introducer, any combination of locking features or alternate locking features may be utilized. The outer dilator tube may not be locked, and a handle on the outer dilator tube may simply be used as a stop. It should also be appreciated that while the invention has been described as being used in the context of orthopedic surgery, and more particularly for implantation of bone fixation devices, the dilation introducer of the invention can also be useful in dilation of soft tissue for percutaneous, minimally invasive surgical procedures such as nephrostomy, neurosurgery, heart valve repair or replacement, gastrointestinal surgery such as for gall bladder or gall stone surgery, hernia removal, transjugular intrahepatic portal-systemic shunt (TIPS) procedures for treatment of the liver, and the like.
  • It will be apparent from the foregoing that, while particular forms of the invention have been illustrated and described, various modifications can be made without departing from the spirit and scope of the invention. Accordingly, it is not intended that the invention be limited, except as by the appended claims.

Claims (23)

1. In a dilation introducer for surgery on an internal body structure, the dilation introducer having a locked assembled configuration for initial placement of the dilation introducer against a patient's bone tissue to be treated, and an unlocked, collapsed configuration dilating the patient's soft tissue down to the tissue to be treated to a desired degree of dilation to permit minimally invasive surgical procedures on the patient's tissue to be treated, the improvement in the dilation introducer comprising:
at least one dilator tube having a distal end and a proximal end, the distal end of the at least one dilator tube including a plurality of spikes.
2. The dilation introducer of claim 1, wherein said spikes are formed of radiopaque material.
3. The dilation introducer of claim 1, wherein said spikes are formed are formed with a rounded shape so as to deflect soft tissue.
4. The dilation introducer of claim 1, further comprising a parallel guide insert adapted to be received in said at least one additional dilator tube, said parallel guide insert including a main cylindrical shaft having a proximal end connected to a cylindrical head, and a plurality of longitudinal bores extending the length of the parallel guide insert through the main cylindrical shaft and cylindrical head, and wherein parallel guide insert has a distal tip with a plurality of spikes.
5. The dilation introducer of claim 4, wherein said spikes are formed of radiopaque material.
6. The dilation introducer of claim 4, wherein said spikes are formed are formed with a rounded shape so as to deflect soft tissue.
7. A dilation introducer for surgery on an internal structure to be treated, the dilation introducer having a locked assembled configuration for initial placement of the dilation introducer against a patient's tissue to be treated, and an unlocked, collapsed configuration dilating the patient's soft tissue down to the tissue to be treated to a desired degree of dilation to permit minimally invasive surgical procedures on the patient's tissue to be treated, comprising:
a first dilator tube having a distal end with a tapered tip and a proximal end with a cylindrical head;
a second dilator tube, the first dilator tube being removably received in the second dilator tube for slidable telescoping movement within the second dilator tube, the second dilator tube having a distal end with a tapered tip and a proximal end with a cylindrical head, and an inner lumen with a distal opening and a proximal opening; and
means for removably connecting the first and second dilator tubes together in a locked configuration including a first latching member disposed in the cylindrical head of the first dilator tube, the first latching member having locking button connected transversely to a shaft with a latching end projecting from the cylindrical head of the first dilator tube toward the distal end of the first dilator tube, the locking button extending transversely from the shaft through a side aperture in the cylindrical head of the first dilator tube, the locking button being biased outwardly from the cylindrical head, the first latching member being received in an upper aperture of the cylindrical head of the second dilator tube, the upper aperture of the cylindrical head of the second dilator tube having a latching chamber for retaining the latching end of the latching member when the locking button is biased outwardly, to lock the cylindrical heads of the first and second dilator tubes together, the locking button being moveable inwardly to move the latching member inwardly and the latching end of the latching member inwardly out of the latching chamber.
8. The dilation introducer of claim 7, further comprising at least one additional dilator tube, the second dilator tube being removably received in the at least one additional dilator tube for slidable telescoping movement within the at least one additional dilator tube, the at least one additional dilator tube having a distal end and a proximal end with a cylindrical head, an inner lumen with a distal opening and a proximal opening, the distal end having a tapered tip, the second dilator tube and the at least one additional dilator tube having an unlocked configuration in which the at least one additional dilator tube is permitted to slidably telescope over the second dilator tube to dilate the patient's soft tissue at the distal end of the dilation introducer; and
means for removably connecting the second dilator tube and the at least one additional dilator tube together in a locked configuration including a second latching member disposed in the cylindrical head of the second dilator tube, the second latching member having locking button connected transversely to a shaft with a latching end projecting from the cylindrical head of the second dilator tube toward the distal end of the second dilator tube, the locking button extending transversely from the shaft through a side aperture in the cylindrical head of the second dilator tube, the locking button being biased outwardly from the cylindrical head, the second latching member being received in an upper aperture of the cylindrical head of the at least one additional dilator tube, the upper aperture of the cylindrical head of the at least one additional dilator tube having a latching chamber for retaining the latching end of the second latching member when the locking button is biased outwardly, to lock the cylindrical heads of the second and at least one additional dilator tubes together, the locking button being moveable inwardly to move the second latching member inwardly and the latching end of the second latching member inwardly out of the latching chamber.
9. The dilation introducer of claim 8, wherein said at least one additional dilator tube comprises a handle connected to the proximal end of said at least one additional dilator tube, and the cylindrical head of said at least one additional dilator tube including a plurality of said upper apertures each including one said latching chamber for receiving the second latching member.
10. In a dilation introducer for orthopedic surgery, the dilation introducer having a locked assembled configuration for initial placement of the dilation introducer against a patient's tissue to be treated, and an unlocked, collapsed configuration dilating the patient's soft tissue down to the tissue to be treated to a desired degree of dilation to permit minimally invasive surgical procedures on the patient's tissue to be treated, the improvement in the dilation introducer comprising:
at least one dilator tube having a tubular shaft, a distal end and a proximal end, an inner lumen with a distal opening and a proximal opening; and
a light emitter disposed in said at least one additional dilator tube.
11. The dilation introducer of claim 10, wherein said light emitter comprises a light emitting diode.
12. The dilation introducer of claim 11, wherein said light emitting diode is embedded in said tubular shaft of said at least one dilator tube.
13. The dilation introducer of claim 10, wherein said light emitter comprises a fiber optic.
14. The dilation introducer of claim 13, wherein said fiber optic is embedded in said tubular shaft of said at least one dilator tube.
15. The dilation introducer of claim 10, wherein said at least one dilator tube comprises a handle and a switch for controlling said light emitter, and at least one battery is disposed in said handle, said at least one battery being connected to said switch to power said light emitter.
16. The dilation introducer of claim 13, wherein said light emitter further comprises a light source providing light conducted to said at least one fiber optic.
17. The dilation introducer of claim 10, wherein said light emitter comprises at least one elongated energy conducting member disposed on an outer surface of the tubular shaft of said at least one dilator tube.
18. The dilation introducer of claim 17, wherein said at least one elongated energy conducting member is disposed in a groove on the exterior surface of the tubular shaft.
19. A telescoping expander sleeve adapted to be slidably disposed over a shaft of a dilator tube for dilating a patient's soft tissue down to tissue to be treated to a desired degree of dilation to permit minimally invasive surgical procedures on the patient's tissue to be treated, the telescoping expander sleeve being moveable between an extended, unexpanded configuration and a collapsed, expanded configuration, the telescoping expander sleeve comprising:
a first generally tubular section having a tubular proximal portion and a distal portion, the tubular proximal portion having an enlarged proximal head, and the distal portion including at least two active spreader arms each having a proximal end and a distal tip, said at least two active spreader arms being connected at the proximal end, respectively, to the tubular proximal portion, said distal tips of said at least two active spreader arms being moveable radially between an unexpanded configuration and an expanded configuration;
a second generally tubular section slidably disposed over the first generally tubular section, said second generally tubular section including a tubular proximal portion and a distal portion including at least two passive spreader flaps each having a narrow proximal end and a wide distal tip, said proximal ends of said at least two passive spreader flaps being hingedly connected to said tubular proximal portion, said distal tips of said at least two passive spreader flaps being moveable radially between an unexpanded configuration and an expanded configuration, said at least two active spreader arms slidably engaging said at least two passive spreader flaps, so that as the telescoping expander sleeve telescopes from the extended, unexpanded configuration to a collapsed, expanded configuration, said at least two active spreader arms slide from the narrow proximal ends of said at least two passive spreader flaps to the wider distal ends of the passive spreader flaps to spread the distal ends of said at least two passive spreader flaps apart and to spread the distal ends of said at least two active spreader arms apart.
20. The telescoping expander sleeve of claim 19, wherein the distal tips of said at least two active spreader arms have beveled edges to deflect soft tissue during insertion of the telescoping expander sleeve.
21. The telescoping expander sleeve of claim 19, wherein the distal tips of said at least two passive spreader flaps have beveled edges to deflect soft tissue during insertion of the telescoping expander sleeve.
22. A guide wire assembly for use with a telescoping dilation introducer in treatment of soft tissue, to provide a surface against which the telescoping dilation introducer can be pushed during operation of the telescoping dilation introducer, comprising:
an elongated tubular section having a proximal end, a distal end, an internal bore, and a frustoconical distal tip with a narrowed portion at the distal end and an enlarged flat shoulder at a proximal portion of the frustoconical distal tip; and
an elongated generally cylindrical section removably received in said internal bore of said elongated tubular section, the elongated generally cylindrical section having a proximal enlarged head and an elongated body portion, said elongated body portion having a proximal end and a distal end, said distal end having a pointed distal tip, such that when said elongated generally cylindrical section is received in said elongated tubular section, said pointed distal tip extends out of the distal end of said frustoconical distal tip to present a sharp point that can be positioned in soft tissue, and such that when said elongated generally cylindrical section is thereafter removed, said enlarged flat shoulder of said frustoconical distal tip provides a surface against which a telescoping dilation introducer can be pushed for operation of the telescoping dilation introducer in treatment of soft tissue.
23. The guide wire assembly of claim 22, wherein said elongated body portion of said elongated generally cylindrical section includes a proximal section adjacent to said proximal enlarged head and an elongated main section connected to the proximal section, said proximal section having a diameter larger than an outer diameter of said elongated tubular section, and said elongated main section having a diameter narrower than the diameter of said internal bore of said elongated tubular section so as to be receivable in said internal bore of said elongated tubular section, such that when said elongated main section is received in said internal bore of said elongated tubular section and said proximal section of the elongated body portion of the elongated generally cylindrical section is seated against said proximal end of said elongated tubular section, said pointed distal tip extends out of said frustoconical distal tip of said elongated tubular section so that said guide wire assembly presents a pointed distal end.
US11/038,784 2002-11-14 2005-01-19 Dilation introducer for orthopedic surgery Abandoned US20050256525A1 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
US11/659,025 US9387313B2 (en) 2004-08-03 2005-08-02 Telescopic percutaneous tissue dilation systems and related methods
EP05777628.8A EP1773438B1 (en) 2004-08-03 2005-08-02 Telescopic percutaneous tissue dilation systems
EP16207090.8A EP3205371B1 (en) 2004-08-03 2005-08-02 Telescopic percutaneous tissue dilation systems and related methods of producing
PCT/US2005/027431 WO2006017507A2 (en) 2004-08-03 2005-08-02 Telescopic percutaneous tissue dilation systems and related methods
JP2007524917A JP5164571B2 (en) 2004-08-03 2005-08-02 Percutaneous tissue expansion system and related methods
US15/186,963 US10293147B2 (en) 2004-08-03 2016-06-20 Telescopic percutaneous tissue dilation systems and related methods

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US42613702P 2002-11-14 2002-11-14
US50205003P 2003-09-10 2003-09-10
US10/714,333 US8090542B2 (en) 2002-11-14 2003-11-14 Functional and hyperfunctional siRNA
US11/083,784 US7820809B2 (en) 2002-11-14 2005-03-18 Functional and hyperfunctional siRNA directed against Bcl-2

Related Parent Applications (2)

Application Number Title Priority Date Filing Date
US10/714,333 Continuation US8090542B2 (en) 2002-11-14 2003-11-14 Functional and hyperfunctional siRNA
US10/911,215 Continuation-In-Part US20060030872A1 (en) 2004-08-03 2004-08-03 Dilation introducer for orthopedic surgery

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US10/911,215 Continuation-In-Part US20060030872A1 (en) 2004-08-03 2004-08-03 Dilation introducer for orthopedic surgery
US11/659,025 Continuation-In-Part US9387313B2 (en) 2004-08-03 2005-08-02 Telescopic percutaneous tissue dilation systems and related methods

Publications (1)

Publication Number Publication Date
US20050256525A1 true US20050256525A1 (en) 2005-11-17

Family

ID=32329096

Family Applications (52)

Application Number Title Priority Date Filing Date
US10/714,333 Expired - Fee Related US8090542B2 (en) 2002-11-14 2003-11-14 Functional and hyperfunctional siRNA
US10/940,892 Abandoned US20120052487A9 (en) 2002-11-14 2004-09-14 Methods and compositions for selecting sirna of improved functionality
US11/038,784 Abandoned US20050256525A1 (en) 2002-11-14 2005-01-19 Dilation introducer for orthopedic surgery
US11/083,784 Expired - Fee Related US7820809B2 (en) 2002-11-14 2005-03-18 Functional and hyperfunctional siRNA directed against Bcl-2
US11/093,832 Abandoned US20070039072A1 (en) 2002-11-14 2005-03-29 Functional and hyperfunctional siRNA
US11/095,383 Active 2027-05-09 US7834170B2 (en) 2002-11-14 2005-03-30 Functional and hyperfunctional siRNA
US11/101,244 Active 2026-02-28 US7691997B2 (en) 2002-11-14 2005-04-07 Functional and hyperfunctional siRNA
US11/633,404 Abandoned US20070093653A1 (en) 2002-11-14 2006-12-04 siRNA targeting MCL1
US11/633,383 Expired - Lifetime US7645869B2 (en) 2002-11-14 2006-12-04 siRNA targeting spleen tyrosine kinase
US11/633,342 Expired - Fee Related US7608707B2 (en) 2002-11-14 2006-12-04 siRNA targeting survivin
US11/633,306 Expired - Lifetime US7507811B2 (en) 2002-11-14 2006-12-04 siRNA targeting KRAS
US11/635,618 Expired - Fee Related US7579457B2 (en) 2002-11-14 2006-12-07 siRNA targeting carbonic anhydrase II
US11/635,478 Abandoned US20070088155A1 (en) 2002-11-14 2006-12-07 siRNA targeting tumor necrosis factor superfamily member 1A
US11/635,330 Expired - Lifetime US7696344B2 (en) 2002-11-14 2006-12-07 siRNA targeting complement factor B
US11/635,329 Expired - Fee Related US7674896B2 (en) 2002-11-14 2006-12-07 siRNA targeting BCL2L1
US11/880,628 Expired - Fee Related US7595389B2 (en) 2002-11-14 2007-07-23 siRNA targeting casitas B cell lymphoma-B (CBL-B)
US11/880,775 Expired - Lifetime US7655788B2 (en) 2002-11-14 2007-07-24 siRNA targeting DNA-damage-inducible transcript 4 (DDIT4)
US11/880,777 Abandoned US20080188648A1 (en) 2002-11-14 2007-07-24 siRNA targeting human hairless protein (HR)
US11/880,855 Abandoned US20080300395A1 (en) 2002-11-14 2007-07-24 siRNA targeting vascular endothelial growth factor receptor 1 (VEGFR1)
US11/880,755 Abandoned US20080293595A1 (en) 2002-11-14 2007-07-24 siRNA targeting protein tyrosine phosphatase-1B (PTP1B)
US11/881,386 Abandoned US20080221317A1 (en) 2002-11-14 2007-07-25 siRNA targeting cystic fibrosis transmembrane conductance regulator (CFTR)
US11/881,385 Abandoned US20080306015A1 (en) 2002-11-14 2007-07-25 siRNA targeting proprotein convertase subtilisin/kexin type 9 (PCSK9)
US11/903,001 Expired - Lifetime US7514550B2 (en) 2002-11-14 2007-09-20 siRNA targeting myeloid cell leukemia sequence 1
US11/974,610 Abandoned US20080091001A1 (en) 2002-11-14 2007-10-15 Functional and hyperfunctional siRNA directed against Bcl-2
US11/974,878 Abandoned US20080114162A1 (en) 2002-11-14 2007-10-16 Functional and hyperfunctional siRNA directed against Bcl-2
US11/974,865 Abandoned US20080091002A1 (en) 2002-11-14 2007-10-16 Functional and hyperfunctional siRNA directed against Bcl-2
US11/974,880 Abandoned US20080091003A1 (en) 2002-11-14 2007-10-16 Functional and hyperfunctional siRNA directed against Bcl-2
US11/974,885 Expired - Lifetime US7511132B2 (en) 2002-11-14 2007-10-16 Functional and hyperfunctional siRNA directed against Bcl-2
US11/975,152 Expired - Fee Related US7795420B2 (en) 2002-11-14 2007-10-17 Functional and hyperfunctional siRNA directed against Bcl-2
US11/975,331 Abandoned US20080091004A1 (en) 2002-11-14 2007-10-18 Functional and hyperfunctional siRNA directed against Bcl-2
US11/975,661 Abandoned US20080108803A1 (en) 2002-11-14 2007-10-19 Functional and hyperfunctional siRNA directed against Bcl-2
US12/157,137 Expired - Lifetime US7642349B2 (en) 2002-11-14 2008-06-06 siRNA targeting TATA box binding protein (TBP)-associated factor (TAF1)
US12/287,757 Expired - Fee Related US7576196B2 (en) 2002-11-14 2008-10-14 siRNA targeting transducin (beta)-like 3 (TBL3)
US12/330,981 Expired - Fee Related US7576197B2 (en) 2002-11-14 2008-12-09 SiRNA targeting KRAS
US12/322,980 Abandoned US20090163701A1 (en) 2002-11-14 2009-02-10 siRNA targeting tumor necrosis factor receptor superfamily member 1A
US12/378,164 Expired - Fee Related US7592444B2 (en) 2002-11-14 2009-02-11 siRNA targeting myeloid cell leukemia sequence 1
US12/384,768 Expired - Lifetime US8030474B2 (en) 2002-11-14 2009-04-08 siRNA targeting cyclin-dependent kinase 4 (CDK4)
US12/459,489 Abandoned US20090291497A1 (en) 2002-11-14 2009-07-01 siRNA targeting transducin (beta)-like 3 (TBL3)
US12/459,670 Expired - Fee Related US7745611B2 (en) 2002-11-14 2009-07-06 siRNA targeting KRAS
US12/463,000 Abandoned US20100004142A1 (en) 2002-11-14 2009-08-12 siRNA targeting myeloid cell Leukemia sequence 1
US12/584,705 Expired - Fee Related US7807819B2 (en) 2002-11-14 2009-09-10 siRNA targeting survivin
US12/590,707 Expired - Lifetime US7803933B2 (en) 2002-11-14 2009-11-12 siRNA targeting TATA box binding protein (TBP)-associated factor (TAF1)
US12/592,335 Expired - Lifetime US7893247B2 (en) 2002-11-14 2009-11-23 siRNA targeting spleen tyrosine kinase
US12/657,263 Abandoned US20100152064A1 (en) 2002-11-14 2010-01-15 siRNA targeting BCL2L1
US12/799,844 Expired - Fee Related US8008474B2 (en) 2002-11-14 2010-05-03 siRNA targeting KRAS
US12/802,647 Expired - Lifetime US8000902B2 (en) 2002-11-14 2010-06-11 Methods and compositions for selecting siRNA of improved functionality
US12/806,320 Expired - Lifetime US7985854B2 (en) 2002-11-14 2010-08-10 siRNA targeting TATA box binding protein (TBP)-associated factor (TAF1)
US12/806,513 Abandoned US20100331214A1 (en) 2002-11-14 2010-08-13 siRNA Targeting Survivin
US12/928,190 Expired - Fee Related US8093370B2 (en) 2002-11-14 2010-12-06 siRNA targeting spleen tyrosine kinase
US13/199,001 Abandoned US20110319474A1 (en) 2002-11-14 2011-08-17 siRNA targeting cyclin-dependent kinase 4 (CDK4)
US13/373,956 Abandoned US20120135892A1 (en) 2002-11-14 2011-12-06 siRNA targeting spleen tyrosine kinase
US16/292,513 Abandoned US20190345573A1 (en) 2002-11-14 2019-03-05 Methods and Compositions for Selecting siRNA of Improved Functionality

Family Applications Before (2)

Application Number Title Priority Date Filing Date
US10/714,333 Expired - Fee Related US8090542B2 (en) 2002-11-14 2003-11-14 Functional and hyperfunctional siRNA
US10/940,892 Abandoned US20120052487A9 (en) 2002-11-14 2004-09-14 Methods and compositions for selecting sirna of improved functionality

Family Applications After (49)

Application Number Title Priority Date Filing Date
US11/083,784 Expired - Fee Related US7820809B2 (en) 2002-11-14 2005-03-18 Functional and hyperfunctional siRNA directed against Bcl-2
US11/093,832 Abandoned US20070039072A1 (en) 2002-11-14 2005-03-29 Functional and hyperfunctional siRNA
US11/095,383 Active 2027-05-09 US7834170B2 (en) 2002-11-14 2005-03-30 Functional and hyperfunctional siRNA
US11/101,244 Active 2026-02-28 US7691997B2 (en) 2002-11-14 2005-04-07 Functional and hyperfunctional siRNA
US11/633,404 Abandoned US20070093653A1 (en) 2002-11-14 2006-12-04 siRNA targeting MCL1
US11/633,383 Expired - Lifetime US7645869B2 (en) 2002-11-14 2006-12-04 siRNA targeting spleen tyrosine kinase
US11/633,342 Expired - Fee Related US7608707B2 (en) 2002-11-14 2006-12-04 siRNA targeting survivin
US11/633,306 Expired - Lifetime US7507811B2 (en) 2002-11-14 2006-12-04 siRNA targeting KRAS
US11/635,618 Expired - Fee Related US7579457B2 (en) 2002-11-14 2006-12-07 siRNA targeting carbonic anhydrase II
US11/635,478 Abandoned US20070088155A1 (en) 2002-11-14 2006-12-07 siRNA targeting tumor necrosis factor superfamily member 1A
US11/635,330 Expired - Lifetime US7696344B2 (en) 2002-11-14 2006-12-07 siRNA targeting complement factor B
US11/635,329 Expired - Fee Related US7674896B2 (en) 2002-11-14 2006-12-07 siRNA targeting BCL2L1
US11/880,628 Expired - Fee Related US7595389B2 (en) 2002-11-14 2007-07-23 siRNA targeting casitas B cell lymphoma-B (CBL-B)
US11/880,775 Expired - Lifetime US7655788B2 (en) 2002-11-14 2007-07-24 siRNA targeting DNA-damage-inducible transcript 4 (DDIT4)
US11/880,777 Abandoned US20080188648A1 (en) 2002-11-14 2007-07-24 siRNA targeting human hairless protein (HR)
US11/880,855 Abandoned US20080300395A1 (en) 2002-11-14 2007-07-24 siRNA targeting vascular endothelial growth factor receptor 1 (VEGFR1)
US11/880,755 Abandoned US20080293595A1 (en) 2002-11-14 2007-07-24 siRNA targeting protein tyrosine phosphatase-1B (PTP1B)
US11/881,386 Abandoned US20080221317A1 (en) 2002-11-14 2007-07-25 siRNA targeting cystic fibrosis transmembrane conductance regulator (CFTR)
US11/881,385 Abandoned US20080306015A1 (en) 2002-11-14 2007-07-25 siRNA targeting proprotein convertase subtilisin/kexin type 9 (PCSK9)
US11/903,001 Expired - Lifetime US7514550B2 (en) 2002-11-14 2007-09-20 siRNA targeting myeloid cell leukemia sequence 1
US11/974,610 Abandoned US20080091001A1 (en) 2002-11-14 2007-10-15 Functional and hyperfunctional siRNA directed against Bcl-2
US11/974,878 Abandoned US20080114162A1 (en) 2002-11-14 2007-10-16 Functional and hyperfunctional siRNA directed against Bcl-2
US11/974,865 Abandoned US20080091002A1 (en) 2002-11-14 2007-10-16 Functional and hyperfunctional siRNA directed against Bcl-2
US11/974,880 Abandoned US20080091003A1 (en) 2002-11-14 2007-10-16 Functional and hyperfunctional siRNA directed against Bcl-2
US11/974,885 Expired - Lifetime US7511132B2 (en) 2002-11-14 2007-10-16 Functional and hyperfunctional siRNA directed against Bcl-2
US11/975,152 Expired - Fee Related US7795420B2 (en) 2002-11-14 2007-10-17 Functional and hyperfunctional siRNA directed against Bcl-2
US11/975,331 Abandoned US20080091004A1 (en) 2002-11-14 2007-10-18 Functional and hyperfunctional siRNA directed against Bcl-2
US11/975,661 Abandoned US20080108803A1 (en) 2002-11-14 2007-10-19 Functional and hyperfunctional siRNA directed against Bcl-2
US12/157,137 Expired - Lifetime US7642349B2 (en) 2002-11-14 2008-06-06 siRNA targeting TATA box binding protein (TBP)-associated factor (TAF1)
US12/287,757 Expired - Fee Related US7576196B2 (en) 2002-11-14 2008-10-14 siRNA targeting transducin (beta)-like 3 (TBL3)
US12/330,981 Expired - Fee Related US7576197B2 (en) 2002-11-14 2008-12-09 SiRNA targeting KRAS
US12/322,980 Abandoned US20090163701A1 (en) 2002-11-14 2009-02-10 siRNA targeting tumor necrosis factor receptor superfamily member 1A
US12/378,164 Expired - Fee Related US7592444B2 (en) 2002-11-14 2009-02-11 siRNA targeting myeloid cell leukemia sequence 1
US12/384,768 Expired - Lifetime US8030474B2 (en) 2002-11-14 2009-04-08 siRNA targeting cyclin-dependent kinase 4 (CDK4)
US12/459,489 Abandoned US20090291497A1 (en) 2002-11-14 2009-07-01 siRNA targeting transducin (beta)-like 3 (TBL3)
US12/459,670 Expired - Fee Related US7745611B2 (en) 2002-11-14 2009-07-06 siRNA targeting KRAS
US12/463,000 Abandoned US20100004142A1 (en) 2002-11-14 2009-08-12 siRNA targeting myeloid cell Leukemia sequence 1
US12/584,705 Expired - Fee Related US7807819B2 (en) 2002-11-14 2009-09-10 siRNA targeting survivin
US12/590,707 Expired - Lifetime US7803933B2 (en) 2002-11-14 2009-11-12 siRNA targeting TATA box binding protein (TBP)-associated factor (TAF1)
US12/592,335 Expired - Lifetime US7893247B2 (en) 2002-11-14 2009-11-23 siRNA targeting spleen tyrosine kinase
US12/657,263 Abandoned US20100152064A1 (en) 2002-11-14 2010-01-15 siRNA targeting BCL2L1
US12/799,844 Expired - Fee Related US8008474B2 (en) 2002-11-14 2010-05-03 siRNA targeting KRAS
US12/802,647 Expired - Lifetime US8000902B2 (en) 2002-11-14 2010-06-11 Methods and compositions for selecting siRNA of improved functionality
US12/806,320 Expired - Lifetime US7985854B2 (en) 2002-11-14 2010-08-10 siRNA targeting TATA box binding protein (TBP)-associated factor (TAF1)
US12/806,513 Abandoned US20100331214A1 (en) 2002-11-14 2010-08-13 siRNA Targeting Survivin
US12/928,190 Expired - Fee Related US8093370B2 (en) 2002-11-14 2010-12-06 siRNA targeting spleen tyrosine kinase
US13/199,001 Abandoned US20110319474A1 (en) 2002-11-14 2011-08-17 siRNA targeting cyclin-dependent kinase 4 (CDK4)
US13/373,956 Abandoned US20120135892A1 (en) 2002-11-14 2011-12-06 siRNA targeting spleen tyrosine kinase
US16/292,513 Abandoned US20190345573A1 (en) 2002-11-14 2019-03-05 Methods and Compositions for Selecting siRNA of Improved Functionality

Country Status (9)

Country Link
US (52) US8090542B2 (en)
EP (7) EP1560931B1 (en)
JP (2) JP2006507841A (en)
AT (1) ATE517992T1 (en)
AU (1) AU2003295600A1 (en)
DK (1) DK2284266T3 (en)
ES (1) ES2440284T3 (en)
PT (1) PT2284266E (en)
WO (1) WO2004045543A2 (en)

Cited By (88)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060004398A1 (en) * 2004-07-02 2006-01-05 Binder Lawrence J Jr Sequential dilator system
US20060069384A1 (en) * 2004-09-21 2006-03-30 Daniel Wallaker Instrument for use in a medical simulator
US20070129747A1 (en) * 2005-11-14 2007-06-07 Scapa Flow, Llc Medical dilator system or dilator device
US20080097436A1 (en) * 2006-04-21 2008-04-24 Culbert Brad S Method and apparatus for spinal fixation
US20080294172A1 (en) * 2007-05-23 2008-11-27 Rainer Baumgart Instrument set for minimally invasive preparation for bone nailing
WO2009147527A2 (en) 2008-05-26 2009-12-10 Rudolf Morgernstern Lopez Intervertebral implant and installation tool
US20110004222A1 (en) * 2009-04-07 2011-01-06 Lutz Biedermann Tool for Use with a Bone Anchor, in Particular for Spinal Surgery
USD631962S1 (en) 2006-11-14 2011-02-01 Scapa Flow, Llc Medical dilator
US20110144687A1 (en) * 2009-12-10 2011-06-16 Kleiner Jeffrey Lateral Based Retractor System
US8043343B2 (en) 2007-06-28 2011-10-25 Zimmer Spine, Inc. Stabilization system and method
US8109977B2 (en) 2002-07-19 2012-02-07 Interventional Spine, Inc. Method and apparatus for spinal fixation
US8221396B2 (en) 2009-08-27 2012-07-17 Silver Bullet Therapeutics, Inc. Bone implants for the treatment of infection
WO2012102842A1 (en) * 2011-01-28 2012-08-02 Laser Spine Surgical Center, LLC Foraminoplasty device
USD666294S1 (en) * 2002-06-26 2012-08-28 Nuvasive, Inc. Dilator
US8430813B2 (en) 2006-05-26 2013-04-30 Depuy Spine, Inc. Illuminated surgical access system including a surgical access device and integrated light emitter
US20140171946A1 (en) * 2012-12-14 2014-06-19 Warsaw Orthopedic, Inc. Surgical instrument and method
US8771323B2 (en) 2010-11-12 2014-07-08 Silver Bullet Therapeutics, Inc. Bone implant and systems that controllably releases silver
US8927004B1 (en) 2014-06-11 2015-01-06 Silver Bullet Therapeutics, Inc. Bioabsorbable substrates and systems that controllably release antimicrobial metal ions
US20150094610A1 (en) * 2011-03-10 2015-04-02 Interventional Spine, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US20150112398A1 (en) * 2011-03-10 2015-04-23 Interventional Spine, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US9114197B1 (en) 2014-06-11 2015-08-25 Silver Bullett Therapeutics, Inc. Coatings for the controllable release of antimicrobial metal ions
US9277928B2 (en) 2013-03-11 2016-03-08 Interventional Spine, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US9387009B2 (en) 2007-10-05 2016-07-12 DePuy Synthes Products, Inc. Dilation system and method of using the same
US9452242B2 (en) 2014-06-11 2016-09-27 Silver Bullet Therapeutics, Inc. Enhancement of antimicrobial silver, silver coatings, or silver platings
US9522028B2 (en) 2013-07-03 2016-12-20 Interventional Spine, Inc. Method and apparatus for sacroiliac joint fixation
US9522070B2 (en) 2013-03-07 2016-12-20 Interventional Spine, Inc. Intervertebral implant
US20170000627A1 (en) * 2015-06-30 2017-01-05 Mark M Levy Tool for intervertebral cage
US9821094B2 (en) 2014-06-11 2017-11-21 Silver Bullet Therapeutics, Inc. Coatings for the controllable release of antimicrobial metal ions
US9839530B2 (en) 2007-06-26 2017-12-12 DePuy Synthes Products, Inc. Highly lordosed fusion cage
US9883951B2 (en) 2012-08-30 2018-02-06 Interventional Spine, Inc. Artificial disc
US9895236B2 (en) 2010-06-24 2018-02-20 DePuy Synthes Products, Inc. Enhanced cage insertion assembly
US9913727B2 (en) 2015-07-02 2018-03-13 Medos International Sarl Expandable implant
US9924979B2 (en) 2014-09-09 2018-03-27 Medos International Sarl Proximal-end securement of a minimally invasive working channel
US9931223B2 (en) 2008-04-05 2018-04-03 DePuy Synthes Products, Inc. Expandable intervertebral implant
US9980737B2 (en) 2014-08-04 2018-05-29 Medos International Sarl Flexible transport auger
US9993349B2 (en) 2002-06-27 2018-06-12 DePuy Synthes Products, Inc. Intervertebral disc
US9993353B2 (en) 2013-03-14 2018-06-12 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US10058433B2 (en) 2012-07-26 2018-08-28 DePuy Synthes Products, Inc. Expandable implant
US20180271574A1 (en) * 2017-03-22 2018-09-27 Benvenue Medical, Inc. Minimal Impact Access System To Disc Space
US10111712B2 (en) 2014-09-09 2018-10-30 Medos International Sarl Proximal-end securement of a minimally invasive working channel
US10264959B2 (en) 2014-09-09 2019-04-23 Medos International Sarl Proximal-end securement of a minimally invasive working channel
US10265435B2 (en) 2009-08-27 2019-04-23 Silver Bullet Therapeutics, Inc. Bone implant and systems and coatings for the controllable release of antimicrobial metal ions
US10299838B2 (en) 2016-02-05 2019-05-28 Medos International Sarl Method and instruments for interbody fusion and posterior fixation through a single incision
US10390963B2 (en) 2006-12-07 2019-08-27 DePuy Synthes Products, Inc. Intervertebral implant
US10398563B2 (en) 2017-05-08 2019-09-03 Medos International Sarl Expandable cage
US10433977B2 (en) 2008-01-17 2019-10-08 DePuy Synthes Products, Inc. Expandable intervertebral implant and associated method of manufacturing the same
US10500062B2 (en) 2009-12-10 2019-12-10 DePuy Synthes Products, Inc. Bellows-like expandable interbody fusion cage
US10537436B2 (en) 2016-11-01 2020-01-21 DePuy Synthes Products, Inc. Curved expandable cage
US10548741B2 (en) 2010-06-29 2020-02-04 DePuy Synthes Products, Inc. Distractible intervertebral implant
US10682130B2 (en) 2015-09-04 2020-06-16 Medos International Sarl Surgical access port stabilization
US10786264B2 (en) 2015-03-31 2020-09-29 Medos International Sarl Percutaneous disc clearing device
US10888433B2 (en) 2016-12-14 2021-01-12 DePuy Synthes Products, Inc. Intervertebral implant inserter and related methods
US10940016B2 (en) 2017-07-05 2021-03-09 Medos International Sarl Expandable intervertebral fusion cage
USRE48534E1 (en) 2012-04-16 2021-04-27 DePuy Synthes Products, Inc. Detachable dilator blade
US11013530B2 (en) 2019-03-08 2021-05-25 Medos International Sarl Surface features for device retention
US11045324B2 (en) 2006-12-08 2021-06-29 DePuy Synthes Products, Inc. Method of implanting a curable implant material
US11051862B2 (en) 2001-11-03 2021-07-06 DePuy Synthes Products, Inc. Device for straightening and stabilizing the vertebral column
US11129727B2 (en) 2019-03-29 2021-09-28 Medos International Sari Inflatable non-distracting intervertebral implants and related methods
US11134987B2 (en) 2011-10-27 2021-10-05 DePuy Synthes Products, Inc. Method and devices for a sub-splenius/supra-levator scapulae surgical access technique
US11219439B2 (en) 2012-09-26 2022-01-11 DePuy Synthes Products, Inc. NIR/RED light for lateral neuroprotection
US11224453B2 (en) 2014-07-08 2022-01-18 Spinal Elements, Inc. Apparatus and methods for disrupting intervertebral disc tissue
US11241252B2 (en) 2019-03-22 2022-02-08 Medos International Sarl Skin foundation access portal
US11344424B2 (en) 2017-06-14 2022-05-31 Medos International Sarl Expandable intervertebral implant and related methods
US11426286B2 (en) 2020-03-06 2022-08-30 Eit Emerging Implant Technologies Gmbh Expandable intervertebral implant
US11426290B2 (en) 2015-03-06 2022-08-30 DePuy Synthes Products, Inc. Expandable intervertebral implant, system, kit and method
US11439380B2 (en) 2015-09-04 2022-09-13 Medos International Sarl Surgical instrument connectors and related methods
US11446156B2 (en) 2018-10-25 2022-09-20 Medos International Sarl Expandable intervertebral implant, inserter instrument, and related methods
US11452607B2 (en) 2010-10-11 2022-09-27 DePuy Synthes Products, Inc. Expandable interspinous process spacer implant
US11471145B2 (en) 2018-03-16 2022-10-18 Spinal Elements, Inc. Articulated instrumentation and methods of using the same
US11510788B2 (en) 2016-06-28 2022-11-29 Eit Emerging Implant Technologies Gmbh Expandable, angularly adjustable intervertebral cages
US11559328B2 (en) 2015-09-04 2023-01-24 Medos International Sarl Multi-shield spinal access system
US11564811B2 (en) 2015-02-06 2023-01-31 Spinal Elements, Inc. Graft material injector system and method
US11583327B2 (en) 2018-01-29 2023-02-21 Spinal Elements, Inc. Minimally invasive interbody fusion
US11596523B2 (en) 2016-06-28 2023-03-07 Eit Emerging Implant Technologies Gmbh Expandable and angularly adjustable articulating intervertebral cages
US11612491B2 (en) 2009-03-30 2023-03-28 DePuy Synthes Products, Inc. Zero profile spinal fusion cage
US11660082B2 (en) 2011-11-01 2023-05-30 DePuy Synthes Products, Inc. Dilation system
US11672562B2 (en) 2015-09-04 2023-06-13 Medos International Sarl Multi-shield spinal access system
US11744447B2 (en) 2015-09-04 2023-09-05 Medos International Surgical visualization systems and related methods
US11752009B2 (en) 2021-04-06 2023-09-12 Medos International Sarl Expandable intervertebral fusion cage
US11771517B2 (en) 2021-03-12 2023-10-03 Medos International Sarl Camera position indication systems and methods
US11813026B2 (en) 2019-04-05 2023-11-14 Medos International Sarl Systems, devices, and methods for providing surgical trajectory guidance
US11850160B2 (en) 2021-03-26 2023-12-26 Medos International Sarl Expandable lordotic intervertebral fusion cage
US11911287B2 (en) 2010-06-24 2024-02-27 DePuy Synthes Products, Inc. Lateral spondylolisthesis reduction cage
USRE49973E1 (en) 2013-02-28 2024-05-21 DePuy Synthes Products, Inc. Expandable intervertebral implant, system, kit and method
USRE49994E1 (en) 2013-03-14 2024-06-04 Spinal Elements, Inc. Spinal fusion implants and devices and methods for deploying such implants
US12090064B2 (en) 2022-03-01 2024-09-17 Medos International Sarl Stabilization members for expandable intervertebral implants, and related systems and methods
US12150636B2 (en) 2015-09-04 2024-11-26 Medos International Sárl Surgical instrument connectors and related methods
US12427031B2 (en) 2022-08-08 2025-09-30 Medos International Sarl Expandable cage

Families Citing this family (1347)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050053976A1 (en) * 1996-06-06 2005-03-10 Baker Brenda F. Chimeric oligomeric compounds and their use in gene modulation
US5898031A (en) * 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
EP1080226A4 (en) * 1998-05-21 2004-04-21 Isis Pharmaceuticals Inc COMPOSITIONS AND METHODS FOR TOPICAL ADMINISTRATION OF OLIGONUCLEOTIDES
DE19956568A1 (en) 1999-01-30 2000-08-17 Roland Kreutzer Method and medicament for inhibiting the expression of a given gene
US7098192B2 (en) * 1999-04-08 2006-08-29 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of STAT3 expression
PT1176195E (en) * 1999-04-09 2013-07-18 Kyowa Hakko Kirin Co Ltd Method for controlling the activity of immunologically functional molecule
US20040157327A1 (en) * 1999-10-22 2004-08-12 Wyeth Pablo, a polypeptide that interacts with BCL-XL, and uses related thereto
DE10100586C1 (en) 2001-01-09 2002-04-11 Ribopharma Ag Inhibiting gene expression in cells, useful for e.g. treating tumors, by introducing double-stranded complementary oligoRNA having unpaired terminal bases
BR0107536A (en) 2000-03-30 2004-03-02 Whitehead Biomedical Inst Isolated rna, soluble extract, method for producing rna from about 21 to about 23 nucleotides in length; isolated dna
US6946292B2 (en) 2000-10-06 2005-09-20 Kyowa Hakko Kogyo Co., Ltd. Cells producing antibody compositions with increased antibody dependent cytotoxic activity
WO2002044321A2 (en) 2000-12-01 2002-06-06 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Rna interference mediating small rna molecules
US8546143B2 (en) 2001-01-09 2013-10-01 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of a target gene
US7767802B2 (en) * 2001-01-09 2010-08-03 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of anti-apoptotic genes
US7423142B2 (en) 2001-01-09 2008-09-09 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of anti-apoptotic genes
WO2002092616A1 (en) * 2001-05-11 2002-11-21 Orasense, Ltd. Antisense permeation enhancers
US20050164968A1 (en) * 2001-05-18 2005-07-28 Sirna Therapeutics, Inc. RNA interference mediated inhibition of ADAM33 gene expression using short interfering nucleic acid (siNA)
US20050119212A1 (en) * 2001-05-18 2005-06-02 Sirna Therapeutics, Inc. RNA interference mediated inhibition of FAS and FASL gene expression using short interfering nucleic acid (siNA)
US20070173473A1 (en) * 2001-05-18 2007-07-26 Sirna Therapeutics, Inc. RNA interference mediated inhibition of proprotein convertase subtilisin Kexin 9 (PCSK9) gene expression using short interfering nucleic acid (siNA)
US20050196767A1 (en) * 2001-05-18 2005-09-08 Sirna Therapeutics, Inc. RNA interference mediated inhibition of GRB2 associated binding protein (GAB2) gene expression using short interfering nucleic acis (siNA)
WO2008030239A1 (en) * 2006-09-05 2008-03-13 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF HISTONE DEACETYLASE (HDAC) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20050019915A1 (en) * 2001-06-21 2005-01-27 Bennett C. Frank Antisense modulation of superoxide dismutase 1, soluble expression
US20030144221A1 (en) * 2001-07-17 2003-07-31 Isis Pharmaceuticals Inc. Antisense modulation of BCL2-associated X protein expression
US7425545B2 (en) * 2001-07-25 2008-09-16 Isis Pharmaceuticals, Inc. Modulation of C-reactive protein expression
US20050043256A1 (en) * 2001-07-30 2005-02-24 Isis Pharmaceuticals, Inc. Antisense modulation of stearoyl-CoA desaturase expression
US7442781B2 (en) * 2001-08-16 2008-10-28 Urifer Ltd. Diagnosis, prevention and treatment of cancer
US20060009409A1 (en) 2002-02-01 2006-01-12 Woolf Tod M Double-stranded oligonucleotides
EP2221377B2 (en) 2002-02-01 2017-05-17 Life Technologies Corporation Oligonucleotide compositions with enhanced efficiency
EP1572902B1 (en) 2002-02-01 2014-06-11 Life Technologies Corporation HIGH POTENCY siRNAS FOR REDUCING THE EXPRESSION OF TARGET GENES
US7405292B2 (en) * 2002-02-19 2008-07-29 The Children's Hospital Of Philadelphia Cellular genes regulated by HIV-1 infection and methods of use thereof
US8067575B2 (en) * 2002-02-20 2011-11-29 Merck, Sharp & Dohme Corp. RNA interference mediated inhibition of cyclin D1 gene expression using short interfering nucleic acid (siNA)
US7662952B2 (en) * 2002-02-20 2010-02-16 Sirna Therapeutics, Inc. RNA interference mediated inhibition of GRB2 associated binding protein (GAB2) gene expression using short interfering nucleic acid (siNA)
MXPA04010283A (en) * 2002-04-18 2005-08-18 Acuity Pharmaceuticals Inc Means and methods for the specific modulation of target genes in the cns and the eye and methods for their identification.
US7199107B2 (en) 2002-05-23 2007-04-03 Isis Pharmaceuticals, Inc. Antisense modulation of kinesin-like 1 expression
US20040248094A1 (en) * 2002-06-12 2004-12-09 Ford Lance P. Methods and compositions relating to labeled RNA molecules that reduce gene expression
US7148342B2 (en) * 2002-07-24 2006-12-12 The Trustees Of The University Of Pennyslvania Compositions and methods for sirna inhibition of angiogenesis
CA2493949C (en) * 2002-07-26 2015-06-02 Chiron Corporation Modified small interfering rna molecules and methods of use
US20080274989A1 (en) 2002-08-05 2008-11-06 University Of Iowa Research Foundation Rna Interference Suppression of Neurodegenerative Diseases and Methods of Use Thereof
US8729036B2 (en) 2002-08-07 2014-05-20 University Of Massachusetts Compositions for RNA interference and methods of use thereof
US20040029275A1 (en) * 2002-08-10 2004-02-12 David Brown Methods and compositions for reducing target gene expression using cocktails of siRNAs or constructs expressing siRNAs
KR101238701B1 (en) * 2002-08-21 2013-03-05 더 유니버시티 오브 브리티쉬 콜롬비아 RNAi Probes Targeting Cancer-Related Proteins
PT1534340E (en) 2002-09-06 2012-03-13 Cerulean Pharma Inc Cyclodextrin-based polymers for delivering the therapeutic agents covalently bound thereto
AU2003278957A1 (en) 2002-09-26 2004-04-23 Amgen, Inc. Modulation of forkhead box o1a expression
US20060160759A1 (en) * 2002-09-28 2006-07-20 Jianzhu Chen Influenza therapeutic
US20050259483A1 (en) * 2002-09-30 2005-11-24 Oncotherapy Science, Inc. Genes and polypeptides relating to prostate cancers
US7892793B2 (en) * 2002-11-04 2011-02-22 University Of Massachusetts Allele-specific RNA interference
US9827263B2 (en) 2002-11-05 2017-11-28 Ionis Pharmaceuticals, Inc. 2′-methoxy substituted oligomeric compounds and compositions for use in gene modulations
WO2004044170A2 (en) * 2002-11-13 2004-05-27 Metabolex, Inc. A pancreatic islet transcription factor and uses thereof
US20060009410A1 (en) * 2002-11-13 2006-01-12 Crooke Rosanne M Effects of apolipoprotein B inhibition on gene expression profiles in animals
US7511131B2 (en) 2002-11-13 2009-03-31 Genzyme Corporation Antisense modulation of apolipoprotein B expression
US7592442B2 (en) * 2002-11-14 2009-09-22 Dharmacon, Inc. siRNA targeting ribonucleotide reductase M2 polypeptide (RRM2 or RNR-R2)
US7781575B2 (en) 2002-11-14 2010-08-24 Dharmacon, Inc. siRNA targeting tumor protein 53 (p53)
US7612196B2 (en) 2002-11-14 2009-11-03 Dharmacon, Inc. siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B)
US20100113307A1 (en) * 2002-11-14 2010-05-06 Dharmacon, Inc. siRNA targeting vascular endothelial growth factor (VEGF)
US7951935B2 (en) 2002-11-14 2011-05-31 Dharmacon, Inc. siRNA targeting v-myc myelocytomatosis viral oncogene homolog (MYC)
US9771586B2 (en) 2002-11-14 2017-09-26 Thermo Fisher Scientific Inc. RNAi targeting ZNF205
US7635770B2 (en) * 2002-11-14 2009-12-22 Dharmacon, Inc. siRNA targeting protein kinase N-3 (PKN-3)
US9719092B2 (en) 2002-11-14 2017-08-01 Thermo Fisher Scientific Inc. RNAi targeting CNTD2
US10011836B2 (en) 2002-11-14 2018-07-03 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
WO2006006948A2 (en) 2002-11-14 2006-01-19 Dharmacon, Inc. METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY
US9719094B2 (en) 2002-11-14 2017-08-01 Thermo Fisher Scientific Inc. RNAi targeting SEC61G
US7619081B2 (en) * 2002-11-14 2009-11-17 Dharmacon, Inc. siRNA targeting coatomer protein complex, subunit beta 2 (COPB2)
US7691998B2 (en) * 2002-11-14 2010-04-06 Dharmacon, Inc. siRNA targeting nucleoporin 62kDa (Nup62)
US20090227780A1 (en) * 2002-11-14 2009-09-10 Dharmacon, Inc. siRNA targeting connexin 43
US9839649B2 (en) 2002-11-14 2017-12-12 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US9879266B2 (en) 2002-11-14 2018-01-30 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
US20080268457A1 (en) * 2002-11-14 2008-10-30 Dharmacon, Inc. siRNA targeting forkhead box P3 (FOXP3)
US8198427B1 (en) 2002-11-14 2012-06-12 Dharmacon, Inc. SiRNA targeting catenin, beta-1 (CTNNB1)
US7977471B2 (en) * 2002-11-14 2011-07-12 Dharmacon, Inc. siRNA targeting TNFα
EP1560931B1 (en) 2002-11-14 2011-07-27 Dharmacon, Inc. Functional and hyperfunctional sirna
US9228186B2 (en) 2002-11-14 2016-01-05 Thermo Fisher Scientific Inc. Methods and compositions for selecting siRNA of improved functionality
CN1742086B (en) * 2002-11-22 2010-05-12 生物智囊团株式会社 Method for searching target base sequence of RNA interference
US7605249B2 (en) 2002-11-26 2009-10-20 Medtronic, Inc. Treatment of neurodegenerative disease through intracranial delivery of siRNA
US7829694B2 (en) 2002-11-26 2010-11-09 Medtronic, Inc. Treatment of neurodegenerative disease through intracranial delivery of siRNA
US7618948B2 (en) 2002-11-26 2009-11-17 Medtronic, Inc. Devices, systems and methods for improving and/or cognitive function through brain delivery of siRNA
US20060257851A1 (en) * 2002-11-26 2006-11-16 Itzhak Bentwich Bioinformatically detectable group of novel viral regulatory genes and uses thereof
US20040231909A1 (en) * 2003-01-15 2004-11-25 Tai-Yang Luh Motorized vehicle having forward and backward differential structure
JP3792655B2 (en) * 2003-01-20 2006-07-05 日本電気株式会社 Novel oncogene, recombinant protein derived from the oncogene, and uses thereof
US7732591B2 (en) * 2003-11-25 2010-06-08 Medtronic, Inc. Compositions, devices and methods for treatment of huntington's disease through intracranial delivery of sirna
US7994149B2 (en) 2003-02-03 2011-08-09 Medtronic, Inc. Method for treatment of Huntington's disease through intracranial delivery of sirna
WO2004071453A2 (en) 2003-02-13 2004-08-26 Isis Pharmaceuticals, Inc. Compositions and methods for treatment of pouchitis
WO2004076664A2 (en) * 2003-02-21 2004-09-10 University Of South Florida Vectors for regulating gene expression
AU2004217437B2 (en) * 2003-03-05 2009-11-19 Senesco Technologies, Inc. Use of antisense oligonucleotides or siRNA to suppress expression of eIF-5A1
EP1605961A4 (en) * 2003-03-12 2009-11-11 Vasgene Therapeutics Inc Polypeptide compounds for inhibiting angiogenesis and tumor growth
AU2003225410A1 (en) 2003-03-21 2004-10-11 Academisch Ziekenhuis Leiden Modulation of exon recognition in pre-mrna by interfering with the secondary rna structure
US20040185559A1 (en) * 2003-03-21 2004-09-23 Isis Pharmaceuticals Inc. Modulation of diacylglycerol acyltransferase 1 expression
WO2004100977A1 (en) * 2003-03-25 2004-11-25 The Board Of Trustees Of The University Of Illinois Inhibition of tumor cell proliferation by foxm1b inhibitors
EP1469070A1 (en) * 2003-04-15 2004-10-20 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Livin-specific siRNAs for the treatment of therapy-resistant tumors
WO2004094606A2 (en) * 2003-04-18 2004-11-04 The Trustees Of The University Of Pennsylvania COMPOSITIONS AND METHODS FOR siRNA INHIBITION OF ANGIOPOIETIN 1 AND 2 AND THEIR RECEPTOR TIE2
KR20060063788A (en) * 2003-05-30 2006-06-12 니뽄 신야쿠 가부시키가이샤 Oligonucleotide Support Complex, Pharmaceutical Composition Containing the Complex
US20080020990A1 (en) * 2003-05-30 2008-01-24 Nippon Shinyaku Co., Ltd. Oligo Double-Stranded Rna Inhibiting the Expression of Bcl-2 and Pharmaceutical Composition Containing the Same
PL1633767T3 (en) * 2003-06-02 2019-07-31 University Of Massachusetts Methods and compositions for controlling efficacy of rna silencing
ATE485394T1 (en) * 2003-06-02 2010-11-15 Univ Massachusetts METHODS AND COMPOSITIONS FOR IMPROVING THE EFFECTIVENESS AND SPECIFICITY OF FNAI
US7750144B2 (en) * 2003-06-02 2010-07-06 University Of Massachusetts Methods and compositions for enhancing the efficacy and specificity of RNA silencing
JP4716517B2 (en) * 2003-06-09 2011-07-06 アルナイラム ファーマシューティカルズ， インコーポレイテッド Methods for treating neurodegenerative diseases
US7595306B2 (en) * 2003-06-09 2009-09-29 Alnylam Pharmaceuticals Inc Method of treating neurodegenerative disease
US8575327B2 (en) 2003-06-12 2013-11-05 Alnylam Pharmaceuticals, Inc. Conserved HBV and HCV sequences useful for gene silencing
US7479546B2 (en) * 2003-06-27 2009-01-20 Diadexus, Inc. Pro104 antibody compositions and methods of use
WO2005020888A2 (en) * 2003-07-02 2005-03-10 Saint Louis University Compositions and methods of treating and diagnosing hepatoma
FR2857013B1 (en) * 2003-07-02 2005-09-30 Commissariat Energie Atomique SMALL INTERFERING RNA SPECIFIC OF ALPHA, ALPHA PRIME AND BETA SUBUNITS OF PROTEIN KINASE CK2 AND THEIR APPLICATIONS
US7173015B2 (en) * 2003-07-03 2007-02-06 The Trustees Of The University Of Pennsylvania Inhibition of Syk kinase expression
SG145713A1 (en) * 2003-08-13 2008-09-29 Univ Illinois SILENCING OF TGFss TYPE II RECEPTOR EXPRESSION BY SIRNA
US7888497B2 (en) * 2003-08-13 2011-02-15 Rosetta Genomics Ltd. Bioinformatically detectable group of novel regulatory oligonucleotides and uses thereof
US7825235B2 (en) * 2003-08-18 2010-11-02 Isis Pharmaceuticals, Inc. Modulation of diacylglycerol acyltransferase 2 expression
EP1666593A4 (en) * 2003-08-18 2009-07-15 Japan Health Science Found IMPROVED siRNA MOLECULES AND TECHNIQUE FOR INHIBITING GENE EXPRESSION USING THE SAME
US8501705B2 (en) * 2003-09-11 2013-08-06 The Board Of Regents Of The University Of Texas System Methods and materials for treating autoimmune and/or complement mediated diseases and conditions
ATE557087T1 (en) * 2003-09-11 2012-05-15 Hubit Genomix Inc Procedure and KIT for the detection of sclerosis proliferative diseases and/or remedies against sclerosis proliferative diseases as well as procedures and KIT to identify proliferative diseases caused by the prevention and/or treatment of sclerosis.
US8680063B2 (en) 2003-09-12 2014-03-25 University Of Massachusetts RNA interference for the treatment of gain-of-function disorders
CA2579638C (en) * 2003-09-12 2016-04-19 University Of Massachusetts Rna interference targeting non-disease causing single nucleotide polymorphisms within a gene encoding a gain-of-function mutant huntingtin protein
CN100558893C (en) 2003-09-18 2009-11-11 Isis药物公司 Regulation of eIF4E expression
WO2005037303A1 (en) * 2003-09-22 2005-04-28 Board Of Trustees Of The University Of Illinois Methods and compositions of ig20 and denn-sv splice variants
WO2005028675A2 (en) * 2003-09-24 2005-03-31 Oncotherapy Science, Inc. Methods for detecting, diagnosing and treating hepatocellular carcinomas (hcc)
AR041407A1 (en) * 2003-09-26 2005-05-18 Nestor Alberto Kerner OLIGONUCLEOTIDOS ANTIANDROGENOS USABLE IN THE TREATMENT OF DERMATOLOGICAL PATHOLOGIES RELATED TO THE ANDROGEN METABOLISM, ITS PHARMACEUTICAL COMPOSITIONS AND THEIR USES AND METHODS OF TREATMENT
WO2005038013A1 (en) 2003-10-07 2005-04-28 Isis Pharmaceuticals, Inc. Artisense oligonucleotides optimized for kidney targeting
JP4486928B2 (en) * 2003-10-09 2010-06-23 タカラバイオ株式会社 Composition for suppressing the function of human Flt3
WO2005042719A2 (en) * 2003-10-30 2005-05-12 The Cbr Institute For Biomedical Research, Inc. Methods for treating and preventing ischemia-reperfusion injury using rna interfering agents
US20050191653A1 (en) * 2003-11-03 2005-09-01 Freier Susan M. Modulation of SGLT2 expression
WO2005056021A1 (en) 2003-12-04 2005-06-23 University Of South Florida Polynucleotides for reducing respiratory syncytial virus gene expression
SE0303397D0 (en) * 2003-12-17 2003-12-17 Index Pharmaceuticals Ab Compounds and method for RNA interference
US20060134787A1 (en) 2004-12-22 2006-06-22 University Of Massachusetts Methods and compositions for enhancing the efficacy and specificity of single and double blunt-ended siRNA
EP1715896A4 (en) * 2004-01-12 2009-01-07 Lorus Therapeutics Inc ANTISENSE OLIGONUCLEOTIDES AGAINST RIBONUCLEOTIDE REDUCTASE R2 AND ITS USE IN COMBINATION THERAPIES FOR THE TREATMENT OF CANCER
EP1778858A4 (en) * 2004-01-15 2009-08-19 Univ Washington HIGH PERFORMANCE PHARMACEUTICAL SCREENING USING DROSOPHILES
US20070161586A1 (en) * 2004-01-16 2007-07-12 Takeda Pharmaceutical Company Limited Drug for preventing and treating atherosclerosis
EP2363480A3 (en) * 2004-01-20 2015-10-07 Isis Pharmaceuticals, Inc. Modulation of glucocorticoid receptor expression
US8778900B2 (en) * 2004-01-22 2014-07-15 Isis Pharmaceuticals, Inc. Modulation of eIF4E-BP1 expression
US7468431B2 (en) * 2004-01-22 2008-12-23 Isis Pharmaceuticals, Inc. Modulation of eIF4E-BP2 expression
US20050203043A1 (en) * 2004-01-23 2005-09-15 Dharmacon, Inc. Identification of toxic nucleotide sequences
US8491914B2 (en) * 2004-02-13 2013-07-23 Ibc Pharmaceuticals, Inc. Dock-and-lock (DNL) complexes for delivery of interference RNA
US7772389B2 (en) 2004-02-13 2010-08-10 Rockefeller University Anti-microRNA oligonucleotide molecules
GB0404209D0 (en) * 2004-02-25 2004-03-31 Uws Ventures Ltd Materials and methods for treatment of allergic disease
WO2005085443A2 (en) * 2004-03-01 2005-09-15 Massachusetts Institute Of Technology Rnai-based therapeutics for allergic rhinitis and asthma
DE102004010547A1 (en) * 2004-03-03 2005-11-17 Beiersdorf Ag Oligoribonucleotides for the treatment of irritative and / or inflammatory skin conditions by RNA interference
WO2005089224A2 (en) * 2004-03-12 2005-09-29 Alnylam Pharmaceuticals, Inc. iRNA AGENTS TARGETING VEGF
CA2559955C (en) * 2004-03-15 2016-02-16 City Of Hope Methods and compositions for the specific inhibition of gene expression by double-stranded rna
MXPA06010667A (en) * 2004-03-19 2007-07-04 Penn State Res Found Combinatorial methods and compositions for treatment of melanoma.
TW200600785A (en) * 2004-03-23 2006-01-01 Oncotherapy Science Inc Method for diagnosing non-small cell lung cancer
JP2005312428A (en) * 2004-03-31 2005-11-10 Keio Gijuku Treatment of cancer using suppression of Skp-2 expression
KR101147147B1 (en) 2004-04-01 2012-05-25 머크 샤프 앤드 돔 코포레이션 Modified polynucleotides for reducing off-target effects in rna interference
US20050244869A1 (en) * 2004-04-05 2005-11-03 Brown-Driver Vickie L Modulation of transthyretin expression
WO2005097817A2 (en) 2004-04-05 2005-10-20 Alnylam Pharmaceuticals, Inc. Process and reagents for oligonucleotide synthesis and purification
US8088902B2 (en) * 2004-04-05 2012-01-03 The Rockefeller University DNA virus microRNA and methods for inhibiting same
US7416842B2 (en) * 2004-04-05 2008-08-26 The Rockefeller University DNA virus microRNA
KR101234281B1 (en) 2004-04-09 2013-02-18 가부시키가이샤 진케어켄큐쇼 Cancer cell-specific apoptosis-inducing agents that target chromosome stabilization-associated genes
US7365058B2 (en) 2004-04-13 2008-04-29 The Rockefeller University MicroRNA and methods for inhibiting same
WO2005117938A2 (en) * 2004-04-13 2005-12-15 Regents Of The University Of Minnesota Methods of treating ocular conditions
US20050261233A1 (en) * 2004-04-21 2005-11-24 Sanjay Bhanot Modulation of glucose-6-phosphatase translocase expression
EP1737957A1 (en) * 2004-04-22 2007-01-03 Yissum Research Development Company Of The Hebrew University Of Jerusalem UNIVERSAL TARGET SEQUENCES FOR siRNA GENE SILENCING
CA2562833A1 (en) * 2004-04-27 2005-11-03 Galapagos N.V. Methods, agents, and compound screening assays for inducing differentiation of undifferentiated mammalian cells into osteoblasts
US7626014B2 (en) 2004-04-27 2009-12-01 Alnylam Pharmaceuticals Single-stranded and double-stranded oligonucleotides comprising a 2-arylpropyl moiety
EP3034510A1 (en) 2004-04-30 2016-06-22 Alnylam Pharmaceuticals Inc. Oligonucleotides comprising a c5-modified pyrimidine
US20050287558A1 (en) 2004-05-05 2005-12-29 Crooke Rosanne M SNPs of apolipoprotein B and modulation of their expression
US7605250B2 (en) * 2004-05-12 2009-10-20 Dharmacon, Inc. siRNA targeting cAMP-specific phosphodiesterase 4D
JP5697297B2 (en) 2004-05-14 2015-04-08 ロゼッタ ジノミクス リミテッド Micro NAS and its use
WO2005111213A1 (en) * 2004-05-18 2005-11-24 Kurume University Target gene mimitin of myc
US7563885B1 (en) * 2004-05-24 2009-07-21 Isis Pharmaceuticals, Inc. Modulation of Tudor-SN expression
US20100152280A1 (en) * 2004-05-24 2010-06-17 Isis Pharmaceuticals, Inc. Modulation of sid-1 expression
US8101350B1 (en) * 2004-05-24 2012-01-24 Isis Pharmaceuticals, Inc. Modulation of exportin 5 expression
US7795419B2 (en) * 2004-05-26 2010-09-14 Rosetta Genomics Ltd. Viral and viral associated miRNAs and uses thereof
US7575863B2 (en) 2004-05-28 2009-08-18 Applied Biosystems, Llc Methods, compositions, and kits comprising linker probes for quantifying polynucleotides
US20060015264A1 (en) * 2004-06-02 2006-01-19 Mcshea Andrew Interfering stem-loop sequences and method for identifying
EP1765416A4 (en) * 2004-06-03 2010-03-24 Isis Pharmaceuticals Inc DOUBLE-STRANDED COMPOSITIONS COMPRISING DIFFERENTIALLY MODIFIED STRANDS FOR USE IN GENETIC MODULATION
US8394947B2 (en) * 2004-06-03 2013-03-12 Isis Pharmaceuticals, Inc. Positionally modified siRNA constructs
EP1602926A1 (en) 2004-06-04 2005-12-07 University of Geneva Novel means and methods for the treatment of hearing loss and phantom hearing
US7740861B2 (en) 2004-06-16 2010-06-22 University Of Massachusetts Drug delivery product and methods
US8007814B2 (en) 2004-06-16 2011-08-30 University Of Massachusetts Therapy for lysosomal enzyme deficiencies
US20060156421A1 (en) * 2004-06-18 2006-07-13 Cagan Ross L High throughput screening methods for anti-metastatic compounds
JP4852539B2 (en) * 2004-06-22 2012-01-11 ザ・ボード・オブ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・イリノイ Method of inhibiting tumor cell growth by FOXM1 siRNA
US20060051815A1 (en) * 2004-06-25 2006-03-09 The J. David Gladstone Institutes Methods of treating smooth muscle cell disorders
PL1766010T3 (en) 2004-06-28 2011-07-29 Univ Western Australia Antisense oligonucleotides for inducing exon skipping and methods of use thereof
CA2572151A1 (en) 2004-06-30 2006-08-24 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a non-phosphate backbone linkage
JP2006031308A (en) * 2004-07-15 2006-02-02 Mitsubishi Space Software Kk Nucleic acid sequence design device, nucleic acid sequence design method, nucleic acid sequence design program, function inhibition effect calculation device, function inhibition effect calculation method, function inhibition effect calculation program, function inhibition influence degree calculation device, function inhibition influence degree calculation method, and function inhibition effect Degree calculation program.
CA2574086A1 (en) * 2004-07-21 2006-02-23 Medtronic, Inc. Medical devices and methods for reducing localized fibrosis
AU2005328382C1 (en) 2004-07-21 2013-01-24 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a modified or non-natural nucleobase
US7514548B2 (en) * 2004-08-02 2009-04-07 University Of Iowa Research Foundation Methods of inhibiting COX-2
WO2006112872A2 (en) 2004-08-04 2006-10-26 Alnylam Pharmaceuticals, Inc. Oligonucleotides comprising a ligand tethered to a modified or non-natural nucleobase
US20060223147A1 (en) * 2004-08-05 2006-10-05 Kyowa Hakko Kogyo Co., Ltd., Process for producing glycoprotein composition
CN101123994B (en) 2004-08-16 2012-11-14 夸克医药公司 Therapeutic use of inhibitors of RTP801
EP1786905B1 (en) * 2004-08-18 2011-08-03 Lorus Therapeutics Inc. Small interfering rna molecules against ribonucleotide reductase and uses thereof
US20110313024A1 (en) * 2004-08-20 2011-12-22 Leonid Beigelman RNA INTERFERENCE MEDIATED INHIBITION OF PROPROTEIN CONVERTASE SUBTILISIN KEXIN 9 (PCSK9) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
PT1781787T (en) * 2004-08-23 2017-07-17 Sylentis Sau Treatment of eye disorders characterized by an elevated intraocular pressure by sirnas
CN1324136C (en) * 2004-08-24 2007-07-04 暨南大学 siRNA duplex for inhibiting bc1-2 gene expression and its application
CN100410373C (en) * 2004-08-24 2008-08-13 暨南大学 siRNA duplexes inhibiting bcl-2 gene expression
CN100395335C (en) * 2004-08-24 2008-06-18 暨南大学 siRNA duplexes inhibiting bcl-2 gene expression
RU2410430C2 (en) * 2004-08-31 2011-01-27 Силентис С.А.У. Methods and compositions for inhibiting expression of p2x7 receptor
US20060194220A1 (en) * 2004-09-23 2006-08-31 Vasgene Therapeutics, Inc. Compositions and methods for detecting and treating tumors
CN102628044A (en) 2004-09-24 2012-08-08 阿尔尼拉姆医药品有限公司 RNAi modulation of APOB and uses thereof
CN101291948B (en) * 2004-09-28 2012-05-30 夸克医药公司 Oligoribonucleotides and methods for their use in the treatment of hair loss, kidney failure and other diseases
PT1799269T (en) * 2004-09-28 2016-10-04 Quark Pharmaceuticals Inc Oligoribonucleotides and methods of use thereof for treatment of alopecia, acute renal failure and other diseases
CA2580189C (en) * 2004-09-29 2013-05-21 Children's Memorial Hospital Sirna-mediated gene silencing of alpha synuclein
US8765704B1 (en) 2008-02-28 2014-07-01 Novartis Ag Modified small interfering RNA molecules and methods of use
CA2581651C (en) * 2004-10-01 2014-12-16 Novartis Vaccines And Diagnostics, Inc. Cholesterol-labelled modified rna
US7825229B2 (en) * 2005-03-25 2010-11-02 Rosetta Genomics Ltd. Lung cancer-related nucleic acids
US20090186353A1 (en) * 2004-10-04 2009-07-23 Rosetta Genomics Ltd. Cancer-related nucleic acids
WO2006044531A2 (en) * 2004-10-13 2006-04-27 Isis Parmaceuticals, Inc. Antisense modulation of ptp1b expression
US20060110440A1 (en) * 2004-10-22 2006-05-25 Kiminobu Sugaya Method and system for biasing cellular development
US7790878B2 (en) * 2004-10-22 2010-09-07 Alnylam Pharmaceuticals, Inc. RNAi modulation of RSV, PIV and other respiratory viruses and uses thereof
US8080420B2 (en) 2004-10-22 2011-12-20 University Of Central Florida Research Foundation, Inc. Methods and products for biasing cellular development
US20060189564A1 (en) * 2004-10-22 2006-08-24 Medtronic, Inc. Methods and sequences to suppress pro-inflamatory cytokine actions locally to treat pain
AU2005304638A1 (en) * 2004-11-12 2006-05-18 Massachusetts Institute Of Technology Methods and compositions for treating cellular proliferative diseases
US8440610B2 (en) 2004-11-12 2013-05-14 Massachusetts Institute Of Technology Mapkap kinase-2 as a specific target for blocking proliferation of P53-defective cells
AU2005306533B2 (en) * 2004-11-17 2012-05-31 Arbutus Biopharma Corporation siRNA silencing of apolipoprotein B
JP4809240B2 (en) * 2004-11-19 2011-11-09 株式会社ジーンケア研究所 Cancer cell-specific cell growth inhibitor
US7923206B2 (en) 2004-11-22 2011-04-12 Dharmacon, Inc. Method of determining a cellular response to a biological agent
US7923207B2 (en) 2004-11-22 2011-04-12 Dharmacon, Inc. Apparatus and system having dry gene silencing pools
US7935811B2 (en) 2004-11-22 2011-05-03 Dharmacon, Inc. Apparatus and system having dry gene silencing compositions
US8003780B2 (en) * 2004-11-24 2011-08-23 Neomics Co., Ltd. AIMP2-DX2 gene and SiRNA targeting AIMP2-DX2
US9944713B2 (en) 2004-11-24 2018-04-17 Medicinal Bioconvergence Research Center Antibody specific to the AIMP2-DX2
EP2133081B1 (en) * 2004-11-24 2012-01-04 Alnylam Pharmaceuticals Inc. RNAi modulation of the BCR-ABL fusion gene and uses thereof
WO2006063164A2 (en) * 2004-12-08 2006-06-15 Wisconsin Alumni Research Foundation Compositions and methods for treating neuroendocrine tumors
JP4672021B2 (en) 2004-12-08 2011-04-20 バイオニア コーポレイション Method for suppressing expression of target mRNA using siRNA having base sequence complementary to target mRNA
WO2006063168A2 (en) * 2004-12-09 2006-06-15 Centocor, Inc. Oxytocin receptor antagonists and their use for the treatment of pulmonary related diseases
AU2005313883B2 (en) * 2004-12-09 2011-03-31 Alnylam Pharmaceuticals, Inc. Compositions and methods for inducing an immune response in a mammal and methods of avoiding an immune response to oligonucleotide agents such as short interfering RNAs
EP1824872B1 (en) * 2004-12-14 2012-02-08 Alnylam Pharmaceuticals Inc. Rnai modulation of mll-af4 and uses thereof
US7332591B2 (en) * 2004-12-21 2008-02-19 The University Of Iowa Research Foundation Bardet-Biedl susceptibility gene and uses thereof
JP2008525029A (en) * 2004-12-22 2008-07-17 ニュークレオニクス・インコーポレイテッド HBV and HCV conserved sequences useful for gene silencing
TWI401316B (en) * 2004-12-23 2013-07-11 Alcon Inc Rnai inhibition of serum amyloid a for treatment of glaucoma
US20060166920A1 (en) * 2005-12-27 2006-07-27 Regents Of The University Of Michigan Oligonucleotide based therapeutics
EP2230304B1 (en) 2005-01-07 2012-03-28 Alnylam Pharmaceuticals Inc. RNAI modulation of RSV and therapeutic uses thereof
DE102005003788A1 (en) 2005-01-19 2006-07-20 Eberhard-Karls-Universität Tübingen Universitätsklinikum siRNA molecules for the treatment of blood vessels
AU2006209192A1 (en) * 2005-01-24 2006-08-03 Alnylam Pharmaceuticals, Inc. RNAi modulation of the Nogo-L or Nogo-R gene and uses thereof
US7879992B2 (en) * 2005-01-31 2011-02-01 Isis Pharmaceuticals, Inc. Modification of MyD88 splicing using modified oligonucleotides
TW200639252A (en) * 2005-02-01 2006-11-16 Alcon Inc RNAi-mediated inhibition of ocular hypertension targets
US20090016959A1 (en) * 2005-02-18 2009-01-15 Richard Beliveau Delivery of antibodies to the central nervous system
AU2006216514C1 (en) 2005-02-25 2012-09-27 Isis Pharmaceuticals, Inc. Compositions and their uses directed to IL-4R alpha
AU2006219666B2 (en) * 2005-03-02 2011-01-27 National Institute Of Immunology Inhibition of SPAG9 expression with siRNAs
US20070185044A1 (en) * 2005-03-08 2007-08-09 Dobie Kenneth W Modulation of ace2 expression
KR20080018858A (en) 2005-03-11 2008-02-28 알콘, 인코퍼레이티드 RNA-mediated inhibition of fleece-related protein for the treatment of glaucoma
GB0505081D0 (en) * 2005-03-14 2005-04-20 Genomica Sau Downregulation of interleukin-12 expression by means of rnai technology
JP4131271B2 (en) * 2005-03-30 2008-08-13 ソニー株式会社 Information processing apparatus and method, and program
AU2006230436B2 (en) * 2005-03-31 2011-11-24 Calando Pharmaceuticals, Inc. Inhibitors of ribonucleotide reductase subunit 2 and uses thereof
US20070213293A1 (en) * 2005-04-08 2007-09-13 Nastech Pharmaceutical Company Inc. Rnai therapeutic for respiratory virus infection
AU2006235451A1 (en) * 2005-04-08 2006-10-19 Isis Pharmaceuticals, Inc. Compositions and their uses directed to acetyl-CoA carboxylases
US20090117539A1 (en) * 2005-04-12 2009-05-07 Larry Gilbertson DNA sequences for gene suppression
AU2006235489A1 (en) 2005-04-12 2006-10-19 Intradigm Corporation Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases
WO2006112239A1 (en) * 2005-04-15 2006-10-26 National University Corporation Tottori University hTERT GENE EXPRESSION REGULATORY GENE
US20090203055A1 (en) * 2005-04-18 2009-08-13 Massachusetts Institute Of Technology Compositions and methods for RNA interference with sialidase expression and uses thereof
US20060253068A1 (en) * 2005-04-20 2006-11-09 Van Bilsen Paul Use of biocompatible in-situ matrices for delivery of therapeutic cells to the heart
EP1714970A1 (en) * 2005-04-22 2006-10-25 Universität des Saarlandes Use of inhibitors of RNAse A-family enzymes for stabilizing oligonucleotides having RNA interfering activity
US8247543B2 (en) 2005-04-29 2012-08-21 The Rockefeller University Human microRNAs and methods for inhibiting same
US7902352B2 (en) * 2005-05-06 2011-03-08 Medtronic, Inc. Isolated nucleic acid duplex for reducing huntington gene expression
WO2006121960A2 (en) * 2005-05-06 2006-11-16 Medtronic, Inc. Methods and sequences to suppress primate huntington gene expression
KR20060119412A (en) * 2005-05-20 2006-11-24 아주대학교산학협력단 SiRNA for inhibiting IL-6 expression and composition containing same
JP2008541729A (en) * 2005-05-24 2008-11-27 アイシス ファーマシューティカルズ， インコーポレーテッド Regulation of LMW-PTPase expression
EP1728514A1 (en) * 2005-06-03 2006-12-06 Immunotech S.A. Uses of oligonucleotides stimulatory of the mesenchymal stem cell proliferation
US7498137B2 (en) * 2005-06-06 2009-03-03 Gen-Probe Incorporated Compositions and methods for determining the presence of Chlamydophila pneumoniae in a test sample
US20100266574A1 (en) * 2005-06-10 2010-10-21 Orna Mor Oligoribonucleotides and Methods of Use Thereof for Treatment of Fibrotic Conditions and Other Diseases
EP1734118A1 (en) * 2005-06-15 2006-12-20 Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts Identification of JAK/STAT pathway modulating genes by genome wide RNAi screening
FI20050640A0 (en) * 2005-06-16 2005-06-16 Faron Pharmaceuticals Oy Compounds for treating or preventing diseases or disorders related to amine oxidases
EP2644700A1 (en) * 2005-06-23 2013-10-02 Isis Pharmaceuticals, Inc. Compositions and methods for modulation of SMN2 splicing
CA2608964A1 (en) * 2005-06-27 2007-01-04 Alnylam Pharmaceuticals, Inc. Rnai modulation of hif-1 and therapeutic uses thereof
US20080280843A1 (en) * 2006-05-24 2008-11-13 Van Bilsen Paul Methods and kits for linking polymorphic sequences to expanded repeat mutations
US9133517B2 (en) 2005-06-28 2015-09-15 Medtronics, Inc. Methods and sequences to preferentially suppress expression of mutated huntingtin
US20070044161A1 (en) * 2005-07-21 2007-02-22 Juergen Soutschek RNAi modulation of the Rho-A gene in research models
US20090155241A1 (en) * 2005-07-22 2009-06-18 Japanese Foundation For Cancer Research Prophylactic/therapeutic agent for cancer
EP1907582B1 (en) * 2005-07-27 2012-01-04 Oncotherapy Science, Inc. Ect2 as a therapeutic target for esophageal cancer
JP2009502172A (en) * 2005-07-28 2009-01-29 ユニバーシティ オブ マサチューセッツ Glucose transport-related genes, polypeptides, and methods of use thereof
CA2619534A1 (en) * 2005-08-18 2007-02-22 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating neurological disease
US20070111226A1 (en) * 2005-08-24 2007-05-17 Applera Corporation Method to Quantify siRNAs, miRNAs and Polymorphic miRNAs
US20070054873A1 (en) * 2005-08-26 2007-03-08 Protiva Biotherapeutics, Inc. Glucocorticoid modulation of nucleic acid-mediated immune stimulation
EP2270181B1 (en) * 2005-09-16 2015-10-21 deVGen N.V. DSRNA as insect control agent
CN101313066A (en) * 2005-09-19 2008-11-26 强生医药研究及开发有限责任公司 Modulation of glucocorticoid receptor expression
EP1937802A4 (en) * 2005-09-20 2009-06-10 London Health Sci Ct Res Inc USE OF SIRNAS IN SOLUTIONS FOR STORING AND REPERFUSING ORGANS
US20120164730A1 (en) * 2005-10-11 2012-06-28 Ben-Gurion University Of The Negev Research And Development Authority Ltd. Compositions for silencing the expression of vdac1 and uses thereof
WO2007047512A2 (en) * 2005-10-14 2007-04-26 Musc Foundation For Research Development Inhibition of pax2 by defb1 induction as a therapy for cancer
GB0521351D0 (en) * 2005-10-20 2005-11-30 Genomica Sau Modulation of TRPV expression levels
WO2007047913A2 (en) * 2005-10-20 2007-04-26 Isis Pharmaceuticals, Inc Compositions and methods for modulation of lmna expression
CA2624221A1 (en) * 2005-10-24 2007-05-03 Takeda Pharmaceutical Company Limited Preventives/remedies for cancer
GB0521716D0 (en) * 2005-10-25 2005-11-30 Genomica Sau Modulation of 11beta-hydroxysteriod dehydrogenase 1 expression for the treatment of ocular diseases
US7723314B1 (en) * 2005-10-28 2010-05-25 Transderm, Inc. Methods and compositions for treating pachyonychia congenita
CN101365801B (en) 2005-10-28 2013-03-27 阿尔尼拉姆医药品有限公司 Compositions and methods for inhibiting huntingtin gene expression
EP1948680A4 (en) * 2005-10-28 2010-01-13 Univ California METHODS AND COMPOUNDS FOR DETECTION AND ISOLATION OF LYMPHOMATIC CELLS
US20080090775A1 (en) * 2005-10-31 2008-04-17 Chong Huang Antagonist of TEB4 and Methods of Use
EP1948674A4 (en) * 2005-11-02 2009-02-04 Protiva Biotherapeutics Inc Modified sirna molecules and uses thereof
CA2626584A1 (en) * 2005-11-04 2007-05-18 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of nav1.8 gene
AU2006311730B2 (en) 2005-11-09 2010-12-02 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of Factor V Leiden mutant gene
US8067558B2 (en) 2005-12-19 2011-11-29 New York University Constitutively active fragments of eukaryotic heat shock RNA
US7919603B2 (en) * 2005-12-19 2011-04-05 New York University Heat shock RNA
EP1969143A4 (en) * 2005-12-20 2009-07-22 Isis Pharmaceuticals Inc DOUBLE-STRANDED NUCLEIC ACID MOLECULES TARGETING ALPHA IL-4 RECEPTOR
US8258287B2 (en) * 2005-12-21 2012-09-04 Centre de Cooperation Internationale en Recherche Agronomique pour le Developpment (CIRAD) Interfering RNAs targeting the morbillivirus nucleoprotein gene
MX2008008302A (en) * 2005-12-22 2009-01-21 Exegenics Inc Compositions and methods for regulating complement system.
AR057252A1 (en) * 2005-12-27 2007-11-21 Alcon Mfg Ltd INHIBITION OF RHO KINASE MEDIATED BY ARNI FOR THE TREATMENT OF EYE DISORDERS
US8673873B1 (en) 2005-12-28 2014-03-18 Alcon Research, Ltd. RNAi-mediated inhibition of phosphodiesterase type 4 for treatment of cAMP-related ocular disorders
TW200731980A (en) * 2005-12-29 2007-09-01 Alcon Mfg Ltd RNAi-mediated inhibition of HIF1A for treatment of ocular angiogenesis
US7444453B2 (en) * 2006-01-03 2008-10-28 International Business Machines Corporation Address translation device
JP5881270B2 (en) 2006-01-05 2016-03-09 チルドレンズ メディカル センター コーポレーション Regulatory factors of NFAT
NZ596322A (en) * 2006-01-17 2013-02-22 Synthon Biopharmaceuticals Bv Compositions and methods for humanization and optimization of N-glycans in duckweed plants
US20090060921A1 (en) * 2006-01-17 2009-03-05 Biolex Therapeutics, Inc. Glycan-optimized anti-cd20 antibodies
WO2007084954A2 (en) * 2006-01-19 2007-07-26 The Board Of Trustees Of The University Of Illinois Selective inhibition of ig20 splice variants to treat cancers
DOP2007000015A (en) 2006-01-20 2007-08-31 Quark Biotech Inc THERAPEUTIC USES OF RTP801 INHIBITORS
US7825099B2 (en) 2006-01-20 2010-11-02 Quark Pharmaceuticals, Inc. Treatment or prevention of oto-pathologies by inhibition of pro-apoptotic genes
PL2161038T3 (en) 2006-01-26 2014-06-30 Ionis Pharmaceuticals Inc Compositions and their uses directed to Huntingtin
US8229398B2 (en) * 2006-01-30 2012-07-24 Qualcomm Incorporated GSM authentication in a CDMA network
US20090221435A1 (en) * 2006-02-08 2009-09-03 Dharmacon, Inc. Microarray for detecting and quantifying microrna
CN101384721A (en) 2006-02-13 2009-03-11 孟山都技术有限公司 Selection and stabilization of dsRNA constructs
JP4961549B2 (en) * 2006-02-16 2012-06-27 国立大学法人愛媛大学 SiRNA specific for androgen receptor gene
US7910566B2 (en) 2006-03-09 2011-03-22 Quark Pharmaceuticals Inc. Prevention and treatment of acute renal failure and other kidney diseases by inhibition of p53 by siRNA
FI20060246A0 (en) 2006-03-16 2006-03-16 Jukka Westermarck A new growth stimulating protein and its use
US7846908B2 (en) * 2006-03-16 2010-12-07 Alnylam Pharmaceuticals, Inc. RNAi modulation of TGF-beta and therapeutic uses thereof
KR20080106554A (en) * 2006-03-24 2008-12-08 노파르티스 아게 DDRSNA compositions and methods for treating HPP infection
AU2007233109B2 (en) 2006-03-31 2010-10-14 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of Eg5 gene
EP2371957A1 (en) * 2006-04-12 2011-10-05 Isis Pharmaceuticals, Inc. Compositions and their uses directed to hepcidin
US8017592B2 (en) * 2006-04-13 2011-09-13 Alcon Research, Ltd. RNAi-mediated inhibition of histamine receptor H1-related conditions
TW200808360A (en) * 2006-04-13 2008-02-16 Alcon Mfg Ltd RNAi-mediated inhibition of spleen tyrosine kinase-related inflammatory conditions
WO2007123391A1 (en) * 2006-04-20 2007-11-01 Academisch Ziekenhuis Leiden Therapeutic intervention in a genetic disease in an individual by modifying expression of an aberrantly expressed gene.
JP4812874B2 (en) 2006-04-28 2011-11-09 アルナイラム ファーマシューティカルズ， インコーポレイテッド Composition and method for suppressing expression of JC virus gene
WO2007143317A2 (en) * 2006-05-05 2007-12-13 Isis Pharmaceuticals, Inc Compounds and methods for modulating expression of crp
US8158598B2 (en) * 2006-05-05 2012-04-17 Isis Pharmaceuticals, Inc. Compositions and their uses directed to PTPR alpha
EP2021507A4 (en) 2006-05-11 2009-10-28 Alnylam Pharmaceuticals Inc Compositions and methods for inhibiting expression of the pcsk9 gene
TWI322690B (en) * 2006-05-11 2010-04-01 Flysun Dev Co Ltd Short interference ribonucleic acids for treating allergic dieases
US8243715B2 (en) * 2006-05-15 2012-08-14 Oracle Israel Ltd. Delivering sip-based call services to circuit-switched terminals
WO2007133758A1 (en) * 2006-05-15 2007-11-22 Physical Pharmaceutica, Llc Composition and improved method for preparation of small particles
AU2012201409B2 (en) * 2006-05-19 2014-06-12 Arrowhead Research Corporation RNAi-Mediated inhibition of tumor necrosis factor alpha-related conditions
WO2007137237A2 (en) * 2006-05-19 2007-11-29 The Scripps Research Institute Treatment of protein misfolding
AU2007253803B2 (en) * 2006-05-19 2012-05-24 Alnylam Pharmaceuticals, Inc. RNAi modulation of Aha and therapeutic uses thereof
EP1857548A1 (en) * 2006-05-19 2007-11-21 Academisch Ziekenhuis Leiden Means and method for inducing exon-skipping
WO2007136758A2 (en) * 2006-05-19 2007-11-29 Board Of Regents, The University Of Texas System Sirna inhibition of p13k p85, p110, and akt2 and methods of use
CA2650416A1 (en) 2006-05-19 2007-11-29 Alcon Research, Ltd. Rnai-mediated inhibition of tumor necrosis factor .alpha.-related conditions
WO2007137220A2 (en) * 2006-05-22 2007-11-29 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of ikk-b gene
US9273356B2 (en) 2006-05-24 2016-03-01 Medtronic, Inc. Methods and kits for linking polymorphic sequences to expanded repeat mutations
US8598333B2 (en) * 2006-05-26 2013-12-03 Alnylam Pharmaceuticals, Inc. SiRNA silencing of genes expressed in cancer
WO2007143584A2 (en) * 2006-06-02 2007-12-13 Alcon Research, Ltd. RNAi-MEDIATED INHIBITION OF STROMAL CELL-DERIVED FACTOR 1-RELATED TARGETS FOR TREATMENT OF NEOVASCULARIZATION-RELATED CONDITIONS
KR20090031557A (en) * 2006-06-09 2009-03-26 가부시키가이샤 야쿠루트 혼샤 Genes related to immortalization of human cancer cells and uses thereof
US7915399B2 (en) * 2006-06-09 2011-03-29 Protiva Biotherapeutics, Inc. Modified siRNA molecules and uses thereof
EP2026843A4 (en) * 2006-06-09 2011-06-22 Quark Pharmaceuticals Inc Therapeutic uses of inhibitors of rtp801l
ES2390499T3 (en) * 2006-06-12 2012-11-13 Opko Pharmaceuticals, Llc Compositions and methods for inhibition of angiogenesis by sirna
KR100794705B1 (en) * 2006-06-13 2008-01-14 (주)바이오니아 Method to Inhibit Expression of Target mRNA Using SiRNA Considering Selective Splicing
GB0612342D0 (en) 2006-06-21 2006-08-02 Glaxosmithkline Biolog Sa Method
WO2008005769A2 (en) * 2006-06-30 2008-01-10 Immusol, Incorporated Methods of inhibiting hcv replication
WO2008008719A2 (en) * 2006-07-10 2008-01-17 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the myc gene
JP4756271B2 (en) * 2006-07-18 2011-08-24 独立行政法人産業技術総合研究所 Cancer cell aging, apoptosis inducer
EP1884569A1 (en) 2006-07-31 2008-02-06 Institut National De La Sante Et De La Recherche Medicale (Inserm) Sensitization of cancer cells to therapy using siNA targeting genes from the 1p and 19q chromosomal regions
US8138160B2 (en) 2006-08-03 2012-03-20 Warsaw Orthopedic, Inc. Reagents, methods and systems to suppress pro-inflammatory cytokines
AU2007281082A1 (en) * 2006-08-04 2008-02-07 Isis Pharmaceuticals, Inc. Compositions and methods for the modulation of JNK proteins
US8003620B2 (en) * 2006-08-04 2011-08-23 Isis Pharmaceuticals, Inc. Compositions and their uses directed to diacylglycerol acyltransferase 1
ES2911034T3 (en) 2006-08-08 2022-05-17 Univ Bonn Rheinische Friedrich Wilhelms Structure and use of 5' phosphate oligonucleotides
US20080039415A1 (en) * 2006-08-11 2008-02-14 Gregory Robert Stewart Retrograde transport of sirna and therapeutic uses to treat neurologic disorders
JP6047270B2 (en) * 2006-08-11 2016-12-21 バイオマリン テクノロジーズ ベー．フェー． Methods and means for treating genetic disorders associated with instability of DNA repeats
JPWO2008029790A1 (en) * 2006-09-04 2010-01-21 協和発酵キリン株式会社 New nucleic acid
US7872118B2 (en) * 2006-09-08 2011-01-18 Opko Ophthalmics, Llc siRNA and methods of manufacture
CA2663803A1 (en) 2006-09-18 2008-03-27 Alnylam Pharmaceuticals, Inc. Rnai modulation of scap and therapeutic uses thereof
EP2083272B1 (en) * 2006-09-19 2014-09-17 Accural INC. Cancer cell identification marker and cancer cell proliferation inhibitor
AU2007299629C1 (en) 2006-09-21 2012-05-10 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the HAMP gene
AR055648A1 (en) * 2006-09-21 2007-08-29 Gen Med Sa A DOUBLE-CHAIN RNA OLIGONUCLEOTIDE A PHARMACEUTICAL OR COSMETIC COMPOSITION THAT UNDERSTANDS AND USES IT IN THE PREPARATION OF A MEDICINAL PRODUCT FOR THE TREATMENT OF DISEASES RELATED TO ANDROGEN METABOLISM
WO2008036841A2 (en) 2006-09-22 2008-03-27 Dharmacon, Inc. Tripartite oligonucleotide complexes and methods for gene silencing by rna interference
JP5876637B2 (en) * 2006-10-18 2016-03-02 マリーナ バイオテック，インコーポレイテッド Nicked or gapped nucleic acid molecules and their use
WO2008063760A2 (en) * 2006-10-18 2008-05-29 The University Of Texas M.D. Anderson Cancer Center Methods for treating cancer targeting transglutaminase
JP2010507387A (en) * 2006-10-25 2010-03-11 クアーク・ファーマスーティカルス、インコーポレイテッド Novel siRNA and method of using the same
US8324367B2 (en) 2006-11-03 2012-12-04 Medtronic, Inc. Compositions and methods for making therapies delivered by viral vectors reversible for safety and allele-specificity
US9375440B2 (en) * 2006-11-03 2016-06-28 Medtronic, Inc. Compositions and methods for making therapies delivered by viral vectors reversible for safety and allele-specificity
WO2008060478A2 (en) * 2006-11-09 2008-05-22 The Board Of Regents Of The University Of Texas System Hedgehog signaling pathway proteins and uses thereof
US20100068198A1 (en) * 2006-11-09 2010-03-18 Unibioscreen S.A. Targeting of alpha-1 or alpha-3 subunit of na+, k+-atpase in the treatment of proliferative diseases
CA2669520C (en) * 2006-11-13 2016-07-26 The Medical Research, Infrastructure, And Health Services Fund Of The Tel Aviv Medical Center Methods of treating cancer using sirna molecules directed against cd24
US7819842B2 (en) 2006-11-21 2010-10-26 Medtronic, Inc. Chronically implantable guide tube for repeated intermittent delivery of materials or fluids to targeted tissue sites
US8034921B2 (en) * 2006-11-21 2011-10-11 Alnylam Pharmaceuticals, Inc. IRNA agents targeting CCR5 expressing cells and uses thereof
US7988668B2 (en) * 2006-11-21 2011-08-02 Medtronic, Inc. Microsyringe for pre-packaged delivery of pharmaceuticals
MX2009005527A (en) * 2006-11-27 2009-06-08 Isis Pharmaceuticals Inc Methods for treating hypercholesterolemia.
US8093222B2 (en) 2006-11-27 2012-01-10 Isis Pharmaceuticals, Inc. Methods for treating hypercholesterolemia
US20080171719A1 (en) * 2006-11-28 2008-07-17 Alcon Manufacturing, Ltd. RNAi-MEDIATED INHIBITION OF AQUAPORIN 1 FOR TREATMENT OF IOP-RELATED CONDITIONS
JPWO2008084319A1 (en) * 2006-12-18 2010-04-30 協和発酵キリン株式会社 New nucleic acid
JP2010512765A (en) * 2006-12-22 2010-04-30 エフ．ホフマン−ラ ロシュ アーゲー Selection method
US8476243B2 (en) 2006-12-29 2013-07-02 Transderm, Inc. Methods and compositions for treating keratin hyperproliferative disorders
US7754698B2 (en) * 2007-01-09 2010-07-13 Isis Pharmaceuticals, Inc. Modulation of FR-alpha expression
CA2712056C (en) 2007-01-16 2016-06-21 The University Of Queensland Method of inducing an immune response
JP2010516625A (en) 2007-01-24 2010-05-20 インサート セラピューティクス， インコーポレイテッド Polymer-drug conjugates with tether groups for controlled drug delivery
US20100183696A1 (en) 2007-01-30 2010-07-22 Allergan, Inc Treating Ocular Diseases Using Peroxisome Proliferator-Activated Receptor Delta Antagonists
TW200900420A (en) 2007-02-02 2009-01-01 Amgen Inc Hepcidin, hepcidin antagonists and methods of use
US20080188433A1 (en) * 2007-02-07 2008-08-07 Academia Sinica Methods of diagnosis of spinal muscular atrophy and treatments thereof
US20090163431A1 (en) * 2007-02-14 2009-06-25 Ontherex Llc Compositions and methods for modulation of pdx-1
US7872119B2 (en) * 2007-02-26 2011-01-18 Quark Pharmaceuticals, Inc. Inhibitors of RTP801 and their use in disease treatment
WO2008104978A2 (en) * 2007-02-28 2008-09-04 Quark Pharmaceuticals, Inc. Novel sirna structures
WO2008109357A1 (en) * 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting apob gene expression and uses thereof
WO2008109381A2 (en) * 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting hif1a gene expression and uses thereof
JP2010519906A (en) * 2007-03-02 2010-06-10 エムディーアールエヌエー，インコーポレイテッド NUCLEIC ACID COMPOUND AND USE THEREOF FOR SUPPRESSING EXPRESSION OF ERBB FAMILY GENE
US20100055784A1 (en) * 2007-03-02 2010-03-04 Mdrna, Inc. Nucleic acid compounds for inhibiting wnt gene expression and uses thereof
TWI419902B (en) * 2007-03-02 2013-12-21 百靈佳殷格翰製藥公司 Improvement of protein production
EP2126082A1 (en) * 2007-03-02 2009-12-02 MDRNA, Inc. Nucleic acid compounds for inhibiting bcl2 gene expression and uses thereof
EP2126080A2 (en) * 2007-03-02 2009-12-02 MDRNA, Inc. Nucleic acid compounds for inhibiting akt gene expression and uses thereof
WO2008109373A1 (en) * 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting erbb gene expression and uses thereof
US20100105134A1 (en) * 2007-03-02 2010-04-29 Mdrna, Inc. Nucleic acid compounds for inhibiting gene expression and uses thereof
CA2679867A1 (en) * 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting vegf family gene expression and uses thereof
US20090018099A1 (en) * 2007-03-02 2009-01-15 Hitto Kaufmann Protein production
WO2009029293A2 (en) * 2007-03-02 2009-03-05 Mdrna, Inc. Nucleic acid compounds for inhibiting myc gene expression and uses thereof
WO2008109362A1 (en) * 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting vegf gene expression and uses thereof
EP2121925A2 (en) * 2007-03-02 2009-11-25 MDRNA, Inc. Nucleic acid compounds for inhibiting ras gene expression and uses thereof
CA2680058C (en) * 2007-03-08 2019-04-16 University Health Network Induction of apoptosis and inhibition of cell proliferation through modulation of carnitine palmitoyltransferase 1c activity
JP5832721B2 (en) * 2007-03-14 2015-12-16 バイオンシル・エス．アール．エル．Ｂｉｏｎｓｉｌ Ｓ．Ｒ．Ｌ． Modulator compounds with drug resistance in epithelial tumor cells
JP5103621B2 (en) * 2007-03-20 2012-12-19 国立大学法人愛媛大学 SiRNA specific for the ADAT1 gene
US7812002B2 (en) * 2007-03-21 2010-10-12 Quark Pharmaceuticals, Inc. Oligoribonucleotide inhibitors of NRF2 and methods of use thereof for treatment of cancer
RU2559536C2 (en) 2007-03-24 2015-08-10 Джензим Корпорейшн Introduction of antisense oliginucleotides, complementary to human apolypoprotein b
PE20090064A1 (en) * 2007-03-26 2009-03-02 Novartis Ag DOUBLE-CHAIN RIBONUCLEIC ACID TO INHIBIT THE EXPRESSION OF THE HUMAN E6AP GENE AND THE PHARMACEUTICAL COMPOSITION THAT INCLUDES IT
AP3018A (en) 2007-03-29 2014-10-31 Alnylam Pharmaceuticals Inc Compositions and methods for inhibiting expressionof a gene from the ebola
GB0707069D0 (en) * 2007-04-12 2007-05-23 Medical Res Council Methods and uses
WO2008124927A1 (en) * 2007-04-13 2008-10-23 Vincent Research & Consulting Inc. Sirna against thymidylate synthase and uses thereof in cancer treatment regimens
CN101842483A (en) * 2007-05-01 2010-09-22 桑塔里斯制药公司 Rna antagonist compounds for the modulation of beta-catenin
WO2008143774A2 (en) * 2007-05-01 2008-11-27 University Of Massachusetts Methods and compositions for locating snp heterozygosity for allele specific diagnosis and therapy
JP5346923B2 (en) * 2007-05-04 2013-11-20 インデックス・ファーマシューティカルズ・アクチエボラーグ Tumor growth inhibitory compounds and methods of use thereof
AU2008251037A1 (en) * 2007-05-15 2008-11-20 Johnson & Johnson Research Pty Limited Suppression of viruses involved in respiratory infection or disease
US9353368B2 (en) 2007-05-23 2016-05-31 Ge Healthcare Dharmacon, Inc. Micro-RNA scaffolds and non-naturally occurring micro-RNAs
US9365634B2 (en) 2007-05-29 2016-06-14 Angiochem Inc. Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues
CN101314775B (en) * 2007-05-31 2013-02-06 厦门大学 RNA interference targets for AIDS treatment
EP2152897B1 (en) * 2007-06-05 2015-02-18 Melica HB Methods and materials related to hair pigmentation and cancer
US20100273854A1 (en) * 2007-06-15 2010-10-28 Hagar Kalinski Compositions and methods for inhibiting nadph oxidase expression
US20090054366A1 (en) * 2007-06-15 2009-02-26 Reliance Life Sciences Pvt. Ltd. RNAi MEDIATED KNOCKDOWN OF NUMA FOR CANCER THERAPY
AU2012203759B2 (en) * 2007-06-15 2012-12-13 Arrowhead Pharmaceuticals, Inc. RNAi inhibition of alpha-ENaC expression
AR066984A1 (en) * 2007-06-15 2009-09-23 Novartis Ag INHIBITION OF THE EXPRESSION OF THE ALFA SUBUNITY OF THE SODIUM EPITELIAL CHANNEL (ENAC) THROUGH ARNI (INTERFERENCE RNA)
WO2009001359A2 (en) 2007-06-27 2008-12-31 Quark Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of pro-apoptotic genes
WO2009002193A1 (en) * 2007-06-27 2008-12-31 Auckland Uniservices Limited Polypeptides and polynucleotides for artemin and related ligands, and methods of use thereof
AU2008272051A1 (en) 2007-07-03 2009-01-08 Cytopathfinder, Inc. Treatment of influenza
EP2316943B1 (en) 2007-07-05 2013-06-19 Novartis AG DSRNA for treating viral infection
AU2008273094B2 (en) * 2007-07-12 2013-05-09 Prosensa Technologies B.V. Molecules for targeting compounds to various selected organs, tissues or tumor cells
CA2942716C (en) * 2007-07-12 2019-07-09 Biomarin Technologies B.V. Molecules for targeting compounds to various selected organs or tissues
EP2017340A1 (en) * 2007-07-16 2009-01-21 Qiagen GmbH Positive controls for expression modulating experiments
TW200914052A (en) * 2007-08-03 2009-04-01 Alcon Res Ltd RNAi-related inhibition of TNFα signaling pathway for treatment of glaucoma
CL2008002277A1 (en) 2007-08-03 2009-07-17 Alcon Res Ltd Method for treating a tnf alpha-related eye disorder comprising an interfering RNA molecule that acts on the expression of tnfr1 or tace mRNA by RNA interference; interfering RNA molecule; composition comprising said interferer.
US8435510B2 (en) * 2007-08-08 2013-05-07 Sutter West Bay Hospitals Platelet derived growth factor receptor supports cytomegalovirus infectivity
CN101821410B (en) * 2007-08-10 2016-01-27 温德维亚集团公司 Gene Silencing by Brothers of Imprinted Locus Regulators (BORIS)
CA2697055A1 (en) * 2007-08-21 2009-02-26 Scott And White Memorial Hospital And Scott, Sherwood And Brindley Found Ation Methods and compositions for post-transcriptional gene silencing
RU2010111135A (en) * 2007-08-24 2011-10-27 Онкотерапи Сайенс, Инк. (Jp) CDCA5 GENES RELATED TO MALIGNANT TUMORS EPHA7. STK31 and WDHD1
DK2193140T3 (en) * 2007-08-27 2017-01-23 Iglobe Health Inst Llc COMPOSITIONS OF ASYMMETRIC INTERFERRING RNA AND ITS APPLICATIONS
CL2008002775A1 (en) 2007-09-17 2008-11-07 Amgen Inc Use of a sclerostin binding agent to inhibit bone resorption.
CA2704737A1 (en) * 2007-09-18 2009-09-03 Intradigm Corporation Compositions comprising k-ras sirna and methods of use
DK2195428T3 (en) * 2007-09-19 2014-03-03 Applied Biosystems Llc SIRNA SEQUENCE-INDEPENDENT MODIFICATION FORMS TO REDUCE TARGET-FAILING PHENOTYPIC EFFECTS OF RNAI, AND STABILIZED FORMS THEREOF
KR101660989B1 (en) * 2007-10-01 2016-09-28 아이오니스 파마수티컬즈, 인코포레이티드 Antisense modulation of fibroblast growth factor receptor 4 expression
RU2487716C2 (en) * 2007-10-03 2013-07-20 Кварк Фармасьютикалс, Инк. New structures of small interfering rna (sirna)
US9540649B2 (en) * 2007-10-12 2017-01-10 The Provost, Fellows And Scholars Of The College Of The Holy And Undivided Trinity Of Queen Elizabeth Near Dublin Method for opening tight junctions
USRE48468E1 (en) 2007-10-26 2021-03-16 Biomarin Technologies B.V. Means and methods for counteracting muscle disorders
CN101896186A (en) * 2007-10-26 2010-11-24 莱顿教学医院 Means and methods for combating muscle disorders
JP2011517279A (en) * 2007-10-29 2011-06-02 ユニバーシティ オブ マサチューセッツ Yeast cell wall particles (YCWP) multi-layered nanoparticles for nucleic acid (siRNA) delivery
US8097712B2 (en) 2007-11-07 2012-01-17 Beelogics Inc. Compositions for conferring tolerance to viral disease in social insects, and the use thereof
WO2009061851A2 (en) 2007-11-09 2009-05-14 Isis Pharmaceuticals, Inc. Modulation of factor 7 expression
WO2009061852A2 (en) * 2007-11-09 2009-05-14 Isis Pharmaceuticals, Inc. Modulation of factor 9 expression
CA2707042A1 (en) 2007-12-10 2009-06-18 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of factor vii gene
US20100204305A1 (en) * 2007-12-11 2010-08-12 Lorus Therapeutics Inc. Small interfering rna molecules against ribonucleotide reductase and uses thereof
WO2009074990A2 (en) * 2007-12-12 2009-06-18 Quark Pharmaceuticals, Inc. Rtp801l sirna compounds and methods of use thereof
US8614311B2 (en) 2007-12-12 2013-12-24 Quark Pharmaceuticals, Inc. RTP801L siRNA compounds and methods of use thereof
NZ585784A (en) 2007-12-13 2012-09-28 Alnylam Pharmaceuticals Inc siRNAs for the treatment and prevention of respiratory syncytial virus (RSV) infection
BRPI0819688A2 (en) 2007-12-14 2015-06-16 Amgen Inc Process for treating bone fracture with anti-sclerostin antibodies.
WO2009079399A2 (en) * 2007-12-14 2009-06-25 Alnylam Pharmaceuticals, Inc. Method of treating neurodegenerative disease
KR100949791B1 (en) * 2007-12-18 2010-03-30 이동기 Novel siRNA structure and its use to minimize off-target effect and not saturate the RAN mechanism
US20110039785A1 (en) * 2007-12-20 2011-02-17 Angiochem Inc. Polypeptide-nucleic acid conjugates and uses thereof
EP2077335A1 (en) * 2007-12-22 2009-07-08 Universitätsklinikum Schleswig-Holstein EXO1 promoter polymorphism associated with exceptional life expectancy in humans
KR100942807B1 (en) * 2007-12-26 2010-02-18 재단법인서울대학교산학협력재단 Gene therapy and pharmaceutical composition for the prevention or treatment of lung cancer
AU2008342535B2 (en) * 2007-12-27 2015-02-05 Arbutus Biopharma Corporation Silencing of polo-like kinase expression using interfering RNA
EP2075333A1 (en) * 2007-12-28 2009-07-01 Qiagen GmbH Positive controls for expression modulating experiments
EP2242854A4 (en) * 2008-01-15 2012-08-15 Quark Pharmaceuticals Inc Sirna compounds and methods of use thereof
US20100297750A1 (en) * 2008-01-24 2010-11-25 Toru Natsume Polynucleotide or analogue thereof, and gene expression regulation method using the polynucleotide or the analogue thereof
US20110201668A1 (en) * 2008-01-30 2011-08-18 Korea Institute Of Science And Technology Regulation of neurotransmitter release through anion channels
EP2245039A4 (en) * 2008-01-31 2012-06-06 Alnylam Pharmaceuticals Inc Optimized methods for delivery of dsrna targeting the pcsk9 gene
AU2009210872A1 (en) * 2008-02-08 2009-08-13 Prosensa Holding Bv Methods and means for treating DNA repeat instability associated genetic disorders
CN102016036B (en) 2008-02-11 2015-04-08 阿克赛医药公司 Modified RNAi polynucleotides and uses thereof
US8188060B2 (en) 2008-02-11 2012-05-29 Dharmacon, Inc. Duplex oligonucleotides with enhanced functionality in gene regulation
WO2009137128A2 (en) * 2008-02-12 2009-11-12 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of cd45 gene
WO2009103067A2 (en) * 2008-02-14 2009-08-20 The Children's Hospital Of Philadelphia Compositions and methods to treat asthma
KR100870314B1 (en) * 2008-02-19 2008-11-25 고려대학교 산학협력단 Pharmaceutical composition containing nucleic acid for treating cancer
US20110097338A1 (en) * 2008-02-20 2011-04-28 Technische Universitaet Dresden Use of Substances for Sensitization of Tumor Cells to Radiation and/or Chemotherapy
KR101397407B1 (en) * 2008-03-05 2014-06-19 알닐람 파마슈티칼스 인코포레이티드 Compositions and methods for inhibiting expression of Eg5 and VEGF genes
KR101123130B1 (en) * 2008-03-17 2012-03-30 연세대학교 산학협력단 Inhibitors of cell migration, invasion, or angiogenesis by blocking the function of PTK7 protein
MX2010010303A (en) * 2008-03-20 2010-10-20 Quark Pharmaceuticals Inc NOVEL siRNA COMPOUNDS FOR INHIBITING RTP801.
EP2105145A1 (en) * 2008-03-27 2009-09-30 ETH Zürich Method for muscle-specific delivery lipid-conjugated oligonucleotides
WO2009123185A1 (en) * 2008-03-31 2009-10-08 独立行政法人産業技術総合研究所 Double-stranded lipid-modified rna having high rna interference effect
US20110097335A1 (en) * 2008-03-31 2011-04-28 Yoshikazu Sugimoto Abc transporter protein expression inhibitor
US7956044B1 (en) 2008-04-03 2011-06-07 The Board Of Regents Of The University Of Oklahoma Compositions comprising inhibitors of RNA binding proteins and methods of producing and using same
TWI348916B (en) * 2008-04-03 2011-09-21 Univ Nat Taiwan A novel treatment tool for cancer: rna interference of bcas2
US8198255B2 (en) * 2008-05-16 2012-06-12 The Board Of Regents Of The University Of Oklahoma SiRNA-mediated inhibition of doublecortin and Ca2+/calmodulin-dependent kinase-like-1
US7902166B2 (en) * 2008-04-03 2011-03-08 The Board Of Regents Of The University Of Oklahoma Compositions comprising inhibitors of RNA binding proteins and methods of producing and using same
US8936941B2 (en) 2008-04-03 2015-01-20 The Board Of Regents Of The University Of Oklahoma Compositions useful for cancer detection and treatment, a cancer stem cell model, and methods of production and use thereof
JP2011516065A (en) * 2008-04-04 2011-05-26 カランド ファーマシューティカルズ， インコーポレイテッド Compositions and uses of EPAS1 inhibitors
CA2720887A1 (en) * 2008-04-09 2009-10-15 Inserm (Institut National De La Sante Et De La Recherche Medicale) Inhibitors of stim1 for the treatment of cardiovascular disorders
WO2009129319A2 (en) * 2008-04-15 2009-10-22 Protiva Biotherapeutics, Inc. Silencing of csn5 gene expression using interfering rna
WO2009144704A2 (en) * 2008-04-15 2009-12-03 Quark Pharmaceuticals, Inc. siRNA COMPOUNDS FOR INHIBITING NRF2
WO2009129465A2 (en) 2008-04-17 2009-10-22 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of xbp-1 gene
USRE48948E1 (en) 2008-04-18 2022-03-01 Warsaw Orthopedic, Inc. Clonidine compounds in a biodegradable polymer
PT2279008T (en) * 2008-04-18 2019-05-20 Angiochem Inc Pharmaceutical compositions of paclitaxel, paclitaxel analogs or paclitaxel conjugates and related methods of preparation and use
EP2276455A2 (en) 2008-04-22 2011-01-26 Centre National de la Recherche Scientifique Use of k1f13a and ap-1 inhibitors for inhibiting melanogenesis
US8324366B2 (en) 2008-04-29 2012-12-04 Alnylam Pharmaceuticals, Inc. Compositions and methods for delivering RNAI using lipoproteins
EP2119783A1 (en) 2008-05-14 2009-11-18 Prosensa Technologies B.V. Method for efficient exon (44) skipping in Duchenne Muscular Dystrophy and associated means
US9663585B2 (en) 2008-05-16 2017-05-30 The Board Of Regents Of The University Of Oklahoma Anti-DCLK1 monoclonal antibodies and methods of production and use thereof
EP2291544B1 (en) * 2008-05-16 2017-10-25 The Children's Hospital of Philadelphia Genetic alterations on chromosomes 21q, 6q and 15q and methods of use thereof for the diagnosis and treatment of type i diabetes
WO2009141146A1 (en) 2008-05-21 2009-11-26 Gunther Hartmann 5' triphosphate oligonucleotide with blunt end and uses thereof
WO2009143391A2 (en) * 2008-05-22 2009-11-26 Isis Pharmaceuticals, Inc Methods for modulation expression of creb
WO2009143390A2 (en) 2008-05-22 2009-11-26 Isis Pharmaceuticals, Inc. Methods for modulating expression of rbp4
US20110130442A1 (en) * 2008-06-04 2011-06-02 Kyowa Hakko Kirin Co., Ltd. Nucleic acid capable of controlling degranulation of mast cell
US20110092575A1 (en) * 2008-06-06 2011-04-21 Assignment for Published Patent Application Gene Techno Science Co., Ltd. Sirna of human osteopontin
US8431692B2 (en) * 2008-06-06 2013-04-30 Quark Pharmaceuticals, Inc. Compositions and methods for treatment of ear disorders
EP2297311A1 (en) * 2008-06-06 2011-03-23 Medizinische Universität Graz Compounds reducing or inhibiting the expression of pkd1 for diagnosis and therapy of brain tumors
US20090312194A1 (en) * 2008-06-13 2009-12-17 Oregon Health & Science University Selection of personalized cancer therapy regimens using interfering rna functional screening
EP2235177B1 (en) * 2008-06-13 2012-07-18 RiboxX GmbH Method for enzymatic synthesis of chemically modified rna
TWI455944B (en) * 2008-07-01 2014-10-11 Daiichi Sankyo Co Ltd Double-stranded polynucleotides
US20110172293A1 (en) * 2008-07-08 2011-07-14 Fish Jason E Methods and Compositions for Modulating Angiogenesis
EP2310021A4 (en) * 2008-07-10 2012-06-27 Merck Sharp & Dohme METHODS OF USING COMPOSITIONS COMPRISING MIR-192 AND / OR MIR-215 FOR THE TREATMENT OF CANCER
HRP20160261T1 (en) 2008-07-10 2016-06-03 Regenesance B.V. COMPLEMENTARY ANTAGONISTS AND THEIR USE
US20110184046A1 (en) * 2008-07-11 2011-07-28 Dinah Wen-Yee Sah Compositions And Methods For Inhibiting Expression Of GSK-3 Genes
WO2010004051A1 (en) * 2008-07-11 2010-01-14 Medizinische Universität Innsbruck Antagonists of nr2f6 for augmenting the immune response
WO2010008562A2 (en) * 2008-07-16 2010-01-21 Recombinetics Methods and materials for producing transgenic animals
WO2010008582A2 (en) 2008-07-18 2010-01-21 Rxi Pharmaceuticals Corporation Phagocytic cell drug delivery system
WO2010008069A1 (en) * 2008-07-18 2010-01-21 国立大学法人名古屋大学 Cell proliferation inhibitor
CN101632833B (en) * 2008-07-25 2013-11-06 上海市计划生育科学研究所 Prostatic cancer related gene and application thereof
JP2011529686A (en) * 2008-07-29 2011-12-15 ザ ボード オブ リージェンツ オブ ザ ユニバーシティー オブ テキサス システム Selective inhibition of polyglutamine protein expression
US20110237646A1 (en) * 2008-08-07 2011-09-29 Isis Pharmaceuticals, Inc. Modulation of transthyretin expression for the treatment of cns related disorders
US8669102B2 (en) 2008-08-14 2014-03-11 Isis Pharmaceuticals, Inc. Modulation of prion expression
DK2331141T3 (en) 2008-08-25 2016-04-04 Excaliard Pharmaceuticals Inc Antisense oligonucleotides WHO IS TARGETING connective tissue, AND USES THEREOF
US8946172B2 (en) * 2008-08-25 2015-02-03 Excaliard Pharmaceuticals, Inc. Method for reducing scarring during wound healing using antisense compounds directed to CTGF
US20130324478A1 (en) * 2008-09-08 2013-12-05 Laurence Faure Pharmacodiagnosis Test Targeting Oncology and Neurodegeneration
ES2799507T3 (en) 2008-09-10 2020-12-18 Univ Rutgers Imaging of individual mRNA molecules using multiple probes labeled with a single marker
CA2737180C (en) 2008-09-15 2019-02-19 Children's Medical Center Corporation Modulation of bcl11a for treatment of hemoglobinopathies
JP2010068723A (en) * 2008-09-16 2010-04-02 Tokyo Medical & Dental Univ Nucleic acid medicine for treating allergic disease
AU2009293658A1 (en) * 2008-09-22 2010-03-25 James Cardia Reduced size self-delivering RNAi compounds
WO2010036962A1 (en) 2008-09-25 2010-04-01 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of serum amyloid a gene
WO2010042547A1 (en) 2008-10-06 2010-04-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of an rna from west nile virus
CA2739788A1 (en) * 2008-10-07 2010-04-15 President And Fellows Of Harvard College Telomerase inhibitors that bind to the cr4-cr5 domain of the rna component of human telomerase and methods of use thereof
WO2010043049A1 (en) 2008-10-15 2010-04-22 Angiochem Inc. Etoposide and doxorubicin conjugates for drug delivery
CN109797150A (en) 2008-10-15 2019-05-24 Ionis制药公司 The adjusting of factor 11 expression
BRPI0920209A2 (en) 2008-10-15 2015-12-22 Angiochem Inc conjugates of glp-1 agonists and their uses
AU2009303355B2 (en) * 2008-10-15 2015-10-01 Promising Future, Llc FAS/FASL or other death receptor targeted methods and compositions for killing tumor cells
AU2015249072C1 (en) * 2008-10-20 2022-10-27 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of transthyretin
SG10201809460SA (en) * 2008-10-20 2018-11-29 Alnylam Pharmaceuticals Inc Compositions and methods for inhibiting expression of transthyretin
WO2010048590A1 (en) * 2008-10-23 2010-04-29 Alnylam Pharmaceuticals, Inc. Methods and compositions for prevention or treatment of rsv infection using modified duplex rna molecules
SI3133160T1 (en) 2008-10-24 2019-05-31 Sarepta Therapeutics, Inc. Exon skipping compositions for dmd
WO2010059400A1 (en) * 2008-10-30 2010-05-27 The Translational Genomics Research Institute Methods and kits to identify invasive glioblastoma
US9095592B2 (en) * 2008-11-07 2015-08-04 The Research Foundation For The State University Of New York Bruton's tyrosine kinase as anti-cancer drug target
US20100267803A1 (en) * 2008-11-07 2010-10-21 The Research Foundation Of State University Of New York Regulators Of Fat Metabolism As Anti-Cancer Targets
CA2742771A1 (en) * 2008-11-13 2010-05-20 Modgene, Llc Modification of amyloid-beta load in non-brain tissue
WO2010059226A2 (en) * 2008-11-19 2010-05-27 Rxi Pharmaceuticals Corporation Inhibition of map4k4 through rnai
JP2012509331A (en) 2008-11-21 2012-04-19 アイシス ファーマシューティカルズ， インコーポレーテッド Combination therapy for the treatment of cancer
RU2015151857A (en) 2008-12-02 2019-01-15 Уэйв Лайф Сайенсес Джапан, Инк. METHOD FOR SYNTHESIS OF NUCLEIC ACIDS MODIFIED BY PHOSPHOR ATOMIC
WO2010064851A2 (en) * 2008-12-02 2010-06-10 울산대학교 산학협력단 Mtor-targeted sirna having an interspecific cross reaction, recombination vector containing same, and pharmaceutical composition containing same
MX358603B (en) * 2008-12-04 2018-08-28 Curna Inc Treatment of tumor suppressor gene related diseases by inhibition of natural antisense transcript to the gene.
NZ593743A (en) 2008-12-04 2012-07-27 Opko Ophthalmics Llc Compositions and methods for selective inhibition of pro-angiogenic vegf isoforms
ES2760912T3 (en) * 2008-12-04 2020-05-18 Curna Inc Treatment of diseases related to Sirtuin 1 (SIRT1) by inhibition of the natural antisense transcript of Sirtuin 1
US9914754B2 (en) 2008-12-05 2018-03-13 Angiochem Inc. Conjugates of neurotensin or neurotensin analogs and uses thereof
WO2010068816A1 (en) 2008-12-10 2010-06-17 Alnylam Pharmaceuticals, Inc. Gnaq targeted dsrna compositions and methods for inhibiting expression
MX2011006577A (en) * 2008-12-17 2011-07-12 Ganisation Commonwealth Scient And Ind Res Or Methods of modulating the sex of avians.
US20100249214A1 (en) * 2009-02-11 2010-09-30 Dicerna Pharmaceuticals Multiplex dicer substrate rna interference molecules having joining sequences
US20110256090A1 (en) * 2008-12-18 2011-10-20 Universite De Montpellier 2 Sciences Et Techniques Method for Identifying Genes Involved in Trail-Induced Apoptosis and Therapeutic Applications Thereof
US11408003B2 (en) 2008-12-18 2022-08-09 Dicerna Pharmaceuticals, Inc. Extended dicer substrate agents and methods for the specific inhibition of gene expression
CA2747013C (en) * 2008-12-18 2022-05-31 Dicerna Pharmaceuticals, Inc. Extended dicer substrate agents and methods for the specific inhibition of gene expression
WO2010078536A1 (en) * 2009-01-05 2010-07-08 Rxi Pharmaceuticals Corporation Inhibition of pcsk9 through rnai
JPWO2010079819A1 (en) * 2009-01-08 2012-06-28 塩野義製薬株式会社 Pharmaceutical composition for the treatment of obesity or diabetes
WO2010083162A2 (en) * 2009-01-13 2010-07-22 The Board Of Regents Of The University Of Texas System Unc-45a splice variants based cancer diagnostics and therapeutics
WO2010093263A1 (en) * 2009-02-03 2010-08-19 Solilrna Biosciences Limited Compositions and methods for the treatment and prevention of neoplastic disorders
WO2010089221A1 (en) * 2009-02-03 2010-08-12 F. Hoffmann-La Roche Ag Compositions and methods for inhibiting expression of ptp1b genes
WO2010090762A1 (en) 2009-02-04 2010-08-12 Rxi Pharmaceuticals Corporation Rna duplexes with single stranded phosphorothioate nucleotide regions for additional functionality
WO2010091396A2 (en) * 2009-02-09 2010-08-12 Archemix Corp. Aptamers to von willerbrand factor and their use as thrombotic, hematologic and cardiovascular disease therapeutics
WO2010093904A2 (en) * 2009-02-12 2010-08-19 Curna, Inc. Treatment of brain derived neurotrophic factor (bdnf) related diseases by inhibition of natural antisense transcript to bdnf
WO2010091878A2 (en) * 2009-02-13 2010-08-19 Silence Therapeutics Ag Means for inhibiting the expression of opa1
CN102333869A (en) * 2009-02-24 2012-01-25 里博克斯艾克斯有限公司 Improved design of small-interfering rna
GB2468477A (en) * 2009-03-02 2010-09-15 Mina Therapeutics Ltd Double stranded RNA molecule comprising siRNA and miRNA precursors
US20110319317A1 (en) * 2009-03-04 2011-12-29 Opko Curna, Llc Treatment of sirtuin 1 (sirt1) related diseases by inhibition of natural antisense transcript to sirt1
JPWO2010101249A1 (en) 2009-03-06 2012-09-10 国立大学法人三重大学 Method for enhancing T cell function
JP6032724B2 (en) * 2009-03-12 2016-11-30 アルナイラム ファーマシューティカルズ， インコーポレイテッドＡｌｎｙｌａｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． Lipid preparation composition and method for inhibiting expression of Eg5 gene and VEGF gene
WO2010107733A2 (en) * 2009-03-16 2010-09-23 Curna, Inc. Treatment of nuclear factor (erythroid-derived 2)-like 2 (nrf2) related diseases by inhibition of natural antisense transcript to nrf2
US9107933B2 (en) 2009-03-16 2015-08-18 Isis Pharmaceuticals, Inc. Compositions and methods of targeting apolipoprotein B for the reduction of apolipoprotein C-III
EA201171144A1 (en) * 2009-03-19 2012-04-30 Мерк Шарп Энд Домэ Корп. MEDIATED RNA-INTERFERENCE INHIBITING THE EXPRESSION OF THE HOMEPHOLOGICAL GENE 1 BTB AND CNC, THE MAIN TRANSFCRIPTION FACTOR WITH LEUKIN LIGHTNING 1 (Bach1) USING SMALL INTERFACE
EP2408458A1 (en) * 2009-03-19 2012-01-25 Merck Sharp&Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 6 (STAT6) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20100239632A1 (en) 2009-03-23 2010-09-23 Warsaw Orthopedic, Inc. Drug depots for treatment of pain and inflammation in sinus and nasal cavities or cardiac tissue
CN102378766A (en) 2009-03-23 2012-03-14 夸克医药公司 Compound compositions and methods for treating cancer and fibrotic diseases
US20120004281A1 (en) * 2009-03-27 2012-01-05 Merck Sharp & Dohme Corp RNA Interference Mediated Inhibition of the Nerve Growth Factor Beta Chain (NGFB) Gene Expression Using Short Interfering Nucleic Acid (siNA)
WO2010111464A1 (en) * 2009-03-27 2010-09-30 Merck Sharp & Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF APOPTOSIS SIGNAL-REGULATING KINASE 1 (ASK1) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20120022143A1 (en) * 2009-03-27 2012-01-26 Merck Sharp & Dohme Corp RNA Interference Mediated Inhibition of the Thymic Stromal Lymphopoietin (TSLP) Gene Expression Using Short Interfering Nucliec Acid (siNA)
US20120088814A1 (en) 2009-03-31 2012-04-12 Isis Pharmaceuticals, Inc. Methods of modulating an immune response to a viral infection
RU2535993C2 (en) * 2009-03-31 2014-12-20 Дельта-Флай Фарма, Инк. Thymidilate synthase targeting rnai molecule and using it
EP2414374A4 (en) 2009-04-03 2013-09-25 Dicerna Pharmaceuticals Inc METHOD AND COMPOSITIONS FOR SPECIFIC KRAS INHIBITION WITH ASYMMETRIC DOUBLE STRAND RNA
WO2010115202A2 (en) * 2009-04-03 2010-10-07 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of kras by blunt ended double-stranded rna
ES2729261T3 (en) 2009-04-20 2019-10-31 Angiochem Inc Ovarian cancer treatment using an anticancer agent conjugated to an Angiopep-2 analog
US20120046342A1 (en) 2009-04-24 2012-02-23 Prosensa Technologies B.V. Oligonucleotide comprising an inosine for treating dmd
CA2759602A1 (en) 2009-05-05 2010-11-11 Boehringer Ingelheim International Gmbh Cho /cert cell lines
US8349808B2 (en) * 2009-05-05 2013-01-08 Medical Diagnostic Laboratories, Llc Identification of a novel repressor on IFN-lambda promoter and siRNA against ZEB1 and BLIMP-1 to increase IFN-lambda gene activity
EP2427553A4 (en) * 2009-05-06 2012-11-07 Opko Curna Llc Treatment of lipid transport and metabolism gene related diseases by inhibition of natural antisense transcript to a lipid transport and metabolism gene
KR101224828B1 (en) 2009-05-14 2013-01-22 (주)바이오니아 SiRNA conjugate and preparing method thereof
GB0908467D0 (en) * 2009-05-15 2009-06-24 Univ Gent Use of the gtpase rab27b as biomarker to stratify patients with estrogen-receptor-positive breast cancer and to monitor their disease progression
US20120114710A1 (en) * 2009-05-18 2012-05-10 Lynn Kirkpatrick Carbon nanotubes complexed with multiple bioactive agents and methods related thereto
JP2012527248A (en) * 2009-05-22 2012-11-08 クルナ・インコーポレーテッド Treatment of TFE3 and insulin receptor substrate 2 (IRS2) related diseases by inhibition of natural antisense transcripts against transcription factor E3 (TFE3)
WO2010136417A1 (en) * 2009-05-25 2010-12-02 Università Degli Studi Di Roma "La Sapienza" miR-31 IN DUCHENNE MUSCULAR DYSTROPHY THERAPY
US8493913B2 (en) * 2009-05-27 2013-07-23 Oracle International Corporation Providing session-based service orchestration to event-based networks
GB2471065A (en) * 2009-06-10 2010-12-22 Univ Sheffield Modulator of claspin for treatment of cell proliferative disorder
WO2010147992A1 (en) 2009-06-15 2010-12-23 Alnylam Pharmaceuticals, Inc. Methods for increasing efficacy of lipid formulated sirna
US8273869B2 (en) 2009-06-15 2012-09-25 Alnylam Pharmaceuticals, Inc. Lipid formulated dsRNA targeting the PCSK9 gene
KR20220084437A (en) 2009-06-17 2022-06-21 바이오젠 엠에이 인코포레이티드 Composition and methods for modulating of smn2 splicing in a subject
JP5907866B2 (en) * 2009-06-26 2016-04-26 クルナ・インコーポレーテッド Treatment of Down syndrome gene-related diseases by repression of natural antisense transcripts for Down syndrome genes
EP2449114B9 (en) 2009-07-01 2017-04-19 Protiva Biotherapeutics Inc. Novel lipid formulations for delivery of therapeutic agents to solid tumors
US9161988B2 (en) 2009-07-02 2015-10-20 Angiochem Inc. Multimeric peptide conjugates and uses thereof
IN2012DN00720A (en) 2009-07-06 2015-06-19 Ontorii Inc
US8603814B2 (en) 2009-07-20 2013-12-10 Rutgers The State University Of New Jersey Method of inhibiting nonsense-mediated mRNA decay
US9849146B2 (en) 2009-07-20 2017-12-26 Rutgers, The State University Of New Jersey Inhibition of nonsense mediated mRNA decay by drugs that prevent hypusination of eukaryotic initiation factor 5A
JP2013500017A (en) * 2009-07-24 2013-01-07 カッパーアールエヌエー，インコーポレイテッド Treatment of sirtuin (SIRT) related diseases by blocking natural antisense transcripts to sirtuin (SIRT)
WO2011019763A2 (en) * 2009-08-10 2011-02-17 The Board Of Trustees Of The University Of Illinois Compositions and methods for the treatment of krabbe and other neurodegenerative diseases
ES2599986T3 (en) * 2009-08-11 2017-02-06 Curna, Inc. Treatment of adiponectin-related diseases (ADIPOQ) by inhibiting a natural antisense transcript of an adiponectin (ADIPOQ)
CA2769822C (en) 2009-08-13 2019-02-19 The Johns Hopkins University Methods of modulating immune function
EP2810643A3 (en) 2009-08-14 2015-03-11 Alnylam Pharmaceuticals Inc. Lipid formulated compositions and mehods for inhibiting expression of a gene from the ebola virus
US8598327B2 (en) * 2009-08-18 2013-12-03 Baxter International Inc. Aptamers to tissue factor pathway inhibitor and their use as bleeding disorder therapeutics
EP2467482A4 (en) * 2009-08-21 2013-12-11 Curna Inc TREATMENT OF CHIP (C-TERMINUS OF HSP70-INTERAGING PROTEIN) CONDITIONAL DISORDERS BY INHIBITING THE NATURAL ANTISENSE TRANSCRIPT AGAINST CHIP
WO2011030329A1 (en) * 2009-09-10 2011-03-17 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Method of treating tumors
DK2475675T3 (en) 2009-09-11 2017-02-06 Ionis Pharmaceuticals Inc MODULATION OF HUNTINGTIN EXPRESSION
CN107519133A (en) 2009-09-15 2017-12-29 阿尔尼拉姆医药品有限公司 The method of the expression of composition and suppression Eg5 and VEGF genes that lipid is prepared
US9187746B2 (en) 2009-09-22 2015-11-17 Alnylam Pharmaceuticals, Inc. Dual targeting siRNA agents
CA2775092A1 (en) * 2009-09-23 2011-03-31 Protiva Biotherapeutics, Inc. Compositions and methods for silencing genes expressed in cancer
CN102028947B (en) * 2009-09-29 2014-02-05 苏州瑞博生物技术有限公司 Inhibitor, inhibitor composition and inhibiting method of FAM3B gene, fatty liver treatment method and pharmaceutical application of inhibitor
CN102869775A (en) 2009-09-30 2013-01-09 哈佛大学校长及研究员协会 Methods for modulation of autophagy through the modulation of autophagy-inhibiting gene products
US8394778B1 (en) 2009-10-08 2013-03-12 Immune Disease Institute, Inc. Regulators of NFAT and/or store-operated calcium entry
US8962584B2 (en) 2009-10-14 2015-02-24 Yissum Research Development Company Of The Hebrew University Of Jerusalem, Ltd. Compositions for controlling Varroa mites in bees
WO2011053774A1 (en) 2009-10-30 2011-05-05 Alcon Research, Ltd. Single nucleotide polymorphisms and genes associated with age-related macular degeneration
US9101643B2 (en) 2009-11-03 2015-08-11 Alnylam Pharmaceuticals, Inc. Lipid formulated compositions and methods for inhibiting expression of transthyretin (TTR)
EP2496243A2 (en) * 2009-11-04 2012-09-12 Erasmus University Medical Center Rotterdam Novel compounds for modulating neovascularisation and methods of treatment using these compounds
CN101708328A (en) * 2009-11-06 2010-05-19 上海市免疫学研究所 Pharmaceutical application of CYR61 protein
US9799416B2 (en) * 2009-11-06 2017-10-24 Terrapower, Llc Methods and systems for migrating fuel assemblies in a nuclear fission reactor
US8901097B2 (en) 2009-11-08 2014-12-02 Quark Pharmaceuticals, Inc. Methods for delivery of siRNA to the spinal cord and therapies arising therefrom
IL314343A (en) 2009-11-12 2024-09-01 Univ Western Australia Antisense oligonucleotides for inducing exon skipping in the dystrophin gene
EP2322927A1 (en) * 2009-11-16 2011-05-18 Deutsches Krebsforschungszentrum Compounds inhibiting CD95 signaling for the treatment of pancreatic cancer
CN102597239A (en) 2009-11-26 2012-07-18 夸克医药公司 Sirna compounds comprising terminal substitutions
KR101168726B1 (en) 2009-11-30 2012-07-30 한국생명공학연구원 Pharmaceutical composition for treating cancer
WO2011072082A2 (en) 2009-12-09 2011-06-16 Nitto Denko Corporation Modulation of hsp47 expression
AU2014280918B2 (en) * 2009-12-18 2016-11-17 Arrowhead Pharmaceuticals, Inc. Organic compositions to treat HSF1-related diseases
KR101718297B1 (en) * 2009-12-18 2017-03-20 애로우헤드 리서치 코오포레이션 Organic compositions to treat hsf1-related diseases
GB0922332D0 (en) 2009-12-22 2010-02-03 Isis Innovation Method of treatment and screening method
CN102781480B (en) * 2009-12-23 2018-07-27 库尔纳公司 UCP2 relevant diseases are treated by inhibiting the natural antisense transcript of uncoupling protein-3 (UCP2)
WO2011079261A2 (en) * 2009-12-23 2011-06-30 Curna, Inc. Treatment of hepatocyte growth factor (hgf) related diseases by inhibition of natural antisense transcript to hgf
CA2785451C (en) 2009-12-24 2019-01-22 Prosensa Technologies B.V. Molecule for treating an inflammatory disorder
WO2011084193A1 (en) 2010-01-07 2011-07-14 Quark Pharmaceuticals, Inc. Oligonucleotide compounds comprising non-nucleotide overhangs
CA2786071C (en) 2010-01-08 2021-01-12 Isis Pharmaceuticals, Inc. Modulation of angiopoietin-like 3 expression
NO2524039T3 (en) * 2010-01-11 2018-04-28
US20110172296A1 (en) * 2010-01-12 2011-07-14 Bennett C Frank Modulation of transforming growth factor-beta 1 expression
US9198983B2 (en) * 2010-01-25 2015-12-01 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of Mylip/Idol gene
DK2534248T3 (en) 2010-02-08 2018-11-19 Ionis Pharmaceuticals Inc SELECTIVE REDUCTION OF ALLELVARIANS
US9006198B2 (en) 2010-02-08 2015-04-14 Isis Pharmaceuticals, Inc. Selective reduction of allelic variants
WO2011106689A1 (en) * 2010-02-26 2011-09-01 Isis Pharmaceuticals, Inc. Modulation of smad3 expression
NZ627060A (en) 2010-03-08 2016-01-29 Monsanto Technology Llc Polynucleotide molecules for gene regulation in plants
RU2615143C2 (en) 2010-03-24 2017-04-04 Адвирна Self-delivered rnai compounds of reduced size
EP2550002B1 (en) 2010-03-24 2019-05-08 Phio Pharmaceuticals Corp. Rna interference in dermal and fibrotic indications
CN106074591B (en) 2010-03-24 2020-01-14 菲奥医药公司 RNA interference in ocular symptoms
US8796240B2 (en) 2010-03-26 2014-08-05 The University Of Tokyo Cell growth inhibitor and screening method thereof
US8853182B2 (en) * 2010-03-26 2014-10-07 The University Of Tokyo Cell growth inhibitor and screening method thereof
EP3329924B1 (en) 2010-03-29 2021-05-05 Alnylam Pharmaceuticals, Inc. Dsrna therapy for transthyretin (ttr) related ocular amyloidosis
WO2011127180A1 (en) * 2010-04-06 2011-10-13 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of cd274/pd-l1 gene
AU2015268740B2 (en) * 2010-04-06 2017-08-03 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of cd274/pd-l1 gene
KR20180033606A (en) 2010-04-23 2018-04-03 애로우헤드 파마슈티컬스 인코포레이티드 ORGANIC COMPOSITIONS TO TREAT BETA-ENaC-RELATED DISEASES
NZ603339A (en) 2010-04-29 2015-01-30 Isis Pharmaceuticals Inc Modulation of transthyretin expression
EP2566966A4 (en) * 2010-05-03 2013-12-11 Curna Inc Treatment of sirtuin (sirt) related diseases by inhibition of natural antisense transcript to a sirtuin (sirt)
US9226972B2 (en) * 2010-05-05 2016-01-05 Auburn University Targeted particles comprising landscape phage fusion proteins and heterologous nucleic acid
WO2011146938A1 (en) * 2010-05-21 2011-11-24 NanoOncology, Inc. Reagents and methods for treating cancer
WO2011153323A2 (en) 2010-06-02 2011-12-08 Alnylam Pharmaceuticals, Inc. Compositions and methods directed to treating liver fibrosis
RU2016118528A (en) * 2010-06-23 2018-10-31 Курна, Инк. TREATMENT OF DISEASES ASSOCIATED WITH AN ALPHA SUBNITION OF A POTENTIAL DEPENDENT SODIUM CHANNEL (SCNA), BY INHIBITING A NATURAL ANTISOUND TRANSCRIPT OF THE SCNA GENE
FR2962041B1 (en) * 2010-07-01 2012-07-27 Genethon INHIBITORS OF CALPAIN 3 FOR THE TREATMENT OF MUSCULAR DYSTROPHIES AND CARDIOMYOPATHIES
EP2591104A4 (en) 2010-07-06 2014-09-03 Dicerna Pharmaceuticals Inc METHODS AND COMPOSITIONS FOR SPECIFIC INHIBITION OF THE ANDROGEN RECEPTOR BY DOUBLE STRANDED RNA
CA2805791A1 (en) 2010-07-19 2012-01-26 Isis Pharmaceuticals, Inc. Modulation of nuclear-retained rna
KR20130095737A (en) 2010-07-28 2013-08-28 알콘 리서치, 리미티드 Sirna targeting vegfa and methods for treatment in vivo
US8455304B2 (en) 2010-07-30 2013-06-04 Atmel Corporation Routable array metal integrated circuit package fabricated using partial etching process
WO2012023288A1 (en) * 2010-08-20 2012-02-23 Oncotherapy Science, Inc. Fam161a as a target gene for cancer therapy and diagnosis
EP2609106A4 (en) * 2010-08-26 2014-03-19 Merck Sharp & Dohme RNA INTERFERENCE-MEDIATED INHIBITION OF EXPRESSION OF PHD2 GENE (PROLYL HYDROXYLASE DOMAIN 2) USING SMALL INTERFERING NUCLEIC ACID (PANI)
EP3118316A1 (en) * 2010-09-02 2017-01-18 Université de Mons Agents useful in treating facioscapulohumeral muscular dystrophy
SG10201506906VA (en) 2010-09-09 2015-10-29 Pfizer 4-1bb binding molecules
US8946186B2 (en) * 2010-09-20 2015-02-03 Arizona Board Of Regents, A Body Corporate Of The State Of Arizona Acting For And On Behalf Of Arizona State University QSOX1 as an anti-neoplastic drug target
US8217163B2 (en) * 2010-09-20 2012-07-10 Biomics Biotechnologies Co., Ltd. Application of highly conserved domain sequences from viral genome as template to design therapeutic slirnas
US20140141015A1 (en) 2010-09-20 2014-05-22 Douglas Lake QSOX1 as an Anti-Neoplastic Drug Target
JP5860038B2 (en) * 2010-09-22 2016-02-16 国立大学法人北海道大学 Nucleic acid with anti-metabolic syndrome effect
US10428019B2 (en) 2010-09-24 2019-10-01 Wave Life Sciences Ltd. Chiral auxiliaries
CA2810825A1 (en) * 2010-09-30 2012-04-05 Yoshiro Niitsu Modulation of timp1 and timp2 expression
US20120083035A1 (en) 2010-09-30 2012-04-05 Dharmacon, Inc. Modified Cell Lines for Increasing Lentiviral Titers
JP5996431B2 (en) * 2010-09-30 2016-09-21 Ｌｓｉｐファンド運営合同会社 Dominant mutant gene expression inhibitor
WO2012048316A2 (en) * 2010-10-08 2012-04-12 Immune Disease Institute, Inc. Regulators of nfat and/or store-operated calcium entry
US9637742B2 (en) 2010-10-22 2017-05-02 Sungkyunkwan University Foundation For Corporate Collaboration Nucleic acid molecules inducing RNA interference, and uses thereof
CN103201385A (en) 2010-10-27 2013-07-10 德福根有限公司 Down-regulating gene expression in insect pests
WO2012056441A1 (en) * 2010-10-28 2012-05-03 Nanodoc Ltd. Compositions and methods for specific cleavage of exogenous rna in a cell
CA2816321A1 (en) * 2010-10-29 2012-05-03 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibition of pcsk9 genes
US9150864B2 (en) 2010-11-08 2015-10-06 Isis Pharmaceuticals, Inc. Methods for modulating factor 12 expression
US9920317B2 (en) 2010-11-12 2018-03-20 The General Hospital Corporation Polycomb-associated non-coding RNAs
EP2638163B1 (en) 2010-11-12 2017-05-17 The General Hospital Corporation Polycomb-associated non-coding rnas
EP2640853B1 (en) 2010-11-17 2018-12-26 Ionis Pharmaceuticals, Inc. Modulation of alpha synuclein expression
EP2643463B1 (en) * 2010-11-23 2017-09-27 CuRNA, Inc. Treatment of nanog related diseases by inhibition of natural antisense transcript to nanog
WO2012075114A2 (en) * 2010-12-01 2012-06-07 Ablitech, Inc. Nucleic acid-polymer conjugates and uses thereof
SG190412A1 (en) * 2010-12-06 2013-06-28 Quark Pharmaceuticals Inc Double stranded oligonucleotide compounds comprising threose modifications
EP2648763A4 (en) * 2010-12-10 2014-05-14 Alnylam Pharmaceuticals Inc Compositions and methods for inhibiting expression of klf-1 and bcl11a genes
EP2649182A4 (en) * 2010-12-10 2015-05-06 Alnylam Pharmaceuticals Inc COMPOSITIONS AND METHOD FOR INCREASING AN ERYTHROPOIETIN (EPO) PREPARATION
WO2012094115A1 (en) * 2010-12-17 2012-07-12 Arrowhead Research Corporation Compositions and methods for inhibiting expression of flt3 genes
CA2820440A1 (en) * 2010-12-17 2012-06-21 Universite Pierre Et Marie Curie (Paris 6) The abcg1 gene as a marker and a target gene for treating obesity
WO2012091965A1 (en) 2010-12-17 2012-07-05 Carnegie Mellon University Electrochemically mediated atom transfer radical polymerization
ES2710109T3 (en) * 2010-12-17 2019-04-23 Inst Nat Sante Rech Med Nucleic acids that target TCTP for use in the treatment of chemoresistant or hormone-resistant cancers
US10301620B2 (en) * 2010-12-22 2019-05-28 Murdoch Childrens Research Institute Method of treatment
AU2011353283A1 (en) * 2010-12-30 2013-07-18 Samyang Biopharmaceuticals Corporation siRNA for inhibition of Hif1alpha expression and anticancer composition containing the same
CN103403543B9 (en) * 2011-01-25 2017-05-17 阿尔玛克诊断有限公司 colon cancer gene expression signatures and methods of use
TWI593416B (en) 2011-02-02 2017-08-01 艾克厘德製藥公司 Method of treating keloids or hypertrophic scars using antisense compounds targeting connective tissue growth factor (ctgf)
WO2012106175A1 (en) * 2011-02-02 2012-08-09 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Trrap and grin2a mutations and use thereof for the diagnosis and treatment of melanoma
CA2865468C (en) * 2011-03-11 2021-05-04 Sarissa Inc. Methods of treating cancer by inhibition of dna repair proteins
EP2508530A1 (en) 2011-03-28 2012-10-10 Rheinische Friedrich-Wilhelms-Universität Bonn Purification of triphosphorylated oligonucleotides using capture tags
BR112013025006B1 (en) * 2011-03-29 2021-06-15 Alnylam Pharmaceuticals, Inc PHARMACEUTICAL COMPOSITION TO INHIBIT THE EXPRESSION OF A TMPRSS6 GENE, METHOD FOR INHIBITING TMPRSS6 EXPRESSION IN A CELL, AND USE OF DOUBLE TAPE RIBONU-CLEIC ACIDS
PE20181518A1 (en) 2011-04-01 2018-09-21 Ionis Pharmaceuticals Inc MODULATION OF SIGNAL TRANSDUCER EXPRESSION AND TRANSCRIPTION ACTIVATOR 3 (STAT3)
AU2012242642A1 (en) 2011-04-13 2013-05-02 Ionis Pharmaceuticals, Inc. Antisense modulation of PTP1B expression
US10941399B2 (en) * 2011-04-14 2021-03-09 Beth Israel Deaconess Medical Center, Inc. Methods and compositions for gene-specific demethylation by DNA methyltransferase (DNMT)-RNA interaction
MX340408B (en) 2011-04-21 2016-07-07 Ionis Pharmaceuticals Inc Modulation of hepatitis b virus (hbv) expression.
TW201243330A (en) * 2011-04-22 2012-11-01 Univ Nat Cheng Kung Method for analyzing sectretome, biomarker for lung cancer metastasis, and siRNA compound for inhibiting lung cancer metastasis
US9290765B2 (en) 2011-05-02 2016-03-22 Vereniging Voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek En Patiëntenzorg Protection against endothelial barrier dysfunction through inhibition of the tyrosine kinase abl-related gene (ARG)
EP2704751B1 (en) 2011-05-02 2019-04-17 Immunomedics, Inc. Ultrafiltration concentration of allotype selected antibodies for small-volume administration
EP2717882A4 (en) * 2011-06-06 2015-03-25 Sirna Therapeutics Inc RNA INTERFERENCE-INHIBIATED INHIBITION OF ISOCITRATE DEHYDROGENASE (IDH1) GENE EXPRESSION
WO2012170771A1 (en) * 2011-06-09 2012-12-13 Curna, Inc. Treatment of frataxin (fxn) related diseases by inhibition of natural antisense transcript to fxn
WO2012170947A2 (en) 2011-06-10 2012-12-13 Isis Pharmaceuticals, Inc. Methods for modulating factor 12 expression
EP3320922A1 (en) 2011-06-10 2018-05-16 Ionis Pharmaceuticals, Inc. Methods for modulating kallikrein (klkb1) expression
AU2012271357A1 (en) 2011-06-16 2013-05-02 Ionis Pharmaceuticals, Inc. Antisense modulation of fibroblast growth factor receptor 4 expression
AU2012272970A1 (en) 2011-06-21 2014-02-06 Alnylam Pharmaceuticals, Inc. Angiopoietin-like 3 (ANGPTL3) iRNA compositions and methods of use thereof
EP2723862B1 (en) 2011-06-21 2018-09-19 MiNA Therapeutics Limited Albumin production and cell proliferation
US9068184B2 (en) 2011-06-21 2015-06-30 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibition of expression of protein C (PROC) genes
WO2012177921A2 (en) * 2011-06-21 2012-12-27 Alnylam Pharmaceuticals, Inc Compositions and methods for inhibiting hepcidin antimicrobial peptide (hamp) or hamp-related gene expression
AU2012272860A1 (en) 2011-06-21 2013-12-19 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibition of expression of apolipoprotein C-III (APOC3) genes
FI20115640A0 (en) * 2011-06-22 2011-06-22 Turun Yliopisto combination therapy
EP3597750B1 (en) * 2011-06-23 2022-05-04 Alnylam Pharmaceuticals, Inc. Serpina1 sirnas: compositions of matter and methods of treatment
US9322021B2 (en) 2011-06-29 2016-04-26 Ionis Pharmaceuticals, Inc. Methods for modulating kallikrein (KLKB1) expression
WO2013010045A1 (en) 2011-07-12 2013-01-17 Biotime Inc. Novel methods and formulations for orthopedic cell therapy
EP2734240B1 (en) 2011-07-18 2018-03-21 University Of Kentucky Research Foundation Protection of cells from alu-rna-induced degenereation and inhibitors for protecting cells
RU2014105311A (en) 2011-07-19 2015-08-27 Уэйв Лайф Сайенсес Пте. Лтд. METHODS FOR SYNTHESIS OF FUNCTIONALIZED NUCLEIC ACIDS
WO2013019857A2 (en) * 2011-08-01 2013-02-07 Alnylam Pharmaceuticals, Inc. Method for improving the success rate of hematopoietic stem cell transplants
EP3922722B1 (en) 2011-08-11 2023-06-28 Ionis Pharmaceuticals, Inc. Selective antisense compounds and uses thereof
WO2013028756A1 (en) 2011-08-22 2013-02-28 Carnegie Mellon University Atom transfer radical polymerization under biologically compatible conditions
KR101275264B1 (en) 2011-08-24 2013-06-17 포항공과대학교 산학협력단 Method of screening for chaperonin modulator
WO2013031704A1 (en) * 2011-08-29 2013-03-07 学校法人新潟科学技術学園新潟薬科大学 Heptamer-type small guide nucleic acid capable of inducing apoptosis of human leukemia cell
EP3453761A1 (en) 2011-08-29 2019-03-13 Ionis Pharmaceuticals, Inc. Oligomer-conjugate complexes and their use
EA201490553A1 (en) 2011-09-02 2014-08-29 Новартис Аг ORGANIC COMPOSITIONS FOR THE TREATMENT OF HSF1-CONNECTED DISEASES
FI20115876A0 (en) 2011-09-06 2011-09-06 Turun Yliopisto Combination therapy
WO2013036879A1 (en) * 2011-09-08 2013-03-14 Gradalis, Inc. Compositions and methods for treating prostate cancer
CN107739737A (en) 2011-09-13 2018-02-27 孟山都技术公司 Method and composition for Weeds distribution
US10806146B2 (en) 2011-09-13 2020-10-20 Monsanto Technology Llc Methods and compositions for weed control
US10760086B2 (en) 2011-09-13 2020-09-01 Monsanto Technology Llc Methods and compositions for weed control
US9416363B2 (en) 2011-09-13 2016-08-16 Monsanto Technology Llc Methods and compositions for weed control
US20130326731A1 (en) * 2011-09-13 2013-12-05 Daniel Ader Methods and compositions for weed control
EP2756086B1 (en) 2011-09-13 2018-02-21 Monsanto Technology LLC Methods and compositions for weed control
BR112014005975A8 (en) 2011-09-13 2017-09-12 Monsanto Technology Llc PLANT CONTROL METHOD, METHOD OF REDUCING EXPRESSION OF A PDS GENE IN A PLANT, MICROBIAL EXPRESSION CASSETTE, METHOD OF MAKING A POLYNUCLEOTIDE, METHOD OF IDENTIFICATION OF POLYNUCLEOTIDES, AND COMPOSITIONS FOR WEED CONTROL
US10829828B2 (en) 2011-09-13 2020-11-10 Monsanto Technology Llc Methods and compositions for weed control
BR112014005331A2 (en) * 2011-09-14 2017-04-11 Nippon Kayaku Kk methods for inhibiting cell growth, and for screening for anticancer agents, nucleic acid molecule, expression vector, composition for inhibiting gene expression, and, anticancer agent
US11058708B2 (en) * 2011-09-19 2021-07-13 Sweyshen Chen RNA interference of galectin-3 expression and methods of use thereof
CN103814132B (en) 2011-09-20 2018-06-05 苏州瑞博生物技术有限公司 Antisense regulation of GCGR expression
US9453261B2 (en) * 2011-09-20 2016-09-27 The George Washington University Alternative splicing variants of genes associated with prostate cancer risk and survival
US9481895B2 (en) 2011-09-23 2016-11-01 Ge Healthcare Dharmacon, Inc. Introduction of modular vector elements during production of a lentivirus
SG11201400976WA (en) 2011-09-28 2014-04-28 Agency Science Tech & Res Methods and pharmaceutical compositions for treating cancer
JP2013079210A (en) * 2011-10-04 2013-05-02 Nagoya City Univ Therapeutic agent, gene therapy agent, and method for preventing invasion of eosinophil
US9382534B2 (en) 2011-10-05 2016-07-05 Ge Healthcare Dharmacon, Inc. Optimization of vectors for effective delivery and expression of genetic content
CA2853373A1 (en) 2011-10-25 2013-05-02 Isis Pharmaceuticals, Inc. Antisense modulation of gccr expression
CN102373206B (en) * 2011-10-31 2013-02-27 暨南大学 PPP2R5C-siRNA799 targeted to inhibit PPP2R5C gene expression and tumor T cell proliferation and its application
EP3514798A1 (en) * 2011-10-31 2019-07-24 The Scripps Research Institute Systems and methods for genomic annotation and distributed variant interpretation
US9773091B2 (en) 2011-10-31 2017-09-26 The Scripps Research Institute Systems and methods for genomic annotation and distributed variant interpretation
EP3650544A1 (en) 2011-11-07 2020-05-13 Ionis Pharmaceuticals, Inc. Modulation of tmprss6 expression
EP2776450B1 (en) 2011-11-10 2018-04-04 Shire Human Genetic Therapies, Inc. Antisense oligonucleotide modulators of serotonin receptor 2c and uses thereof
EP2725103A3 (en) * 2011-11-14 2016-01-06 Silenseed Ltd Methods and compositions for treating prostate cancer
WO2013075140A1 (en) * 2011-11-17 2013-05-23 The United States Of America, As Represented By The Secretary, Department Of Health & Human Services Auto -recognizing therapeutic rna/dna chimeric nanoparticles (np)
SG10201912170WA (en) 2011-11-18 2020-02-27 Alnylam Pharmaceuticals Inc Rnai Agents, Compositions And Methods Of Use Thereof For Treating Transthyretin (TTR) Associated Diseases
WO2013075233A1 (en) * 2011-11-21 2013-05-30 The Royal Institution For The Advancement Of Learning / Mcgill University Method for treating brain cancer
WO2013086433A1 (en) * 2011-12-07 2013-06-13 The Methodist Hospital Research Institute Sirna compositions and methods for inhibiting gene expression in tumor initiating cells of breast cancer
CN104302768A (en) 2012-01-09 2015-01-21 诺华股份有限公司 Organic composition for treating beta-catenin related diseases
US9707235B1 (en) 2012-01-13 2017-07-18 University Of Kentucky Research Foundation Protection of cells from degeneration and treatment of geographic atrophy
WO2013112053A1 (en) 2012-01-27 2013-08-01 Prosensa Technologies B.V. Rna modulating oligonucleotides with improved characteristics for the treatment of duchenne and becker muscular dystrophy
CN104105473B (en) * 2012-02-13 2017-09-12 荷兰联合利华有限公司 skin whitening composition
SI2817287T1 (en) 2012-02-24 2019-02-28 Arbutus Biopharma Corporation Trialkyl cationic lipids and methods of use thereof
US9139829B2 (en) * 2012-02-28 2015-09-22 Medical Diagnostic Laboratories, Llc SiRNA targeting ETS1 and ELK1 and method of using same in the inhibition of CIP2A gene in cancer treatment
US9708605B2 (en) 2012-03-16 2017-07-18 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of MCL1 by double-stranded RNA
WO2013142514A1 (en) * 2012-03-19 2013-09-26 Isis Pharmaceuticals, Inc. Methods and compositions for modulating alpha-1-antitrypsin expression
US9410156B2 (en) 2012-03-28 2016-08-09 Somalogic, Inc. Aptamers to PDGF and VEGF and their use in treating PDGF and VEGF mediated conditions
WO2013149191A1 (en) * 2012-03-29 2013-10-03 The Trustees Of Columbia University In The City Of New York Methods for regulating hair growth disorders
US20150105442A1 (en) * 2012-03-29 2015-04-16 Aqua Therapeutics Co., Ltd. Nucleic Acid Molecule Capable of Inhibiting Expression of Periostin Gene, method for Inhibiting Expression of Periostin Gene, and Use of Said Nucleic Acid Molecule
AU2013202595B2 (en) 2012-03-30 2016-04-21 Biogen Ma Inc. Methods for modulating Tau expression for reducing seizure and modifying a neurodegenerative syndrome
EP2835424B1 (en) * 2012-04-03 2019-02-20 National Center For Child Health And Development DNA CONTROLLING miR-140 EXPRESSION, AND SCREENING METHOD OF DRUGS USING SAID DNA
US9133461B2 (en) 2012-04-10 2015-09-15 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the ALAS1 gene
WO2013158046A1 (en) * 2012-04-20 2013-10-24 Agency For Science, Technology And Research Rnai-based therapies for cardiomyopathies, muscular dystrophies and laminopathies
US10407677B2 (en) * 2012-04-26 2019-09-10 Intana Bioscience Gmbh High complexity siRNA pools
US9127274B2 (en) * 2012-04-26 2015-09-08 Alnylam Pharmaceuticals, Inc. Serpinc1 iRNA compositions and methods of use thereof
TWI480043B (en) * 2012-05-01 2015-04-11 Univ Kaohsiung Medical A medication for phthalates-induced estrogen receptor-negative breast cancer
BR112014027337A2 (en) * 2012-05-02 2017-07-18 Novartis Ag organic compositions for treating kras-related diseases
US9255154B2 (en) 2012-05-08 2016-02-09 Alderbio Holdings, Llc Anti-PCSK9 antibodies and use thereof
EA201492116A1 (en) 2012-05-16 2015-05-29 Рана Терапьютикс, Инк. COMPOSITIONS AND METHODS FOR MODULATING THE EXPRESSION OF MECP2
CN104540946A (en) 2012-05-16 2015-04-22 Rana医疗有限公司 Compositions and methods for modulating UTRN expression
US10059941B2 (en) 2012-05-16 2018-08-28 Translate Bio Ma, Inc. Compositions and methods for modulating SMN gene family expression
EP2850188A4 (en) 2012-05-16 2016-01-20 Rana Therapeutics Inc COMPOSITIONS AND METHODS FOR MODULATING THE EXPRESSION OF THE MULTIGENIC FAMILY OF HEMOGLOBIN
BR112014028644A2 (en) 2012-05-16 2017-08-15 Rana Therapeutics Inc COMPOSITIONS AND METHODS FOR MODULATION OF ATP2A2 EXPRESSION
US10837014B2 (en) 2012-05-16 2020-11-17 Translate Bio Ma, Inc. Compositions and methods for modulating SMN gene family expression
US20160002624A1 (en) 2012-05-17 2016-01-07 Isis Pharmaceuticals, Inc. Antisense oligonucleotide compositions
US9574193B2 (en) 2012-05-17 2017-02-21 Ionis Pharmaceuticals, Inc. Methods and compositions for modulating apolipoprotein (a) expression
US10125362B2 (en) 2012-05-22 2018-11-13 Olix Pharmaceuticals, Inc. RNA-interference-inducing nucleic acid molecule able to penetrate into cells, and use therefor
US9518261B2 (en) 2012-05-22 2016-12-13 Ionis Pharmaceuticals, Inc. Modulation of enhancer RNA mediated gene expression
CA2873828A1 (en) 2012-05-24 2013-11-28 A.B. Seeds Ltd. Naked dsrna for silencing target molecules in plant seeds
US9487780B2 (en) 2012-06-01 2016-11-08 Ionis Pharmaceuticals, Inc. Antisense compounds targeting genes associated with fibronectin
US9828602B2 (en) * 2012-06-01 2017-11-28 Ionis Pharmaceuticals, Inc. Antisense compounds targeting genes associated with fibronectin
US9201916B2 (en) * 2012-06-13 2015-12-01 Infosys Limited Method, system, and computer-readable medium for providing a scalable bio-informatics sequence search on cloud
CN102703452B (en) * 2012-06-21 2013-06-05 浙江省医学科学院 siRNA double-strand for inhibiting Bcl2 gene expression and application thereof
CN102703451B (en) * 2012-06-21 2013-04-17 浙江省医学科学院 Expression box for inhibiting expression of Bcl12 gene and vector containing expression box
BR112014031789A2 (en) * 2012-06-22 2017-08-01 Syngenta Participations Ag biological control of beetle pests
SI3461895T1 (en) 2012-06-25 2020-10-30 Ionis Pharmaceuticals, Inc. Modulation of ube3a-ats expression
SG10201610869TA (en) 2012-06-26 2017-02-27 Del Mar Pharmaceuticals Methods for treating tyrosine-kinase-inhibitor-resistant malignancies in patients with genetic polymorphisms or ahi1 dysregulations or mutations employing dianhydrogalactitol, diacetyldianhydrogalacti
WO2014009609A1 (en) 2012-07-13 2014-01-16 Turun Yliopisto Combination therapy iii
CN104661664B (en) 2012-07-13 2020-07-03 波涛生命科学有限公司 Chiral control
PL2872485T3 (en) 2012-07-13 2021-05-31 Wave Life Sciences Ltd. Asymmetric auxiliary group
CN103540655A (en) * 2012-07-16 2014-01-29 复旦大学 Application of MK5 gene for screening anti-liver cancer drug
US9604988B2 (en) 2012-07-27 2017-03-28 Riken Agent for treating or inhibiting recurrence of acute myeloid leukemia
WO2014022655A1 (en) * 2012-08-01 2014-02-06 The Trustees Of Columbia University In The City Of New York Methods for regulating hair growth disorders
KR101520383B1 (en) 2012-08-02 2015-05-15 에이비온 주식회사 Composition for Treating HPV-related Cancers
AU2013302696B9 (en) 2012-08-14 2018-08-09 Ibc Pharmaceuticals, Inc. T-cell redirecting bispecific antibodies for treatment of disease
JP6367802B2 (en) * 2012-08-30 2018-08-01 トゥルン イリオピスト How to choose individual brain cancer therapy
JP6431480B2 (en) 2012-08-31 2018-11-28 ザ ジェネラル ホスピタル コーポレイション Biotin conjugates for the treatment and diagnosis of Alzheimer's disease
US20140066595A1 (en) * 2012-09-04 2014-03-06 Thermo Fisher Scientific Biosciences Inc. Modulators of Protein Production in a Human Cell Line and Cell-free Extracts Produced Therefrom
EP2893018B1 (en) 2012-09-05 2019-07-24 Sylentis S.A.U. Sirna and their use in methods and compositions for the treatment and/or prevention of eye conditions
GB201215857D0 (en) 2012-09-05 2012-10-24 Sylentis Sau siRNA and their use in methods and compositions for the treatment and/or prevention of eye conditions
HK1210216A1 (en) 2012-09-12 2016-04-15 夸克制药公司 Double-stranded oligonucleotide molecules to p53 and methods of use thereof
AU2013224684B2 (en) * 2012-09-13 2017-07-06 Plant Bioscience Limited GENETIC MARKERS FOR Myb28
EP2712870A1 (en) 2012-09-27 2014-04-02 Rheinische Friedrich-Wilhelms-Universität Bonn Novel RIG-I ligands and methods for producing them
US20140094432A1 (en) 2012-10-02 2014-04-03 Cerulean Pharma Inc. Methods and systems for polymer precipitation and generation of particles
EP2906225B1 (en) 2012-10-11 2021-12-22 Ionis Pharmaceuticals, Inc. A modified antisense compound for use in treating kennedy's disease
US9175291B2 (en) * 2012-10-11 2015-11-03 Isis Pharmaceuticals Inc. Modulation of androgen receptor expression
US10577604B2 (en) 2012-10-15 2020-03-03 Ionis Pharmaceuticals, Inc. Methods for monitoring C9ORF72 expression
EP2906696B2 (en) 2012-10-15 2022-12-14 Ionis Pharmaceuticals, Inc. Methods for modulating c9orf72 expression
HK1212597A1 (en) 2012-10-15 2016-06-17 Isis Pharmaceuticals, Inc. Compositions for modulating c9orf72 expression
WO2014060392A1 (en) * 2012-10-16 2014-04-24 INSERM (Institut National de la Santé et de la Recherche Médicale) Caspase-6 inhibitors for treating t cell activation and/or proliferation disorders
AU2013334075B2 (en) 2012-10-26 2018-11-29 Memorial Sloan-Kettering Cancer Center Androgen receptor variants and methods for making and using
WO2014076703A1 (en) * 2012-11-14 2014-05-22 Silenseed Ltd. Methods and compositions for treating cancer
WO2014077693A1 (en) * 2012-11-16 2014-05-22 Academisch Ziekenhuis Leiden H.O.D.N. Lumc Means and methods for reducing an effect of aging in a mammalian cell
ES2884925T3 (en) 2012-11-27 2021-12-13 Childrens Medical Ct Corp Distal regulatory elements of BCL11A as targets for fetal hemoglobin reinduction
EP4083209A1 (en) 2012-12-05 2022-11-02 Alnylam Pharmaceuticals, Inc. Pcsk9 irna compositions and methods of use thereof
WO2014093746A2 (en) * 2012-12-14 2014-06-19 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of ckap5 by double-stranded rna
US10683505B2 (en) 2013-01-01 2020-06-16 Monsanto Technology Llc Methods of introducing dsRNA to plant seeds for modulating gene expression
WO2014106837A2 (en) 2013-01-01 2014-07-10 A. B. Seeds Ltd. ISOLATED dsRNA MOLECULES AND METHODS OF USING SAME FOR SILENCING TARGET MOLECULES OF INTEREST
EP2943225A4 (en) 2013-01-09 2016-07-13 Ionis Pharmaceuticals Inc Compositions and methods for modulation of smn2 splicing in a subject
WO2014113431A2 (en) * 2013-01-15 2014-07-24 Tufts Medical Center Methods and compositions for targeting immunoglobulins
KR101409445B1 (en) * 2013-01-17 2014-06-24 한국과학기술연구원 siRNA for Inhibition of OTUB1 Expression and Pharmaceutical Composition Containing the same
KR101480523B1 (en) * 2013-02-07 2015-01-08 고려대학교 산학협력단 siRNA for Inhibiting Endogenous rpS3 Expression
ES2961686T3 (en) 2013-02-14 2024-03-13 Ionis Pharmaceuticals Inc Modulation of apolipoprotein C-III (APOCIII) expression in lipoprotein lipase deficient (LPLD) populations
DE102013003869B4 (en) * 2013-02-27 2016-11-24 Friedrich-Schiller-Universität Jena A method for the targeted killing of cells by mRNA binding aligned nucleotide molecules and nucleotide molecules and application kit for such use
US9868949B2 (en) 2013-02-28 2018-01-16 Arrowhead Pharmaceuticals, Inc. Organic compositions to treat EPAS1-related diseases
US9265789B2 (en) * 2013-03-12 2016-02-23 The Medical College Of Wisconsin, Inc. Targeting CLPTM1L by RNA interference for treatment and prevention of cancer
US10609930B2 (en) 2013-03-13 2020-04-07 Monsanto Technology Llc Methods and compositions for weed control
CN105263329B (en) 2013-03-13 2020-09-18 孟山都技术公司 Methods and compositions for weed control
EP2971183A4 (en) 2013-03-13 2016-10-26 Meso Scale Technologies Llc Improved assay methods
US20160138027A1 (en) * 2013-03-14 2016-05-19 The Board Of Trustees Of The Leland Stanford Junior University Treatment of diseases and conditions associated with dysregulation of mammalian target of rapamycin complex 1 (mtorc1)
US9644207B2 (en) 2013-03-14 2017-05-09 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating Tau expression
NZ631245A (en) 2013-03-14 2017-09-29 Sarepta Therapeutics Inc Exon skipping compositions for treating muscular dystrophy
SG10201700239UA (en) 2013-03-14 2017-02-27 Alnylam Pharmaceuticals Inc COMPLEMENT COMPONENT C5 iRNA COMPOSITIONS AND METHODS OF USE THEREOF
US20140288149A1 (en) 2013-03-15 2014-09-25 Graham Lord Mir-142 and antagonists thereof for treating disease
US10235496B2 (en) 2013-03-15 2019-03-19 The Scripps Research Institute Systems and methods for genomic annotation and distributed variant interpretation
US11342048B2 (en) 2013-03-15 2022-05-24 The Scripps Research Institute Systems and methods for genomic annotation and distributed variant interpretation
US9132174B2 (en) 2013-03-15 2015-09-15 Anchored Rsk3 Inhibitors, Llc Treatment of heart disease by inhibition of the action of ribosomal S6 kinase 3 (RSK3)
US9506058B2 (en) 2013-03-15 2016-11-29 Sarepta Therapeutics, Inc. Compositions for treating muscular dystrophy
US9418203B2 (en) 2013-03-15 2016-08-16 Cypher Genomics, Inc. Systems and methods for genomic variant annotation
US10568328B2 (en) 2013-03-15 2020-02-25 Monsanto Technology Llc Methods and compositions for weed control
US10059944B2 (en) 2013-03-15 2018-08-28 New York University SiRNA targeting HSR1
CA2906663A1 (en) * 2013-03-15 2014-09-18 Techulon Inc. Antisense molecules for treatment of staphylococcus aureus infection
US20160051693A1 (en) 2013-03-21 2016-02-25 Genisphere, Llc Cellular Delivery of DNA Intercalating Agents
JP5976922B2 (en) * 2013-03-21 2016-08-24 学校法人 埼玉医科大学 Double-stranded nucleic acid molecule, DNA, vector, cancer cell growth inhibitor, and medicine
CN103205400B (en) * 2013-04-19 2014-09-17 青岛大学医学院附属医院 Recombinant lentiviral vector containing ubiquitin-specific protease gene USP39-shRNA (short hairpin ribonucleic acid) and application thereof
US9264644B2 (en) * 2013-04-25 2016-02-16 Forza Silicon Corporation Analog-to-digital conversion for image sensor with non-destructive read pixel
RU2670614C9 (en) 2013-05-01 2018-11-23 Ионис Фармасьютикалз, Инк. Compositions and methods for modulating hbv and ttr expression
EP2991686A4 (en) 2013-05-03 2017-04-05 President and Fellows of Harvard College Foreign dna surveillance protein
MY176712A (en) 2013-05-22 2020-08-19 Alnylam Pharmaceuticals Inc Serpina1 irna compositions and methods of use thereof
EP3587578A1 (en) 2013-05-22 2020-01-01 Alnylam Pharmaceuticals, Inc. Tmprss6 irna compositions and methods of use thereof
EP2999783A2 (en) * 2013-05-23 2016-03-30 University of Bremen Novel treatment of metabolic diseases
US9790504B2 (en) * 2013-05-24 2017-10-17 The University Of Chicago Anti-tumor therapy
JP2016524621A (en) 2013-06-03 2016-08-18 バル−イラン ユニバーシティ Liposomes that modulate Wiscot Aldrich syndrome protein
JP6529486B2 (en) * 2013-06-05 2019-06-12 バイオタイム インク．Ｂｉｏｔｉｍｅ Ｉｎｃ． Compositions and methods for induced tissue regeneration in mammalian species
PT3444350T (en) 2013-07-03 2022-02-04 Dicerna Pharmaceuticals Inc Methods and compositions for the specific inhibition of alpha-1 antitrypsin by double-stranded rna
KR102306656B1 (en) * 2013-07-03 2021-09-29 삼성전자주식회사 Combination therapy for the treatment of cancer using an anti-c-Met antibody
US9512430B2 (en) 2013-07-03 2016-12-06 Wisconsin Alumni Research Foundation Compositions and methods to promote erythropoiesis
KR20150006743A (en) * 2013-07-09 2015-01-19 (주)바이오니아 Liver cancer related genes-specific siRNA, double-stranded oligo RNA molecules comprising the siRNA, and composition for the prevention or treatment of cancer comprising the same
KR20150006742A (en) * 2013-07-09 2015-01-19 (주)바이오니아 Liver cancer related genes-specific siRNA, double-stranded oligo RNA molecules comprising the siRNA, and composition for the prevention or treatment of cancer comprising the same
TWI657819B (en) 2013-07-19 2019-05-01 美商Ionis製藥公司 Composition for regulating the expression of tau protein
CN105980567B (en) 2013-07-19 2021-04-16 孟山都技术有限公司 Compositions and methods for controlling Beetle
US9850496B2 (en) 2013-07-19 2017-12-26 Monsanto Technology Llc Compositions and methods for controlling Leptinotarsa
TW201536329A (en) 2013-08-09 2015-10-01 Isis Pharmaceuticals Inc Compound and method for regulating the manifestation of dystrophic myotonic protein kinase (DMPK)
BR112016003127A2 (en) * 2013-08-16 2017-10-17 Rana Therapeutics Inc “COMPOSITIONS AND METHODS TO MODULATE RNA”
US10144928B2 (en) 2013-08-23 2018-12-04 Quark Pharmaceuticals, Inc. Double stranded oligonucleotide compounds comprising positional modifications
ES2790574T3 (en) * 2013-08-28 2020-10-28 Ionis Pharmaceuticals Inc Prekallikrein expression modulation (PKK)
KR20210088009A (en) * 2013-09-05 2021-07-13 사렙타 쎄러퓨틱스, 인코퍼레이티드 Antisense-induced exon2 inclusion in acid alpha-glucosidase
EP3041861B1 (en) * 2013-09-05 2019-03-27 Inis Biotech LLC Sparc (secreted protein, acidic and rich in cysteine), a new target for the treatment and prevention of acute liver failure
EP3044334B1 (en) * 2013-09-09 2020-08-12 Somalogic, Inc. Pdgf and vegf aptamers having improved stability and their use in treating pdgf and vegf mediated diseases and disorders
DK3043827T3 (en) * 2013-09-13 2019-08-26 Ionis Pharmaceuticals Inc MODULATORS OF COMPLEMENT FACTOR B
EP2853596A1 (en) * 2013-09-30 2015-04-01 IKBT (Institut für Klinische Biomedizinische Forschung Thurgau) Protein phosphatase inhibitor
CN105793423A (en) * 2013-10-02 2016-07-20 阿尔尼拉姆医药品有限公司 Compositions and methods for inhibiting LECT2 gene expression
CA2959482A1 (en) * 2013-10-02 2015-04-09 Albert Einstein College Of Medicine, Inc. Methods and compositions to inhibit metastasis
HUE049227T2 (en) * 2013-10-04 2020-09-28 Alnylam Pharmaceuticals Inc Compositions and methods for inhibiting ALAS1 gene expression
EP4166667A3 (en) 2013-10-11 2023-08-02 Ionis Pharmaceuticals, Inc. Compositions for modulating c9orf72 expression
US11162096B2 (en) 2013-10-14 2021-11-02 Ionis Pharmaceuticals, Inc Methods for modulating expression of C9ORF72 antisense transcript
EP2865757A1 (en) * 2013-10-22 2015-04-29 Sylentis, S.A.U. siRNA and their use in methods and compositions for inhibiting the expression of the PDK1 gene.
EP2865758A1 (en) * 2013-10-22 2015-04-29 Sylentis, S.A.U. siRNA and their use in methods and compositions for inhibiting the expression of the ORAI1 gene
ES3008698T3 (en) 2013-11-04 2025-03-24 Greenlight Biosciences Inc Compositions and methods for controlling arthropod parasite and pest infestations
WO2015070158A1 (en) * 2013-11-11 2015-05-14 Sirna Therapeutics, Inc. Systemic delivery of myostatin short interfering nucleic acids (sina) conjugated to a lipophilic moiety
US10202601B2 (en) 2013-11-22 2019-02-12 Mina Therapeutics Limited C/EBPα short activating RNA compositions and methods of use
JP6772062B2 (en) 2013-12-02 2020-10-21 フィオ ファーマシューティカルズ コーポレーションＰｈｉｏ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｃｏｒｐ． Cancer immunotherapy
WO2015085158A1 (en) 2013-12-06 2015-06-11 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of transthyretin (ttr) by double-stranded rna
UA119253C2 (en) 2013-12-10 2019-05-27 Біолоджикс, Інк. METHOD FOR VARROA TREATMENT AND VEGETABLES
EP3798306A1 (en) 2013-12-12 2021-03-31 Alnylam Pharmaceuticals, Inc. Complement component irna compositions and methods of use thereof
CN105814204B (en) 2013-12-24 2020-04-28 Ionis制药公司 Modulation of angiopoietin-like 3 expression
DK3581654T3 (en) 2013-12-27 2021-04-26 Dicerna Pharmaceuticals Inc PROCEDURES AND COMPOSITIONS FOR SPECIFIC INHIBITION OF GLYCOLATOXIDASE (HAO1) BY DOUBLE-STRANDED RNA
BR112016016337A2 (en) 2014-01-15 2017-10-03 Monsanto Technology Llc COMPOSITION AND METHODS FOR CONTROLLING THE GROWTH, DEVELOPMENT OR REPRODUCTION ABILITY OF A PLANT, AND FOR SENSITIZING A PLANT TO AN EPSPS-INHIBITOR HERBICIDIER
US10149905B2 (en) 2014-01-15 2018-12-11 Shin Nippon Biomedical Laboratories, Ltd. Chiral nucleic acid adjuvant having antitumor effect and antitumor agent
WO2015108047A1 (en) 2014-01-15 2015-07-23 株式会社新日本科学 Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator
CA2936712A1 (en) 2014-01-16 2015-07-23 Meena Chiral design
CN104805085A (en) * 2014-01-29 2015-07-29 江苏命码生物科技有限公司 Tandem expressed siRNA and use of tandem expressed siRNA in treatment on chronic lymphocytic leukemia
JP6594902B2 (en) 2014-02-11 2019-10-23 アルナイラム ファーマシューティカルズ， インコーポレイテッド Keto hexokinase (KHK) iRNA compositions and methods of use thereof
US11078462B2 (en) 2014-02-18 2021-08-03 ReCyte Therapeutics, Inc. Perivascular stromal cells from primate pluripotent stem cells
KR101425140B1 (en) * 2014-02-19 2014-08-13 한국과학기술원 Inhibitors of methylation of LIN28A for controlling differentiation of pluripotent stem cells, its screening method and Compositions of the same
CN106132436B (en) 2014-02-21 2021-06-15 Ibc药品公司 Disease therapy by inducing an immune response to TROP-2 expressing cells
CA2935748A1 (en) 2014-02-25 2015-09-03 Immunomedics, Inc. Humanized rfb4 anti-cd22 antibody
US10011837B2 (en) 2014-03-04 2018-07-03 Sylentis Sau SiRNAs and their use in methods and compositions for the treatment and/or prevention of eye conditions
CN104894223B (en) * 2014-03-07 2019-03-26 上海吉凯基因化学技术有限公司 The purposes and its related drugs of people's COPB2 gene
JPWO2015137459A1 (en) * 2014-03-13 2017-04-06 協和発酵キリン株式会社 Nucleic acids that suppress IRF5 expression
US10280418B2 (en) 2014-03-18 2019-05-07 Univeristy Of Massachusetts RAAV-based compositions and methods for treating amyotrophic lateral sclerosis
LT3119888T (en) * 2014-03-19 2021-10-11 Ionis Pharmaceuticals, Inc. Compositions for modulating ataxin 2 expression
US10006027B2 (en) 2014-03-19 2018-06-26 Ionis Pharmaceuticals, Inc. Methods for modulating Ataxin 2 expression
US20170137808A1 (en) * 2014-03-20 2017-05-18 Oommen Varghese Improved small interfering ribonucleic acid molecules
JP6622214B2 (en) 2014-04-01 2019-12-18 バイオジェン・エムエイ・インコーポレイテッドＢｉｏｇｅｎ ＭＡ Ｉｎｃ． Composition for modulating SOD-1 expression
BR112016022711A2 (en) 2014-04-01 2017-10-31 Monsanto Technology Llc compositions and methods for insect pest control
JP6426268B2 (en) * 2014-04-04 2018-11-21 バイオニア コーポレーションＢｉｏｎｅｅｒ Ｃｏｒｐｏｒａｔｉｏｎ Novel double helix oligo RNA and pharmaceutical composition for preventing or treating fibrosis or respiratory disease comprising the same
ES2932304T3 (en) 2014-04-17 2023-01-17 Biogen Ma Inc Compositions and methods for modulation of SMN2 splicing in a subject
KR102390629B1 (en) 2014-04-25 2022-04-26 칠드런'즈 메디컬 센터 코포레이션 Compositions and methods to treating hemoglobinopathies
EP3137119B1 (en) 2014-04-28 2020-07-01 Phio Pharmaceuticals Corp. Methods for treating cancer using a nucleic acid targeting mdm2
WO2015168532A2 (en) 2014-05-01 2015-11-05 Isis Pharmaceuticals, Inc. Compositions and methods for modulating pkk expression
WO2015168618A2 (en) 2014-05-01 2015-11-05 Isis Pharmaceuticals, Inc. Compositions and methods for modulating growth hormone receptor expression
AU2015252858C1 (en) * 2014-05-01 2021-09-16 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating Complement Factor B expression
PT3137605T (en) 2014-05-01 2020-12-18 Ionis Pharmaceuticals Inc Compositions and methods for modulating angiopoietin-like 3 expression
KR20250011724A (en) 2014-05-15 2025-01-21 메소 스케일 테크놀러지즈, 엘엘시 Improved assay methods
HUE046546T2 (en) * 2014-05-23 2020-03-30 Univ Degli Studi Dellaquila Small interfering rna (sirna) for the therapy of type 2 (ado2) autosomal dominant osteopetrosis caused by clcn7 (ado2 clcn7-dependent) gene mutation
KR20150137473A (en) * 2014-05-29 2015-12-09 한국과학기술연구원 siRNA for Inhibition of USP15 Expression and Pharmaceutical Composition Containing the same
JPWO2015186770A1 (en) 2014-06-04 2017-04-20 協和発酵キリン株式会社 CCAP5 gene expression-suppressing RNAi pharmaceutical composition
TW201620526A (en) 2014-06-17 2016-06-16 愛羅海德研究公司 Composition and method for inhibiting α-1 antitrypsin gene expression
US10988764B2 (en) 2014-06-23 2021-04-27 Monsanto Technology Llc Compositions and methods for regulating gene expression via RNA interference
EP3161138A4 (en) 2014-06-25 2017-12-06 Monsanto Technology LLC Methods and compositions for delivering nucleic acids to plant cells and regulating gene expression
US10240127B2 (en) 2014-07-03 2019-03-26 ReCyte Therapeutics, Inc. Exosomes from clonal progenitor cells
RU2021123470A (en) 2014-07-29 2021-09-06 Монсанто Текнолоджи Ллс COMPOSITIONS AND METHODS FOR COMBATING PESTS
US9752144B2 (en) * 2014-08-04 2017-09-05 MiRagen Therapeutics, Inc. Inhibitors of MYH7B and uses thereof
US20170137820A1 (en) * 2014-08-06 2017-05-18 Bavarian Nordic A/S Agonists and antagonists of toll-like receptor (tlr) 13
AU2015304945B2 (en) * 2014-08-20 2022-04-07 Lifesplice Pharma Llc Splice modulating oligonucleotides and methods of use thereof
EP4043567B1 (en) * 2014-08-29 2024-05-08 The Children's Medical Center Corporation Methods and compositions for the treatment of cancer
HUE059857T2 (en) 2014-08-29 2023-01-28 Alnylam Pharmaceuticals Inc Patisiran for use in treating transthyretin mediated amyloidosis
US10731163B2 (en) * 2014-09-02 2020-08-04 Max-Delbrück-Centrum Für Molekulare Medizin In Der Helmholtz-Gemeinschaft Oligonucleotide targeted to the A20-3′ untranslated region
US10900039B2 (en) * 2014-09-05 2021-01-26 Phio Pharmaceuticals Corp. Methods for treating aging and skin disorders using nucleic acids targeting Tyr or MMP1
WO2016040167A1 (en) * 2014-09-08 2016-03-17 Brandon Higgs Compositions and methods for detecting and treating small cell lung cancer
WO2016040589A1 (en) 2014-09-12 2016-03-17 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting complement component c5 and methods of use thereof
BR112017004056A2 (en) 2014-09-12 2017-12-05 Biogen Ma Inc compositions and methods for detecting smn protein in an individual and treating an individual
WO2016041058A1 (en) * 2014-09-18 2016-03-24 The University Of British Columbia Allele-specific therapy for huntington disease haplotypes
US9777279B2 (en) * 2014-09-24 2017-10-03 University Of Cincinnati Methods and compositions for treating autoimmune disorders by targeting Kv1.3 ion channels with functionalized lipid-derived nanovesicles
JOP20200115A1 (en) 2014-10-10 2017-06-16 Alnylam Pharmaceuticals Inc Compositions And Methods For Inhibition Of HAO1 (Hydroxyacid Oxidase 1 (Glycolate Oxidase)) Gene Expression
WO2016061487A1 (en) * 2014-10-17 2016-04-21 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting aminolevulinic acid synthase-1 (alas1) and uses thereof
KR101646609B1 (en) * 2014-10-24 2016-08-08 한국원자력의학원 Composition for diagnosing laryngeal cancer or radio resistance of laryngeal cancer and diagnosing method
WO2016069694A2 (en) 2014-10-30 2016-05-06 Alnylam Pharmaceuticals, Inc. Polynucleotide agents targeting serpinc1 (at3) and methods of use thereof
WO2016070060A1 (en) 2014-10-30 2016-05-06 The General Hospital Corporation Methods for modulating atrx-dependent gene repression
US10302644B2 (en) * 2014-11-04 2019-05-28 Dana-Farber Cancer Institute, Inc. Compositions and methods for treating multiple myeloma
JOP20200092A1 (en) * 2014-11-10 2017-06-16 Alnylam Pharmaceuticals Inc HEPATITIS B VIRUS (HBV) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
WO2016077566A1 (en) * 2014-11-12 2016-05-19 Research Institute At Nationwide Children's Hospital Modulation of alternative mdm2 splicing
US10287584B2 (en) * 2014-11-12 2019-05-14 Ionis Pharmaceuticals, Inc. Compounds and methods for the modulation of COMP
SG11201703281RA (en) 2014-11-14 2017-05-30 Voyager Therapeutics Inc Compositions and methods of treating amyotrophic lateral sclerosis (als)
WO2016077704A1 (en) 2014-11-14 2016-05-19 The Regents Of The University Of California Modulation of agpat5 expression
HK1244843A1 (en) 2014-11-17 2018-08-17 Alnylam Pharmaceuticals, Inc. Apolipoprotein c3 (apoc3) irna compositions and methods of use thereof
WO2016085852A1 (en) 2014-11-24 2016-06-02 Alnylam Pharmaceuticals, Inc. Tmprss6 irna compositions and methods of use thereof
WO2016086104A1 (en) 2014-11-25 2016-06-02 Ionis Pharmaceuticals, Inc. Modulation of ube3a-ats expression
CN104450710B (en) * 2014-11-28 2018-06-05 广州市锐博生物科技有限公司 Inhibit nucleic acid oligomer and its application of MYD88 genes
US9714424B1 (en) * 2014-12-16 2017-07-25 Icahn School Of Medicine At Mount Sinai RNAi inhibition of USP10 to treat ocular disorders
ES2726674T3 (en) * 2014-12-23 2019-10-08 Syngenta Participations Ag Biological control of beetle pests
US10774326B2 (en) * 2014-12-24 2020-09-15 Massachusetts Institute Of Technology Compositions and methods for manipulation of adipocyte energy consumption regulatory pathway
JP6706628B2 (en) * 2014-12-25 2020-06-10 クワンチョウ リボバイオ カンパニー リミテッドＧｕａｎｇｚｈｏｕ Ｒｉｂｏｂｉｏ Ｃｏ．，Ｌｔｄ． Composition for suppressing expression of ADAMTS-5 or ADAMTS and method thereof
US11045488B2 (en) 2014-12-26 2021-06-29 Nitto Denko Corporation RNA interference agents for GST-π gene modulation
US10792299B2 (en) 2014-12-26 2020-10-06 Nitto Denko Corporation Methods and compositions for treating malignant tumors associated with kras mutation
US20180002702A1 (en) 2014-12-26 2018-01-04 Nitto Denko Corporation Methods and compositions for treating malignant tumors associated with kras mutation
US10264976B2 (en) * 2014-12-26 2019-04-23 The University Of Akron Biocompatible flavonoid compounds for organelle and cell imaging
WO2016112132A1 (en) * 2015-01-06 2016-07-14 Ionis Pharmaceuticals, Inc. Compositions for modulating expression of c9orf72 antisense transcript
US9982070B2 (en) 2015-01-12 2018-05-29 Carnegie Mellon University Aqueous ATRP in the presence of an activator regenerator
WO2016115490A1 (en) 2015-01-16 2016-07-21 Ionis Pharmaceuticals, Inc. Compounds and methods for modulation of dux4
US9434947B2 (en) * 2015-01-20 2016-09-06 Oregon Health & Science University Modulation of KCNH2 isoform expression by oligonucleotides as a therapeutic approach for long QT syndrome
EP3256589B1 (en) 2015-01-22 2021-12-22 Monsanto Technology LLC Compositions and methods for controlling leptinotarsa
CA2976445A1 (en) * 2015-02-13 2016-08-18 Alnylam Pharmaceuticals, Inc. Patatin-like phospholipase domain containing 3 (pnpla3) irna compositions and methods of use thereof
WO2016130943A1 (en) 2015-02-13 2016-08-18 Rana Therapeutics, Inc. Hybrid oligonucleotides and uses thereof
US10036017B2 (en) 2015-02-17 2018-07-31 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of complement component 5(C5) by double-stranded RNA
US10525076B2 (en) 2015-02-20 2020-01-07 Rosalind Franklin University Of Medicine And Science Antisense compounds targeting genes associated with cystic fibrosis
EP3259356B1 (en) * 2015-02-20 2021-12-01 Rosalind Franklin University of Medicine and Science Antisense compounds targeting genes associated with cystic fibrosis
WO2016137937A1 (en) * 2015-02-24 2016-09-01 Dcb-Usa Llc Short interfering rna for treating cancer
ES2848377T3 (en) 2015-02-26 2021-08-09 Ionis Pharmaceuticals Inc Allele-specific modulators of RHODOPSIN P23H
US11129844B2 (en) 2015-03-03 2021-09-28 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating MECP2 expression
WO2016149455A2 (en) 2015-03-17 2016-09-22 The General Hospital Corporation The rna interactome of polycomb repressive complex 1 (prc1)
BR112017018029B1 (en) 2015-03-20 2021-06-15 Unilever Ip Holdings B.V. SIRNA MOLECULE, METHOD FOR REDUCING PERSPIRATION, ANTIPERSPIRATING COMPOSITION AND USE OF AN ANTIPERSPIRATING COMPOSITION
EP3072969A1 (en) * 2015-03-23 2016-09-28 DKFZ Deutsches Krebsforschungszentrum, Stiftung des öffentlichen Rechts Oligonucleotide sequences targeting transcription factor TSC22D4 for the treatment of insulin resistance
WO2016154629A1 (en) 2015-03-26 2016-09-29 Woman & Infants' Hospital Of Rhode Island Therapy for malignant disease
US20180371523A1 (en) * 2015-04-01 2018-12-27 Institute Of Environmental Science And Research Methods and materials for detecting rna sequences
JP6892433B2 (en) 2015-04-03 2021-06-23 ユニバーシティ・オブ・マサチューセッツＵｎｉｖｅｒｓｉｔｙ Ｏｆ Ｍａｓｓａｃｈｕｓｅｔｔｓ Well-stabilized asymmetric SIRNA
PL3277815T3 (en) 2015-04-03 2022-03-21 University Of Massachusetts Oligonucleotide compounds for treatment of preeclampsia and other angiogenic disorders
ES2808750T3 (en) * 2015-04-03 2021-03-01 Univ Massachusetts Oligonucleotide compounds targeting huntingtin mRNA
MX2017012426A (en) 2015-04-03 2018-01-26 Ionis Pharmaceuticals Inc Compounds and methods for modulating tmprss6 expression.
US10745702B2 (en) 2015-04-08 2020-08-18 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of the LECT2 gene
MX392757B (en) 2015-04-13 2025-03-24 Alnylam Pharmaceuticals Inc ANGIOPOETIN TYPE 3 (ANGPTL3) INTERFERENCE RIBONUCLEIC ACID (RNAI) COMPOSITIONS AND METHOD OF USING THE SAME.
SG10202001856WA (en) 2015-04-16 2020-04-29 Ionis Pharmaceuticals Inc Compositions for modulating c9orf72 expression
CN107530439B (en) * 2015-04-17 2021-06-18 詹尼斯费尔公司 siRNA inhibition of human antigen R expression for the treatment of cancer
EP3286318A2 (en) * 2015-04-22 2018-02-28 Mina Therapeutics Limited Sarna compositions and methods of use
ES2835861T5 (en) 2015-05-08 2025-02-18 Childrens Medical Ct Corp Targeting bcl11a enhancer functional regions for fetal hemoglobin reinduction
CN108174607A (en) 2015-05-29 2018-06-15 朱诺治疗学股份有限公司 Compositions and methods for modulating inhibitory interactions in genetically engineered cells
WO2016196738A1 (en) 2015-06-02 2016-12-08 Monsanto Technology Llc Compositions and methods for delivery of a polynucleotide into a plant
EP3302030A4 (en) 2015-06-03 2019-04-24 Monsanto Technology LLC METHODS AND COMPOSITIONS FOR THE INTRODUCTION OF NUCLEIC ACIDS IN PLANTS
ES2826827T3 (en) 2015-06-15 2021-05-19 Angiochem Inc Methods for the treatment of leptomeningeal carcinomatosis
WO2016209862A1 (en) * 2015-06-23 2016-12-29 Alnylam Pharmaceuticals, Inc. Glucokinase (gck) irna compositions and methods of use thereof
US10874622B2 (en) 2015-06-24 2020-12-29 Board Of Regents, The University Of Texas System Dual assembly nanoparticles
EP3112466A1 (en) * 2015-07-01 2017-01-04 Samsung Electronics Co., Ltd. Composition for reducing cellular senescence level including activity inhibitor inhibiting dcun1d3 activity or expression inhibitor inhibiting expression of dcun1d3-encoding gene and use thereof
WO2017007825A1 (en) 2015-07-06 2017-01-12 Rxi Pharmaceuticals Corporation Methods for treating neurological disorders using a synergistic small molecule and nucleic acids therapeutic approach
US11001845B2 (en) 2015-07-06 2021-05-11 Phio Pharmaceuticals Corp. Nucleic acid molecules targeting superoxide dismutase 1 (SOD1)
MY192997A (en) 2015-07-10 2022-09-20 Ionis Pharmaceuticals Inc Modulators of diacyglycerol acyltransferase 2 (dgat2)
WO2017011286A1 (en) * 2015-07-10 2017-01-19 Alnylam Pharmaceuticals, Inc. Insulin-like growth factor binding protein, acid labile subunit (igfals) and insulin-like growth factor 1 (igf-1) irna compositions and methods of use thereof
TW201713769A (en) * 2015-07-13 2017-04-16 Kyowa Hakko Kirin Co Ltd ANTISENSE OLIGONUCLEOTIDE INHIBITING [beta]2GPI EXPRESSION
US20170051282A1 (en) * 2015-07-23 2017-02-23 Cold Spring Harbor Laboratory Extracellular vesicle methods and compositions
US20180216114A1 (en) * 2015-07-27 2018-08-02 Alnylam Pharmaceuticals, Inc. Xanthine dehydrogenase (xdh) irna compositions and methods of use thereof
EP3328878A1 (en) 2015-07-30 2018-06-06 Bayer CropScience Aktiengesellschaft Methods and compositions for the control of rust fungi by inhibiting expression of the hxt1 gene
HK1256683A1 (en) 2015-07-31 2019-10-04 阿尔尼拉姆医药品有限公司 Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated diseases
CN105063048A (en) * 2015-08-13 2015-11-18 吉林大学 SiRNA (small interfering ribonucleic acid) capable of inhibiting expression of Survivin genes and application of siRNA
US10633653B2 (en) 2015-08-14 2020-04-28 University Of Massachusetts Bioactive conjugates for oligonucleotide delivery
US10709726B2 (en) * 2015-08-14 2020-07-14 The University Of Sydney Connexin 45 inhibition for therapy
CN106467914A (en) * 2015-08-18 2017-03-01 华东理工大学 The siRNA of targeting people's TSPAN8 gene and its application
WO2017029391A1 (en) * 2015-08-20 2017-02-23 INSERM (Institut National de la Santé et de la Recherche Médicale) New method for treating cancer
NZ779375A (en) 2015-08-25 2025-05-30 Alnylam Pharmaceuticals Inc Methods and compositions for treating a proprotein convertase subtilisin kexin (pcsk9) gene-associated disorder
PE20181131A1 (en) 2015-09-02 2018-07-17 Alnylam Pharmaceuticals Inc RNAi COMPOSITIONS FOR PROGRAMMED CELL DEATH 1 (PD-L1) LINK 1 (PD-L1) AND METHODS OF USE OF THEM
MA44908A (en) * 2015-09-08 2018-07-18 Sylentis Sau ARNSI MOLECULES AND THEIR USE IN PROCESSES AND COMPOSITIONS TO INHIBIT NRARP GENE EXPRESSION
WO2017042239A1 (en) * 2015-09-08 2017-03-16 Sylentis Sau siRNA and their use in methods and compositions for inhibiting the expression of the CHI3L1 gene
GB201516685D0 (en) * 2015-09-21 2015-11-04 Varghese Oommen P And Oommen Oommen P Nucleic acid molecules with enhanced activity
US10584315B2 (en) 2015-09-24 2020-03-10 Wisconsin Alumni Research Foundation Methods of expanding hematopoietic stem cells, compositions, and methods of use thereof
EP4285912A3 (en) 2015-09-25 2024-07-10 Ionis Pharmaceuticals, Inc. Compositions and methods for modulating ataxin 3 expression
CN106554962B (en) * 2015-09-30 2021-06-04 中国科学院上海药物研究所 Prevention, diagnosis and treatment of cancers overexpressing GPR160
WO2017062422A1 (en) 2015-10-07 2017-04-13 The Research Foundation For The State University Of New York METHODS FOR INCREASING PLATELET COUNT BY INHIBITING BILIVERDIN IXβ REDUCTASE
SG10202003148VA (en) 2015-10-08 2020-05-28 Ionis Pharmaceuticals Inc Compounds and methods for modulating angiotensinogen expression
JP2018531046A (en) * 2015-10-14 2018-10-25 アクイナ ファーマシューティカルズ， インコーポレイテッド Nucleic acid based TIA-1 inhibitors
US10682362B2 (en) 2015-10-14 2020-06-16 Wayne State University Treatments and diagnostics for cancers
WO2017066643A1 (en) 2015-10-14 2017-04-20 Bio-Path Holding, Inc. P-ethoxy nucleic acids for liposomal formulation
KR101842679B1 (en) * 2015-10-15 2018-03-28 한국과학기술원 Rna oligonucleotide and enhancer of immune system comprising the same
WO2017065369A1 (en) * 2015-10-15 2017-04-20 한국과학기술원 Rna oligonucleotide and immune activator comprising same
CA3002744A1 (en) 2015-10-19 2017-04-27 Rxi Pharmaceuticals Corporation Reduced size self-delivering nucleic acid compounds targeting long non-coding rna
JPWO2017068791A1 (en) * 2015-10-23 2018-08-09 レナセラピューティクス株式会社 Nucleic acid complex having at least one bulge structure
EP3368089A4 (en) 2015-10-26 2019-05-29 Translate Bio Ma, Inc. NANOPARTICLE FORMULATIONS FOR ADMINISTRATION OF NUCLEIC ACID COMPLEXES
WO2017079291A1 (en) 2015-11-02 2017-05-11 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating c90rf72
WO2017079227A1 (en) 2015-11-05 2017-05-11 University Of Connecticut Compositions and methods for the treatment of liver fibrosis
CN108348478A (en) 2015-11-06 2018-07-31 Ionis 制药公司 Regulates apolipoprotein(a) expression
IL289849B2 (en) * 2015-11-10 2024-01-01 Nat Inst Biotechnology Negev Ltd Means and methods for reducing the tumorigenicity of cancer stem cells
EP4454637A3 (en) 2015-11-16 2025-01-08 Olix Pharmaceuticals, Inc. Treatment of age-related macular degeneration using rna complexes that target myd88 or tlr3
CN108289906B (en) 2015-11-19 2022-03-11 公立大学法人名古屋市立大学 Antineoplastic Drug Delivery Formulations
JP7008328B2 (en) * 2015-11-20 2022-01-25 国立大学法人九州大学 Immune regulator
BR112018011045A2 (en) * 2015-11-30 2018-11-21 Univ British Columbia monocarboxylate transporter 4 (mct4) antisense (aso) oligonucleotide inhibitors for use as a therapy in cancer treatment
EP3389670A4 (en) 2015-12-04 2020-01-08 Ionis Pharmaceuticals, Inc. Methods of treating breast cancer
WO2017100236A1 (en) 2015-12-07 2017-06-15 Alnylam Pharmaceuticals, Inc. Methods and compositions for treating a serpinc1-associated disorder
CN115433707A (en) 2015-12-07 2022-12-06 再生疗法有限公司 Method for derivatization of different pluripotent stem cell-derived brown adipocytes
WO2017100542A1 (en) * 2015-12-10 2017-06-15 Alnylam Pharmaceuticals, Inc. Sterol regulatory element binding protein (srebp) chaperone (scap) irna compositions and methods of use thereof
ES2844899T3 (en) 2015-12-10 2021-07-23 Fibrogen Inc Methods for treating motor neuron diseases
WO2017106111A1 (en) 2015-12-13 2017-06-22 Nitto Denko Corporation Sirna structures for high activity and reduced off target
EP3181698A1 (en) 2015-12-16 2017-06-21 European Molecular Biology Laboratory (EMBL) Microrna mir-142 as stem cell marker
US20190002887A1 (en) 2015-12-31 2019-01-03 Ionis Pharmaceuticals, Inc. Methods for reducing ataxin-2 expression
WO2017120365A1 (en) 2016-01-05 2017-07-13 Ionis Pharmaceuticals, Inc. Methods for reducing lrrk2 expression
AU2017210726B2 (en) 2016-01-31 2023-08-03 University Of Massachusetts Branched oligonucleotides
JP7003044B2 (en) 2016-02-02 2022-01-20 オリックス ファーマシューティカルズ，インコーポレーテッド Treatment of angiogenesis-related diseases with RNA complexes targeting ANGPT2 and PDGFB
JP6944942B2 (en) * 2016-02-02 2021-10-06 オリックス ファーマシューティカルズ，インコーポレーテッド Treatment of atopic dermatitis and asthma with RNA complexes targeting IL4Rα, TRPA1, or F2RL1
US10519442B2 (en) * 2016-02-11 2019-12-31 City Of Hope Twist signaling inhibitor compositions and methods of using the same
WO2017143156A1 (en) 2016-02-19 2017-08-24 Genisphere Llc Nucleic acid carriers and therapeutic methods of use
US11377659B2 (en) * 2016-02-19 2022-07-05 The Regents Of The University Oe California Short hairpin RNA (shRNA734) and use of same to positively select and eliminate genetically modified cells
AU2017229778A1 (en) 2016-03-09 2018-08-16 Ionis Pharmaceuticals, Inc. Methods and compositions for inhibiting PMP22 expression
CA3013799A1 (en) 2016-03-16 2017-09-21 Ionis Pharmaceuticals, Inc. Methods of modulating keap1
WO2017161168A1 (en) 2016-03-16 2017-09-21 Ionis Pharmaceuticals, Inc. Modulation of dyrk1b expression
CN105925576B (en) * 2016-03-24 2018-04-20 嘉兴市第一医院 SiRNA, ShorthairpinRNA and carrier and application for mammal R Spondin3 gene targets
MA45340A (en) * 2016-04-01 2019-02-06 Avidity Biosciences Llc ANDROGEN RECEPTOR NUCLEIC ACIDS AND THEIR USES
MA45328A (en) 2016-04-01 2019-02-06 Avidity Biosciences Llc NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND USES THEREOF
ES2640524B1 (en) * 2016-04-01 2018-09-24 Universidad Autónoma de Madrid USE OF TCFL5 / CHA AS A NEW MARKER FOR THE PROGNOSIS AND / OR DIFFERENTIAL DIAGNOSIS OF ACUTE LYMPHOBLASTIC LEUKEMIES
US10301628B2 (en) 2016-04-11 2019-05-28 Olix Pharmaceuticals, Inc. Treatment of idiopathic pulmonary fibrosis using RNA complexes that target connective tissue growth factor
NZ747314A (en) * 2016-04-14 2022-07-29 Benitec Ip Holdings Inc Reagents for treatment of oculopharyngeal muscular dystrophy (opmd) and use thereof
EA201892366A1 (en) 2016-04-18 2019-03-29 Сарепта Терапьютикс, Инк. ANTISMINAL OLIGOMERS AND METHODS OF THEIR APPLICATION FOR THE TREATMENT OF DISEASES ASSOCIATED WITH THE GENE OF THE ACID ALPHA-GLUCOSIDASE
CN107345230A (en) * 2016-05-05 2017-11-14 江苏命码生物科技有限公司 A kind of siRNA of suppression K-RAS gene expressions and its precursor and application
CN105969771A (en) * 2016-05-30 2016-09-28 东北师范大学 shRNA targeted to silent FOXG1
US20230348911A1 (en) * 2016-06-08 2023-11-02 Aalborg Universitet Antisense oligonucleotides for modulation of long noncoding rnas
PT109454A (en) * 2016-06-14 2017-12-14 Phyzat Biopharmaceuticals Lda NUCLEIC ACIDS OF INTERFERENCE AND COMPOSITIONS THAT UNDERSTAND THEM
US11198867B2 (en) 2016-06-16 2021-12-14 Ionis Pharmaceuticals, Inc. Combinations for the modulation of SMN expression
MA45496A (en) 2016-06-17 2019-04-24 Hoffmann La Roche NUCLEIC ACID MOLECULES FOR PADD5 OR PAD7 MRNA REDUCTION FOR TREATMENT OF HEPATITIS B INFECTION
WO2017219017A1 (en) 2016-06-17 2017-12-21 Ionis Pharmaceuticals, Inc. Modulation of gys1 expression
KR101916652B1 (en) 2016-06-29 2018-11-08 올릭스 주식회사 Compounds improving RNA interference of small interfering RNA and use thereof
CN107557363B (en) * 2016-06-30 2021-03-12 中国科学院分子细胞科学卓越创新中心 Inducible siRNA expression vector and its preparation and application
WO2018009547A1 (en) * 2016-07-05 2018-01-11 The Usa, As Represented By The Secretary, Dept. Of Health And Human Services Diagnosing col6-related disorders and methods for treating same
US11252965B2 (en) * 2016-07-13 2022-02-22 Indiana University Research And Technology Corporation RNAi insecticide materials and methods
AR109207A1 (en) * 2016-08-05 2018-11-07 Syngenta Participations Ag PATHOPE CONTROL OF COLEOPTERS USING RNA MOLECULES
WO2018031933A2 (en) 2016-08-12 2018-02-15 University Of Massachusetts Conjugated oligonucleotides
UY37376A (en) * 2016-08-26 2018-03-23 Amgen Inc ARNI CONSTRUCTIONS TO INHIBIT EXPRESSION OF ASGR1 AND METHODS FOR USE
WO2018052891A2 (en) * 2016-09-15 2018-03-22 The Brigham And Women's Hospital, Inc. Modulation of pcsk9 and ldlr through drp1 inhibition
JP7132911B2 (en) 2016-09-16 2022-09-07 バイオ－パス ホールディングス， インコーポレイテッド Combination therapy with liposomal antisense oligonucleotides
US10933081B2 (en) 2016-09-21 2021-03-02 Alnylam Pharmaceuticals, Inc. Myostatin iRNA compositions and methods of use thereof
JOP20190065A1 (en) 2016-09-29 2019-03-28 Ionis Pharmaceuticals Inc Compounds and methods for reducing tau expression
US11400161B2 (en) 2016-10-06 2022-08-02 Ionis Pharmaceuticals, Inc. Method of conjugating oligomeric compounds
JP7623784B2 (en) 2016-10-13 2025-01-29 ジュノー セラピューティクス インコーポレイテッド Immunotherapeutic methods and compositions involving tryptophan metabolic pathway modulators - Patents.com
WO2018078648A2 (en) * 2016-10-25 2018-05-03 Council Of Scientific & Industrial Research Gold nanoparticle based formulation for use in cancer therapy
JOP20190104A1 (en) 2016-11-10 2019-05-07 Ionis Pharmaceuticals Inc Compounds and methods for reducing atxn3 expression
US10646540B2 (en) 2016-11-18 2020-05-12 City Of Hope Peptide inhibitors of twist
TW202313978A (en) 2016-11-23 2023-04-01 美商阿尼拉製藥公司 Serpina1 irna compositions and methods of use thereof
CN106421790B (en) * 2016-11-25 2018-12-25 复旦大学附属金山医院 Application of the inhibitor of CMPK in the drug of preparation treatment oophoroma
WO2018102745A1 (en) 2016-12-02 2018-06-07 Cold Spring Harbor Laboratory Modulation of lnc05 expression
KR20190098747A (en) 2016-12-05 2019-08-22 주노 쎄러퓨티크스 인코퍼레이티드 Method of manufacturing engineered cells for adoptive cell therapy
TW201827596A (en) * 2016-12-23 2018-08-01 日商協和醱酵麒麟有限公司 Nucleic acid inhibiting expression of complement factor B
EP3565577A4 (en) 2017-01-06 2020-10-07 Avidity Biosciences, Inc. NUCLEIC ACID-POLYPEPTIDE COMPOSITIONS AND METHODS FOR INDUCING EXON SKIPPING
KR20240096846A (en) 2017-01-10 2024-06-26 애로우헤드 파마슈티컬스 인코포레이티드 Alpha-1 antitrypsin (aat) rnai agents, compositions including aat rnai agents, and methods of use
US11174325B2 (en) 2017-01-12 2021-11-16 Carnegie Mellon University Surfactant assisted formation of a catalyst complex for emulsion atom transfer radical polymerization processes
WO2018130584A1 (en) * 2017-01-13 2018-07-19 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides for modulating nfkb2 expression
EP3580339A4 (en) 2017-02-10 2020-12-23 Research & Business Foundation Sungkyunkwan University LONG DOUBLE STRANDED RNA FOR RNA INTERFERENCE
CN106668863B (en) * 2017-02-21 2019-04-23 南方医科大学 Drug targeting KTN1 for cutaneous squamous cell carcinoma
US20200032270A1 (en) * 2017-03-09 2020-01-30 Kyowa Kirin Co., Ltd. Nucleic acid capable of inhibiting expression of masp2
US11261441B2 (en) 2017-03-29 2022-03-01 Bluebird Bio, Inc. Vectors and compositions for treating hemoglobinopathies
HUE061894T2 (en) * 2017-04-05 2023-08-28 Silence Therapeutics Gmbh Rna interference mediated inhibition of tmprss6
US11324820B2 (en) 2017-04-18 2022-05-10 Alnylam Pharmaceuticals, Inc. Methods for the treatment of subjects having a hepatitis b virus (HBV) infection
CA3058018A1 (en) 2017-04-19 2018-10-25 Bio-Path Holdings, Inc. P-ethoxy nucleic acids for stat3 inhibition
CN110636835A (en) 2017-04-19 2019-12-31 拜奥-帕斯控股股份有限公司 P-ethoxy nucleic acid for BCL2 inhibition
NO344051B1 (en) * 2017-05-04 2019-08-26 Patogen As Novel virus in Fish and Method for detection
EP3618839A4 (en) 2017-05-05 2021-06-09 Voyager Therapeutics, Inc. COMPOSITIONS AND TREATMENT METHODS FOR AMYOTROPHIC LATERAL SCLEROSIS (ALS)
WO2018208972A1 (en) 2017-05-09 2018-11-15 University Of Massachusetts Methods of treating amyotrophic lateral sclerosis (als)
WO2018218135A1 (en) 2017-05-25 2018-11-29 The Children's Medical Center Corporation Bcl11a guide delivery
TW201903149A (en) * 2017-05-31 2019-01-16 日商協和醱酵麒麟有限公司 APCS-expression-suppressing nucleic acids
KR101940061B1 (en) * 2017-06-02 2019-01-21 김준 Composition for Inhibition of Metastasis in Cancer Cells Including Ribosomal Protein S3 siRNAs
CN107177594B (en) * 2017-06-07 2020-03-03 浙江大学 siRNA for specifically inhibiting CA7 gene expression and recombinant vector and application thereof
FR3067933B1 (en) * 2017-06-21 2020-07-17 L'oreal MODULATORS OF OPSIN 3 IN THE MODULATION OF PIGMENTATION OF THE SKIN
EP3642341A4 (en) 2017-06-23 2021-06-16 University Of Massachusetts TWO-DAY SELF-RELEASING SIRNA AND RELATED PROCEDURES
US20200131573A1 (en) * 2017-06-30 2020-04-30 The Trustees Of Princeton University Genetic variants associated with human-directed hyper-social behavior in domestic dogs
PE20200746A1 (en) 2017-07-06 2020-07-24 Arrowhead Pharmaceuticals Inc IARN AGENTS FOR THE INHIBITION OF THE EXPRESSION OF ALFA-ENAC AND METHODS OF USE
WO2019010301A1 (en) * 2017-07-06 2019-01-10 Kapiloff Michael S Treatment of heart disease by inhibition of the action of muscle a-kinase anchoring protein (makap)
CA3069451A1 (en) 2017-07-13 2019-01-17 Alnylam Pharmaceuticals, Inc. Methods for inhibition of hao1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression
EP3655534B1 (en) 2017-07-18 2025-07-16 CSL Behring Gene Therapy, Inc. Compositions and methods for treating beta-hemoglobinopathies
GB201711809D0 (en) 2017-07-21 2017-09-06 Governors Of The Univ Of Alberta Antisense oligonucleotide
CN111201024A (en) * 2017-08-07 2020-05-26 菲奥医药公司 Chemically modified oligonucleotides
CN110020273B (en) * 2017-08-16 2021-06-29 北京京东尚科信息技术有限公司 Method, device and system for generating thermodynamic diagram
WO2019036613A1 (en) 2017-08-18 2019-02-21 Ionis Pharmaceuticals, Inc. Modulation of the notch signaling pathway for treatment of respiratory disorders
EP3678674B1 (en) * 2017-09-06 2025-02-12 Baylor College of Medicine Park2 nucleic acid and/or park2 polypeptide and salvador shrna for use in the treatment of cardiac conditions
WO2019047914A1 (en) * 2017-09-07 2019-03-14 北京泰德制药股份有限公司 Double-stranded rna molecule targeting ckip-1 and use thereof
WO2019051173A1 (en) 2017-09-08 2019-03-14 Ionis Pharmaceuticals, Inc. Modulators of smad7 expression
CA3075205A1 (en) * 2017-09-08 2019-03-14 Mina Therapeutics Limited Stabilized hnf4a sarna compositions and methods of use
MX2020002648A (en) 2017-09-11 2020-07-22 Arrowhead Pharmaceuticals Inc Rnai agents and compositions for inhibiting expression of apolipoprotein c-iii (apoc3).
BR112020003126A2 (en) 2017-09-14 2020-10-13 Arrowhead Pharmaceuticals, Inc. rnai agents and compositions for inhibiting the expression of angiopoietin type 3 (angptl3), and methods of use
AU2018336806B2 (en) 2017-09-19 2025-04-10 Alnylam Pharmaceuticals, Inc. Compositions and methods for treating transthyretin (TTR) mediated amyloidosis
EP3684937A4 (en) 2017-09-22 2021-06-02 University of Massachusetts Sod1 dual expression vectors and uses thereof
EP3688160A2 (en) * 2017-09-28 2020-08-05 Secarna Pharmaceuticals GmbH & Co. KG Oligonucleotide inhibiting the expression of chop
EP3672579A4 (en) * 2017-10-10 2021-06-23 University of Virginia Patent Foundation Compositions and methods for treating age-related macular degeneration and geographic atrophy
MA52151A (en) 2017-10-16 2020-05-06 Hoffmann La Roche NUCLEIC ACID MOLECULE FOR PAPD5 AND PAPD7 mRNA REDUCTION FOR TREATMENT OF HEPATITIS B INFECTION
CN111479924B (en) 2017-10-16 2024-06-14 沃雅戈治疗公司 Treatment of Amyotrophic Lateral Sclerosis (ALS)
CA3078960A1 (en) 2017-10-20 2019-04-25 Dicerna Pharmaceuticals, Inc. Methods for treating hepatitis b infection
SG11202003862PA (en) * 2017-11-01 2020-05-28 Editas Medicine Inc Methods, compositions and components for crispr-cas9 editing of tgfbr2 in t cells for immunotherapy
US11866701B2 (en) 2017-11-01 2024-01-09 Alnylam Pharmaceuticals, Inc. Complement component C3 iRNA compositions and methods of use thereof
WO2019094315A1 (en) * 2017-11-08 2019-05-16 Aptamer Diagnostic, Inc. D-dimer-specific aptamers and methods of use in diagnostics, therapeutic and theranostic purposes
TWI809004B (en) 2017-11-09 2023-07-21 美商Ionis製藥公司 Compounds and methods for reducing snca expression
GB201718701D0 (en) * 2017-11-13 2017-12-27 Syngenta Participations Ag Improvements in or relating to gene silencing
CN109777800A (en) * 2017-11-15 2019-05-21 信雅生物科技（苏州）有限公司 It is a kind of be capable of specificity inhibit ZBED1 gene siRNA construction method and its application
WO2019100039A1 (en) * 2017-11-20 2019-05-23 Alnylam Pharmaceuticals, Inc. Serum amyloid p component (apcs) irna compositions and methods of use thereof
GB201719680D0 (en) * 2017-11-27 2018-01-10 Devgen Nv Improvements in or relating to gene silencing
AU2018374219C1 (en) 2017-12-01 2023-05-11 Suzhou Ribo Life Science Co., Ltd. Double-stranded oligonucleotide, composition and conjugate comprising double-stranded oligonucleotide, preparation method therefor and use thereof
WO2019105435A1 (en) 2017-12-01 2019-06-06 苏州瑞博生物技术有限公司 Nucleic acid, composition and conjugate containing nucleic acid, preparation method and use
CN118291456A (en) 2017-12-01 2024-07-05 苏州瑞博生物技术股份有限公司 Nucleic acid, composition containing nucleic acid, conjugate, preparation method and application
EP3719125B1 (en) 2017-12-01 2025-01-08 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate containing same, and preparation method and use
US11414661B2 (en) * 2017-12-01 2022-08-16 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, composition and conjugate containing nucleic acid, preparation method therefor and use thereof
CA3083526A1 (en) 2017-12-06 2019-06-13 Andrew John Geall Compositions and methods of treating muscle atrophy and myotonic dystrophy
JP2021505175A (en) * 2017-12-11 2021-02-18 ロシュ イノベーション センター コペンハーゲン エーエス Oligonucleotides for regulating the expression of FNDC3B
WO2019126641A2 (en) 2017-12-21 2019-06-27 Ionis Pharmaceuticals, Inc. Modulation of frataxin expression
AU2018394875B2 (en) 2017-12-29 2023-08-03 Suzhou Ribo Life Science Co., Ltd. Conjugates and preparation and use thereof
US11713446B2 (en) 2018-01-08 2023-08-01 Iovance Biotherapeutics, Inc. Processes for generating TIL products enriched for tumor antigen-specific T-cells
WO2019136459A1 (en) 2018-01-08 2019-07-11 Iovance Biotherapeutics, Inc. Processes for generating til products enriched for tumor antigen-specific t-cells
EP3737743A1 (en) 2018-01-08 2020-11-18 Iovance Biotherapeutics, Inc. Processes for generating til products enriched for tumor antigen-specific t-cells
GB201800370D0 (en) * 2018-01-10 2018-02-21 Ucl Business Plc Anionic nanocomplexes for nucleic acid delivery
CN108387621B (en) * 2018-01-10 2019-11-26 暨南大学 Cadmium ion aptamer and screen printing electrode electrochemica biological sensor
BR112020014425A2 (en) 2018-01-15 2020-12-29 Ionis Pharmaceuticals, Inc. DNM2 EXPRESSION MODULATORS
JP2021511042A (en) * 2018-01-16 2021-05-06 ディセルナ ファーマシューティカルズ インコーポレイテッド Compositions and Methods for Inhibiting ALDH2 Expression
WO2019155387A1 (en) * 2018-02-07 2019-08-15 St. Jude Children's Research Hospital Epigenetic histone regulation mediated by cxorf67
AU2019219194A1 (en) 2018-02-09 2020-08-06 Genentech, Inc. Oligonucleotides for modulating TMEM106B expression
US11732260B2 (en) 2018-03-02 2023-08-22 Ionis Pharmaceuticals, Inc. Compounds and methods for the modulation of amyloid-β precursor protein
WO2019168687A1 (en) * 2018-03-02 2019-09-06 Dicerna Pharmaceuticals, Inc. Compositions and methods for inhibiting gys2 expression
TWI840345B (en) 2018-03-02 2024-05-01 美商Ionis製藥公司 Modulators of irf4 expression
JP7558563B2 (en) 2018-03-15 2024-10-01 ケーエスキュー セラピューティクス， インコーポレイテッド Gene Regulatory Compositions and Methods for Improved Immunotherapy - Patent application
CA3091146A1 (en) * 2018-03-21 2019-09-26 Regeneron Pharmaceuticals, Inc. 17.beta.-hydroxysteroid dehydrogenase type 13 (hsd17b13) irna compositions and methods of use thereof
US11661601B2 (en) 2018-03-22 2023-05-30 Ionis Pharmaceuticals, Inc. Methods for modulating FMR1 expression
IL314908A (en) * 2018-03-29 2024-10-01 Technion Res & Dev Foundation Bubbles containing PTEN inhibitor and their uses
JP7275164B2 (en) 2018-04-11 2023-05-17 アイオーニス ファーマシューティカルズ， インコーポレーテッド Regulators of EZH2 expression
US12350284B2 (en) 2018-05-02 2025-07-08 The Children's Medical Center Corporation BCL11A microRNAs for treating hemoglobinopathies
AR115375A1 (en) 2018-05-09 2021-01-13 Ionis Pharmaceuticals Inc COMPOUNDS AND METHODS TO REDUCE THE EXPRESSION OF ATXN3
CU20200082A7 (en) 2018-05-09 2021-06-08 Ionis Pharmaceuticals Inc COMPOUNDS AND METHODS FOR REDUCING THE EXPRESSION OF FXI
EP3807411A4 (en) 2018-06-14 2022-08-03 Ionis Pharmaceuticals, Inc. Compounds and methods for increasing stmn2 expression
NO344698B1 (en) * 2018-06-15 2020-03-09 Patogen As Novel fish virus
CA3103756A1 (en) 2018-06-22 2019-12-26 F. Hoffman-La Roche Ag Oligonucleotides for modulating scn9a expression
TWI833770B (en) 2018-06-27 2024-03-01 美商Ionis製藥公司 Compounds and methods for reducing lrrk2 expression
BR112020026973A2 (en) 2018-07-03 2021-04-06 F. Hoffmann-La Roche Ag OLIGONUCLEOTIDS FOR MODULATION OF TAU EXPRESSION
WO2020011653A1 (en) * 2018-07-09 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting kynu
WO2020011744A2 (en) * 2018-07-11 2020-01-16 Roche Innovation Center Copenhagen A/S Antisense oligonucleotides targeting cers5
AR115847A1 (en) 2018-07-25 2021-03-03 Ionis Pharmaceuticals Inc COMPOUNDS AND METHODS TO REDUCE THE EXPRESSION OF ATXN2
EP3598995A1 (en) * 2018-07-26 2020-01-29 Silence Therapeutics GmbH Products and compositions
EP3830259A4 (en) 2018-08-02 2022-05-04 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating facioscapulohumeral muscular dystrophy
US11827882B2 (en) 2018-08-10 2023-11-28 University Of Massachusetts Modified oligonucleotides targeting SNPs
JP7625512B2 (en) 2018-08-13 2025-02-03 アルナイラム ファーマシューティカルズ， インコーポレイテッド Hepatitis B virus (HBV) dsRNA agent compositions and methods of use thereof
US12295930B2 (en) * 2018-08-14 2025-05-13 Emory University Inducing proliferation of cardiomyocytes and therapeutic uses related thereto
EP3842534A4 (en) 2018-08-21 2022-07-06 Suzhou Ribo Life Science Co., Ltd. NUCLEIC ACID, PHARMACEUTICAL COMPOSITION AND CONJUGATE WITH NUCLEIC ACID AND THEIR USE
EP3840759A4 (en) 2018-08-23 2022-06-01 University Of Massachusetts FULLY STABILIZED O-METHYL RICH OLIGONUCLEOTIDES
CN109085365B (en) * 2018-08-27 2020-06-23 山东农业大学 Blocking agent for inhibiting highly pathogenic porcine reproductive and respiratory syndrome virus infection
WO2020046985A1 (en) * 2018-08-27 2020-03-05 North Carolina State University Targeting kit with splice switching oligonucleotides to induce apoptosis of mast cells
EP3843791A4 (en) * 2018-08-31 2023-08-02 University of Florida Research Foundation, Incorporated Adeno-associated viral vectors for the treatment of best disease
US20220280545A1 (en) * 2018-09-10 2022-09-08 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating cln3 expression
US11896674B2 (en) 2018-09-30 2024-02-13 Suzhou Ribo Life Science Co., Ltd. SiRNA conjugate, preparation method therefor and use thereof
JP7191301B2 (en) * 2018-10-02 2022-12-19 小胞体ストレス研究所株式会社 Growth inhibitor for cancer cells with poor prognosis
BR112021008069A2 (en) * 2018-11-02 2021-11-03 Biomarin Tech Bv Bispecific antisense oligonucleotides for dystrophin exon skipping
TW202028222A (en) 2018-11-14 2020-08-01 美商Ionis製藥公司 Modulators of foxp3 expression
KR20210092761A (en) 2018-11-15 2021-07-26 아이오니스 파마수티컬즈, 인코포레이티드 IRF5 expression regulator
US12281305B2 (en) 2018-11-21 2025-04-22 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing prion expression
EP3884051A2 (en) 2018-11-23 2021-09-29 Sanofi Novel rna compositions and methods for inhibiting angptl8
CN111228289A (en) * 2018-11-28 2020-06-05 中国科学院大连化学物理研究所 Application of PLIN2 inhibitor and medicine mixture for treating tumor
ES2766855A1 (en) * 2018-12-14 2020-06-15 Consejo Superior Investigacion Rhoq as a pharmaceutical target for neurological disorders (Machine-translation by Google Translate, not legally binding)
ES2766950A1 (en) * 2018-12-14 2020-06-15 Consejo Superior Investigacion ARHGEF6 as a pharmaceutical target for neurological disorders (Machine-translation by Google Translate, not legally binding)
CR20210387A (en) 2018-12-20 2021-08-19 Amgen Inc Kif18a inhibitors
IL319265A (en) 2018-12-21 2025-04-01 Avidity Biosciences Inc Anti-transferrin receptor antibodies and uses thereof
US11452738B2 (en) * 2019-01-04 2022-09-27 Empirico Inc. Treatment of thymic stromal lymphopoietin (TSLP) related diseases by inhibition of long-form TSLP transcripts
WO2020146521A2 (en) 2019-01-09 2020-07-16 Arrowhead Pharmaceuticals, Inc. Rnai agents for inhibiting expression of hif-2 alpha (epas1), compositions thereof, and methods of use
WO2020144295A1 (en) 2019-01-10 2020-07-16 Biontech Rna Pharmaceuticals Gmbh Localized administration of rna molecules for therapy
CN113454223B (en) * 2019-01-15 2024-09-13 柏业公司 DKK1 gene-targeted double-stranded oligonucleotide, construct comprising same, and hair loss prevention or hair growth composition comprising same
AU2020207935A1 (en) 2019-01-18 2021-08-26 University Of Massachusetts Dynamic pharmacokinetic-modifying anchors
WO2020160453A1 (en) 2019-01-31 2020-08-06 Ionis Pharmaceuticals, Inc. Modulators of yap1 expression
EP3931328A4 (en) 2019-02-27 2023-09-13 Ionis Pharmaceuticals, Inc. MODULATORS OF MALAT1 EXPRESSION
WO2020180645A1 (en) * 2019-03-01 2020-09-10 Meso Scale Technologies, Llc. Electrochemiluminescent labeled probes for use in immunoassay methods, methods using such and kits comprising same
AU2020239987A1 (en) * 2019-03-15 2021-11-04 University Of Massachusetts Oligonucleotides for tissue specific ApoE modulation
WO2020190739A1 (en) * 2019-03-15 2020-09-24 University Of Washington Improved survival of human cells differentiated in vitro by prpf31 gene expression knockdown
JP7550165B2 (en) 2019-03-29 2024-09-12 アイオーニス ファーマシューティカルズ， インコーポレーテッド Compounds and methods for modulating UBE3A-ATS
AU2020259449A1 (en) 2019-04-17 2021-12-09 Aadigen, Llc Peptides and nanoparticles for intracellular delivery of molecules
EP3956448A4 (en) * 2019-04-18 2022-10-19 University of Massachusetts AIM2 INHIBITORS AND THEIR USES
CN111849968A (en) * 2019-04-30 2020-10-30 中美瑞康核酸技术(南通)研究院有限公司 Oligonucleotide molecule and application thereof in acute intermittent porphyria treatment
WO2020225813A1 (en) 2019-05-05 2020-11-12 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Restoration of the cftr function by splicing modulation
AU2020276156A1 (en) 2019-05-15 2021-12-16 The Board Of Trustees Of The Leland Stanford Junior University Treatment of heart disease by disruption of the anchoring of PP2A
EP3974532A4 (en) * 2019-05-22 2024-01-24 Suzhou Ribo Life Science Co., Ltd. Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use
US20200369759A1 (en) 2019-05-23 2020-11-26 Fibrogen, Inc. Methods of treatment of muscular dystrophies
JP7614650B2 (en) * 2019-05-24 2025-01-16 スーチョウ リボ ライフ サイエンス カンパニー、リミテッド Nucleic acids, drug compositions and complexes and methods of preparation and use
JP2022535717A (en) * 2019-05-24 2022-08-10 エンピリコ インク． Treatment of Angiopoietin-Like 7 (ANGPTL7) Related Diseases
WO2020238766A1 (en) * 2019-05-24 2020-12-03 苏州瑞博生物技术股份有限公司 Nucleic acid, pharmaceutical composition, conjugate, preparation method, and use
US20220251567A1 (en) * 2019-07-10 2022-08-11 Inserm (Institut National De La Santè Et De La Recherche Médicale) Methods for the treatment of epilepsy
EP3956450B1 (en) 2019-07-26 2025-08-13 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating gfap
US20220267778A1 (en) 2019-07-30 2022-08-25 Shionogi & Co., Ltd. Nucleic acid drug targeting murf1
KR20220047989A (en) 2019-08-09 2022-04-19 유니버시티 오브 매사추세츠 Chemically modified oligonucleotides targeting SNPs
AU2020329191A1 (en) 2019-08-12 2022-03-31 Regeneron Pharmaceuticals, Inc. Macrophage stimulating 1 receptor (MST1R) variants and uses thereof
US20220280543A1 (en) * 2019-08-23 2022-09-08 University Of Virginia Patent Foundation Ddx17 and nlrc4 targeting for inflammatory diseases
US12195772B2 (en) 2019-08-30 2025-01-14 Inari Agriculture Technology, Inc. RNA-guided nucleases and DNA binding proteins
JP7675027B2 (en) * 2019-08-30 2025-05-12 エージェンシー フォー サイエンス，テクノロジー アンド リサーチ Methods for promoting survival and/or function of motor neurons, and related agents, uses, and methods
EP3791930A1 (en) * 2019-09-13 2021-03-17 Secarna Pharmaceuticals GmbH & Co. KG Inhibitor of metadherin expression
US12365894B2 (en) 2019-09-16 2025-07-22 University Of Massachusetts Branched lipid conjugates of siRNA for specific tissue delivery
KR102100163B1 (en) 2019-09-24 2020-04-13 테고사이언스 (주) Compositions of Prevention or Treatment of Keloid or Hypertrophic scar
JP2022551970A (en) * 2019-10-16 2022-12-14 ブラウン ユニバーシティ muscle regeneration and growth
BR112022007540A2 (en) 2019-10-22 2022-07-12 Alnylam Pharmaceuticals Inc COMPONENTS COMPLEMENTARY C3 IRNA COMPOSITIONS AND METHODS OF USE THEREOF
TW202130809A (en) * 2019-10-29 2021-08-16 美商愛羅海德製藥公司 Rnai agents for inhibiting expression of beta-enac, compositions thereof, and methods of use
EP4051796A1 (en) * 2019-11-01 2022-09-07 Alnylam Pharmaceuticals, Inc. Compositions and methods for silencing dnajb1-prkaca fusion gene expression
EP4054655A4 (en) * 2019-11-08 2024-02-28 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing spdef expression
WO2021092459A1 (en) * 2019-11-08 2021-05-14 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing spdef expression
CN110859960B (en) * 2019-11-26 2022-03-04 深圳先进技术研究院 Application of combination of AMPK-targeted inhibitor/siRNA and proteasome inhibitor in preparation of antitumor drugs
KR20220112290A (en) * 2019-12-09 2022-08-10 엠피리코 인크. Oligonucleotides for the treatment of angiopoietin-like 4 (ANGPTL4) related diseases
US20210214727A1 (en) * 2019-12-20 2021-07-15 Hoffmann-La Roche Inc. Enhanced oligonucleotides for inhibiting scn9a expression
PE20230430A1 (en) * 2019-12-23 2023-03-08 Versameb Ag COMPOSITIONS AND METHODS TO SIMULTANEOUSLY MODULATE GENE EXPRESSION
AU2020415455A1 (en) * 2019-12-23 2022-07-14 University Of Massachusetts Oligonucleotides for tissue specific gene expression modulation
KR20210086503A (en) * 2019-12-31 2021-07-08 한국원자력연구원 Composition comprising wdr34 inhibitor for inhibiting growth of cancer stem cells and uses thereof
US20230073368A1 (en) 2020-02-11 2023-03-09 Turun Yliopisto Therapy of ras-dependent cancers
CN115087451A (en) * 2020-02-21 2022-09-20 里普利科股份有限公司 Methods and compositions for inhibiting hepatitis B and hepatitis D virus infection
WO2021173984A2 (en) * 2020-02-28 2021-09-02 University Of Massachusetts Oligonucleotides for prnp modulation
EP4051292A4 (en) 2020-02-28 2023-12-06 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR MODULATING SMN2
US20230124616A1 (en) * 2020-03-06 2023-04-20 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating kcnq2
CN115485383A (en) * 2020-03-06 2022-12-16 阿尔尼拉姆医药品有限公司 Ketohexokinase (KHK) iRNA compositions and methods of use thereof
CN115666589A (en) 2020-03-19 2023-01-31 艾维迪提生物科学公司 Compositions and methods for treating facioscapulohumeral muscular dystrophy
US20230126881A1 (en) * 2020-03-27 2023-04-27 Alnylam Pharmaceuticals, Inc. Fc FRAGMENT OF IgG RECEPTOR AND TRANSPORTER (FCGRT) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
CA3177180A1 (en) 2020-03-27 2021-09-30 Avidity Biosciences, Inc. Compositions and methods of treating muscle dystrophy
CN113444723A (en) * 2020-03-27 2021-09-28 北京键凯科技股份有限公司 Interfering RNA for inhibiting vascular endothelial growth factor receptor 2 gene expression and application thereof
CN115667551A (en) * 2020-04-14 2023-01-31 美国安进公司 KIF18A inhibitors for the treatment of neoplastic diseases
AU2021264010A1 (en) 2020-05-01 2022-12-08 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating ATXN1
JP2023525799A (en) * 2020-05-11 2023-06-19 ストーク セラピューティクス，インク． OPA1 antisense oligomers for treatment of conditions and diseases
WO2021229036A1 (en) * 2020-05-13 2021-11-18 F. Hoffmann-La Roche Ag Oligonucleotide agonists targeting progranulin
EP4150093A4 (en) 2020-05-14 2024-06-19 Ariz Precision Medicine, Inc. Cancer treatment using sirna to modulate expression of prdm2/riz protein
CN111714510B (en) * 2020-05-18 2021-07-06 北京航空航天大学 Application of long non-coding RNA SNHG12 inhibitors in the preparation of anti-osteoporosis drugs
WO2021252523A2 (en) * 2020-06-09 2021-12-16 Alnylam Pharmaceuticals, Inc. TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6 (TRAF6) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
EP4165185A4 (en) * 2020-06-11 2025-09-10 Genetic Intelligence Inc New York Ny COMPOSITIONS FOR FN GENE MODULATION AND METHODS THEREFOR
US11459567B2 (en) 2020-06-24 2022-10-04 Patricia Virginia Elizalde Specific siRNA molecules, composition and use thereof for the treatment of triple negative breast cancer
KR20230029837A (en) 2020-06-29 2023-03-03 아이오니스 파마수티컬즈, 인코포레이티드 Compounds and methods for modulating PLP1
CA3186853A1 (en) * 2020-07-23 2022-01-27 John Mansell Compositions and methods for treating pain and anxiety disorders
EP4189090A4 (en) 2020-07-28 2025-02-26 Ionis Pharmaceuticals, Inc. COMPOUNDS AND METHODS FOR REDUCING APP EXPRESSION
WO2022031591A2 (en) * 2020-08-03 2022-02-10 University Of Massachusetts Oligonucleotides for htt-1a modulation
EP4192478A2 (en) * 2020-08-04 2023-06-14 Dicerna Pharmaceuticals, Inc. Compositions and methods for inhibiting plp1 expression
PE20231567A1 (en) 2020-08-07 2023-10-04 Ionis Pharmaceuticals Inc COMPOUNDS AND METHODS TO MODULATE SCN2A
WO2022036140A2 (en) * 2020-08-13 2022-02-17 Nevada Research & Innovation Corporation Klf11 sirna for treatment of diabetes and obesity
AU2021342155A1 (en) * 2020-09-11 2023-04-13 Arrowhead Pharmaceuticals, Inc. RNAi agents for inhibiting expression of DUX4, compositions thereof, and methods of use
EP4214319A2 (en) 2020-09-17 2023-07-26 Q-State Biosciences, Inc. Therapeutic compositions for treating pain via multiple targets
WO2022071367A1 (en) * 2020-09-30 2022-04-07 富士フイルム株式会社 Double-stranded rna that inhibits production of hepatitis b virus protein, and pharmaceutical composition
WO2022089486A1 (en) * 2020-10-28 2022-05-05 江苏柯菲平医药股份有限公司 Sirna for inhibiting pcsk9 gene expression and modifier thereof and use thereof
WO2022103999A1 (en) 2020-11-13 2022-05-19 Alnylam Pharmaceuticals, Inc. COAGULATION FACTOR V (F5) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
JP2023549505A (en) * 2020-11-13 2023-11-27 ザ ジョージ ワシントン ユニバーシティ， ア コングレッショナリー チャータード ノット－フォー－プロフィット コーポレイション B-spectrin (SPTBN1) deficiency protects mice from high-fat diet-induced liver disease and cancer progression
WO2022109139A1 (en) 2020-11-18 2022-05-27 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating angiotensinogen expression
EP4257686A1 (en) * 2020-12-07 2023-10-11 OliX Pharmaceuticals, Inc. Nucleic acid molecule for induction of asymmetric rnai for inhibiting expression of ror-beta
WO2022133278A2 (en) 2020-12-18 2022-06-23 Ionis Pharmaceuticals, Inc. Compounds and methods for modulating factor xii
EP4288542A4 (en) * 2021-02-08 2025-08-20 Ractigen Therapeutics Multivalent oligonucleotide agent and method of using the same
IL305414A (en) 2021-03-04 2023-10-01 Alnylam Pharmaceuticals Inc Angiopoietin-like 3 (ANGPTL3) IRNA compositions and methods of using them
WO2022197953A2 (en) * 2021-03-17 2022-09-22 Sirnaomics, Inc. Methods of cancer treatment by delivery of sirnas against nsd3
WO2022204440A1 (en) * 2021-03-26 2022-09-29 Alnylam Pharmaceuticals, Inc. ELONGATION OF VERY LONG CHAIN FATTY ACIDS PROTEIN 1 (ELOVL1) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF
US20220348918A1 (en) * 2021-03-29 2022-11-03 University Of Massachusetts Oligonucleotides for syngr-3 modulation
BR112023020626A2 (en) * 2021-04-08 2023-12-19 Arrowhead Pharmaceuticals Inc RNAI AGENTS FOR INHIBITING RECEPTOR EXPRESSION FOR ADVANCED GLYCATION END PRODUCTS, COMPOSITIONS THEREOF AND METHODS OF USE
CN117561067A (en) * 2021-04-16 2024-02-13 费城儿童医院 Compositions and methods for treating H-ABC leukodystrophy
WO2022223515A2 (en) 2021-04-19 2022-10-27 Novo Nordisk A/S Compositions and methods for inhibiting nuclear receptor subfamily 1 group h member 3 (nr1h3) expression
KR20240032184A (en) * 2021-04-22 2024-03-11 몰레큘라 악시옴, 엘엘씨 Compositions and methods for regulating SOS gene expression
KR20240001207A (en) 2021-04-26 2024-01-03 알닐람 파마슈티칼스 인코포레이티드 Transmembrane protease, serine 6 (TMPRSS6) iRNA compositions and methods of using the same
PE20250265A1 (en) * 2021-05-28 2025-01-29 Arrowhead Pharmaceuticals Inc RNAI agents for inhibiting mucin 5AC (MUC5AC) expression, their compositions, and methods of use
IL308418A (en) * 2021-05-28 2024-01-01 Novo Nordisk As Compositions and methods for inhibiting mitochondria amidoxime reducing component 1 (marc1) expression
EP4352086A4 (en) * 2021-06-03 2025-09-17 Univ Chicago Methods and compositions for treating fibrosis
WO2022266042A1 (en) * 2021-06-16 2022-12-22 Empirico Inc. Treatment of mst1r related diseases and disorders
AU2022293556A1 (en) 2021-06-18 2024-01-18 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing ifnar1 expression
JP2024523458A (en) * 2021-06-21 2024-06-28 上海君▲実▼生物医▲薬▼科技股▲分▼有限公司 siRNA inhibiting expression of ANGPTL3 gene and use thereof
US11549112B1 (en) 2021-06-21 2023-01-10 Arrowhead Pharmaceuticals, Inc. RNAi agents for inhibiting expression of xanthine dehydrogenase (XDH), pharmaceutical compositions thereof, and methods of use
CN113416776B (en) * 2021-06-21 2022-04-01 深圳市儿童医院 Biomarker for detecting ventricular septal defect and application thereof
AR126207A1 (en) 2021-06-23 2023-09-27 Univ Massachusetts ANTI-FLT1 OLIGONUCLEOTIDE COMPOUNDS OPTIMIZED FOR THE TREATMENT OF PRE-ECLAMPIA AND OTHER ANGIOGENIC DISORDERS
WO2022269016A1 (en) * 2021-06-25 2022-12-29 Stichting Radboud Universitair Medisch Centrum Allele-specific silencing therapy for dfna21 using antisense oligonucleotides
US11638761B2 (en) 2021-07-09 2023-05-02 Dyne Therapeutics, Inc. Muscle targeting complexes and uses thereof for treating Facioscapulohumeral muscular dystrophy
IL310180A (en) 2021-07-17 2024-03-01 Sirnaomics Inc Products and compositions
KR20240042004A (en) 2021-08-03 2024-04-01 알닐람 파마슈티칼스 인코포레이티드 Transthyretin (TTR) iRNA compositions and methods of using the same
TW202334413A (en) * 2021-08-13 2023-09-01 美商艾拉倫製藥股份有限公司 Factor xii (f12) irna compositions and methods of use thereof
WO2023028564A1 (en) 2021-08-26 2023-03-02 Volastra Therapeutics, Inc. Spiro indoline inhibitors of kif18a
US20250034567A1 (en) * 2021-08-31 2025-01-30 Alnylam Pharmaceuticals, Inc. Cell death-inducing dffa-like effector b (cideb) irna compositions and methods of use thereof
WO2023034870A2 (en) 2021-09-01 2023-03-09 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing dmpk expression
US12043832B2 (en) * 2021-09-16 2024-07-23 Washington University Methods and compositions for reducing pathogenic isoforms
WO2023043953A1 (en) 2021-09-16 2023-03-23 Avidity Biosciences, Inc. Compositions and methods of treating facioscapulohumeral muscular dystrophy
MX2024004011A (en) 2021-10-01 2024-07-01 Adarx Pharmaceuticals Inc PREKALLIKREIN MODULATING COMPOSITIONS AND METHODS OF USING THEM.
JP2024541989A (en) 2021-10-29 2024-11-13 アルナイラム ファーマシューティカルズ， インコーポレイテッド Complement factor B (CFB) iRNA compositions and methods of use thereof
WO2023076450A2 (en) * 2021-10-29 2023-05-04 Alnylam Pharmaceuticals, Inc. HUNTINGTIN (HTT) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF
US20230167447A1 (en) * 2021-11-30 2023-06-01 Genetic Intelligence, Inc Compositions for FNIP1/FNIP2 Gene Modulation and Methods Thereof
WO2023108020A2 (en) * 2021-12-07 2023-06-15 Alnylam Pharmaceuticals, Inc. iRNA COMPOSITIONS AND METHODS FOR SILENCING MYLIP
WO2023122805A1 (en) 2021-12-20 2023-06-29 Vestaron Corporation Sorbitol driven selection pressure method
JP2025500409A (en) 2021-12-22 2025-01-09 キャンプ４ セラピューティクス コーポレイション Methods for modulating gene transcription using antisense oligonucleotides targeted to regulatory RNAs - Patents.com
US20250075209A1 (en) * 2021-12-27 2025-03-06 Apellis Pharmaceuticals, Inc. Rnas for complement inhibition
EP4473477A2 (en) * 2022-02-01 2024-12-11 4D Path Inc. Systems and methods for image-based disease characterization
EP4493570A2 (en) 2022-03-16 2025-01-22 Empirico Inc. Galnac compositions for improving sirna bioavailability
AU2023245603A1 (en) 2022-03-28 2024-11-07 Empirico Inc. Modified oligonucleotides
US12071621B2 (en) 2022-04-05 2024-08-27 Avidity Biosciences, Inc. Anti-transferrin receptor antibody-PMO conjugates for inducing DMD exon 44 skipping
WO2023220566A1 (en) * 2022-05-09 2023-11-16 The Regents Of The University Of California Crispr-cas effector polypeptides and methods of use thereof
WO2023220087A1 (en) * 2022-05-10 2023-11-16 Amylyx Pharmaceuticals, Inc. Oligonucleotide compositions and methods thereof
CN119768519A (en) * 2022-06-24 2025-04-04 伊莱利利公司 ATXN2 RNA interference reagent
CN119677851A (en) * 2022-07-25 2025-03-21 安进公司 RNAi constructs and methods for inhibiting FAM13A expression
CN116042822A (en) * 2022-09-16 2023-05-02 湖南灵康医疗科技有限公司 Application of ZNF32 to regulation of expression of CCND1 gene in resisting colorectal cancer chemotherapy drug resistance
WO2024064858A2 (en) 2022-09-23 2024-03-28 Ionis Pharmaceuticals, Inc. Compounds and methods for reducing mecp2 expression
CN116004543B (en) * 2022-09-26 2025-03-11 南通大学 Application of TRAF6 inhibitor in preparation of medicines for treating human malignant melanoma
CN115844919B (en) * 2022-09-28 2025-09-09 李永 Double-nucleic acid sequence for inhibiting melanoma growth and application thereof
WO2024076934A2 (en) * 2022-10-03 2024-04-11 Cystic Fibrosis Foundation Compositions and methods for modulation of cftr
WO2024104663A1 (en) 2022-11-16 2024-05-23 Unilever Ip Holdings B.V. Method of reducing malodour
WO2024123799A1 (en) * 2022-12-07 2024-06-13 The Regents Of The University Of California Inhibitory nucleic acids and methods of use thereof
KR20250135915A (en) 2022-12-15 2025-09-15 엠피리코 인크. Treatment of MST1-associated diseases and disorders
CN120435558A (en) * 2022-12-29 2025-08-05 沃雅戈治疗公司 Compositions and methods for modulating MAPT
WO2024159113A1 (en) * 2023-01-27 2024-08-02 The Methodist Hospital Modulators of alternative polyadenylation and methods of use thereof
WO2024175586A2 (en) * 2023-02-21 2024-08-29 Vib Vzw Inhibitors of synaptogyrin-3 expression
WO2024187102A2 (en) * 2023-03-09 2024-09-12 Leal Therapeutics, Inc. Compositions and methods for modulating c3
WO2024194491A1 (en) * 2023-03-22 2024-09-26 Ospedale San Raffaele S.R.L. Gene therapy
WO2024215825A1 (en) * 2023-04-14 2024-10-17 Avicenna Biotech Research, Llc Rna-based compositions and methods for treating breast cancer
WO2024229517A1 (en) * 2023-05-05 2024-11-14 Children's Medical Research Institute Methods of treating alt-dependent cancers
WO2024233966A2 (en) * 2023-05-10 2024-11-14 The General Hospital Corporation Modulating stromal and immune cells in atrial disease
WO2024245930A2 (en) * 2023-05-26 2024-12-05 E-Therapeutics Plc Inhibitors of expression and/or function
CN118272371A (en) * 2023-05-30 2024-07-02 北京大学 Short antisense oligonucleotide targeting PLIN2 gene and application thereof
WO2024259134A1 (en) 2023-06-13 2024-12-19 Arnatar Therapeutics, Inc Advanced rna targeting (arnatar) for angiotensinogen
CN116794325B (en) * 2023-06-15 2024-05-10 中山大学 Use of agents for knocking down or inhibiting SLC35F6 in the preparation of drugs for activating AMPK
WO2025007063A1 (en) 2023-06-30 2025-01-02 Avidity Biosciences, Inc. Compositions and methods of using pln-targeting antibody-oligonucleotide conjugates
CN116898975A (en) * 2023-08-21 2023-10-20 中国福利会国际和平妇幼保健院 Application of YTHDC1 inhibitor in preparation of medicines for preventing and treating premature labor
WO2025072748A2 (en) * 2023-09-29 2025-04-03 Insitro, Inc. Compositions and methods for treating nonalcoholic fatty liver disease
CN117070583B (en) * 2023-10-16 2024-05-14 吉林凯莱英制药有限公司 Preparation method of siRNA for inhibiting PCSK9 gene expression
WO2025101484A1 (en) 2023-11-06 2025-05-15 Iovance Biotherapeutics, Inc. Treatment of endometrial cancers with tumor infiltrating lymphocyte therapies
WO2025107242A1 (en) * 2023-11-23 2025-05-30 成都福实生物科技有限公司 Use of mechanical force-responsive macrophage subgroup in diagnostic or prognostic estimation for pancreatic cancer
CN117959445B (en) * 2024-02-04 2025-06-27 北京大学 Use of RNA binding protein inhibitors for the preparation of a medicament for inhibiting replication of chronic hepatitis B virus
EP4603586A1 (en) * 2024-02-16 2025-08-20 Universität zu Lübeck Inhibitory oligonucleotides against adamts7
CN118624918B (en) * 2024-08-08 2024-11-15 中国医学科学院医药生物技术研究所 Application of host cell CXCR6 gene as an anti-flavivirus target in the preparation of anti-flavivirus drugs
CN119799905B (en) * 2025-03-14 2025-06-17 浙江省肿瘤医院 Early prediction markers for papillary thyroid cancer, uses and screening methods thereof
CN120290720A (en) * 2025-04-11 2025-07-11 新疆医科大学第三附属医院 siRNA targeting RPS4X gene, LAMB3-PI3K-AKT signaling pathway inhibitor, ovarian cancer drugs and applications
CN120514724A (en) * 2025-07-24 2025-08-22 济南瑞隆安生物技术有限公司 Application of siRNA in postprandial hyperglycemia treatment preparation

Citations (92)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US647526A (en) * 1899-06-26 1900-04-17 William Allen Runyan Freight-car door.
US3719760A (en) * 1968-01-29 1973-03-06 Bayer Ag N-trityl-imidazolium salts as a fungicide
US3811449A (en) * 1972-03-08 1974-05-21 Becton Dickinson Co Dilating apparatus and method
US4350151A (en) * 1981-03-12 1982-09-21 Lone Star Medical Products, Inc. Expanding dilator
US4369790A (en) * 1981-03-05 1983-01-25 Mccarthy John M Catheter
US4401433A (en) * 1980-06-13 1983-08-30 Luther Ronald B Apparatus for advancing oversized catheter through cannula, and the like
US4449532A (en) * 1980-07-08 1984-05-22 Karl Storz Dilator to facilitate endoscope insertion into the body
US4451256A (en) * 1981-05-06 1984-05-29 Intermedicat Gmbh Catheter set
US4573448A (en) * 1983-10-05 1986-03-04 Pilling Co. Method for decompressing herniated intervertebral discs
US4601710A (en) * 1983-08-24 1986-07-22 Endotherapeutics Corporation Trocar assembly
US4686984A (en) * 1984-03-15 1987-08-18 Richard Wolf Gmbh Catheter for widening a puncture channel
US4802479A (en) * 1986-10-31 1989-02-07 C. R. Bard, Inc. Hand-held instrument for implanting, dispensing, and inflating an inflatable membrane
US4862891A (en) * 1988-03-14 1989-09-05 Canyon Medical Products Device for sequential percutaneous dilation
US4981482A (en) * 1987-08-20 1991-01-01 Kazuo Ichikawa Device for forming an inserting hole for an endoscope
US4994027A (en) * 1988-06-08 1991-02-19 Farrell Edward M Percutaneous femoral bypass system
US5002557A (en) * 1989-04-06 1991-03-26 Hasson Harrith M Laparoscopic cannula
US5114407A (en) * 1990-08-30 1992-05-19 Ethicon, Inc. Safety mechanism for trocar
US5176651A (en) * 1991-04-01 1993-01-05 Dexide, Inc. Combination surgical trocar housing and selective reducer sleeve assembly
US5176697A (en) * 1989-04-06 1993-01-05 Hasson Harrith M Laparoscopic cannula
US5183464A (en) * 1991-05-17 1993-02-02 Interventional Thermodynamics, Inc. Radially expandable dilator
US5188118A (en) * 1990-11-07 1993-02-23 Terwilliger Richard A Automatic biopsy instrument with independently actuated stylet and cannula
US5195506A (en) * 1991-10-18 1993-03-23 Life Medical Products, Inc. Surgical retractor for puncture operation
US5224952A (en) * 1988-07-06 1993-07-06 Ethicon, Inc. Safety trocar
US5241972A (en) * 1991-05-03 1993-09-07 Meditron Devices, Inc. Method for debulking tissue to remove pressure on a nerve
US5280782A (en) * 1991-11-15 1994-01-25 Wilk Peter J Variable length laparoscopic retractor and associated method of use
US5290243A (en) * 1992-07-16 1994-03-01 Technalytics, Inc. Trocar system
US5312417A (en) * 1992-07-29 1994-05-17 Wilk Peter J Laparoscopic cannula assembly and associated method
US5324261A (en) * 1991-01-04 1994-06-28 Medtronic, Inc. Drug delivery balloon catheter with line of weakness
US5342382A (en) * 1991-01-15 1994-08-30 Ethicon, Inc. Surgical trocar
US5407430A (en) * 1994-03-21 1995-04-18 Peters; Michael J. Intravenous catheter
US5486190A (en) * 1991-04-30 1996-01-23 United States Surgical Corporation Safety trocar
US5505710A (en) * 1994-08-22 1996-04-09 C. R. Bard, Inc. Telescoping probe
US5512037A (en) * 1994-05-12 1996-04-30 United States Surgical Corporation Percutaneous surgical retractor
US5613950A (en) * 1988-07-22 1997-03-25 Yoon; Inbae Multifunctional manipulating instrument for various surgical procedures
US5624447A (en) * 1995-03-20 1997-04-29 Othy, Inc. Surgical tool guide and entry hole positioner
US5647857A (en) * 1995-03-16 1997-07-15 Endotex Interventional Systems, Inc. Protective intraluminal sheath
US5707359A (en) * 1995-11-14 1998-01-13 Bufalini; Bruno Expanding trocar assembly
US5713870A (en) * 1991-11-27 1998-02-03 Yoon; Inbae Retractable safety penetrating instrument with laterally extendable spring strip
US5728097A (en) * 1992-03-17 1998-03-17 Sdgi Holding, Inc. Method for subcutaneous suprafascial internal fixation
US5743881A (en) * 1995-11-03 1998-04-28 Aptec Medical Corporation Laparoscopic surgical instrument and method of using same
US5752969A (en) * 1993-06-17 1998-05-19 Sofamor S.N.C. Instrument for the surgical treatment of an intervertebral disc by the anterior route
US5772678A (en) * 1995-10-20 1998-06-30 Inlet Medical, Inc. Retractable disposable tip reusable trocar obturator
US5776156A (en) * 1995-09-05 1998-07-07 United States Surgical Corporation Endoscopic cutting instrument
US5782800A (en) * 1988-07-22 1998-07-21 Yoon; Inbae Expandable multifunctional manipulating instruments for various medical procedures and methods therefor
US5792044A (en) * 1996-03-22 1998-08-11 Danek Medical, Inc. Devices and methods for percutaneous surgery
US5810866A (en) * 1991-11-27 1998-09-22 Yoon; Inbae Automatic retractable safety penetrating instrument for portal sleeve introduction
US5810721A (en) * 1996-03-04 1998-09-22 Heartport, Inc. Soft tissue retractor and method for providing surgical access
US5957902A (en) * 1998-09-28 1999-09-28 Teves; Leonides Y. Surgical tool for enlarging puncture opening made by trocar
US6030364A (en) * 1997-10-03 2000-02-29 Boston Scientific Corporation Apparatus and method for percutaneous placement of gastro-intestinal tubes
US6048309A (en) * 1996-03-04 2000-04-11 Heartport, Inc. Soft tissue retractor and delivery device therefor
US6053935A (en) * 1996-11-08 2000-04-25 Boston Scientific Corporation Transvaginal anchor implantation device
US6117174A (en) * 1998-09-16 2000-09-12 Nolan; Wesley A. Spinal implant device
US6197041B1 (en) * 1991-06-26 2001-03-06 United States Surgical Corporation Trocar
US6200322B1 (en) * 1999-08-13 2001-03-13 Sdgi Holdings, Inc. Minimal exposure posterior spinal interbody instrumentation and technique
US6206922B1 (en) * 1995-03-27 2001-03-27 Sdgi Holdings, Inc. Methods and instruments for interbody fusion
US6206826B1 (en) * 1997-12-18 2001-03-27 Sdgi Holdings, Inc. Devices and methods for percutaneous surgery
US6213957B1 (en) * 1995-09-08 2001-04-10 United States Surgical Corporation Apparatus and method for removing tissue
US6217509B1 (en) * 1996-03-22 2001-04-17 Sdgi Holdings, Inc. Devices and methods for percutaneous surgery
US6228058B1 (en) * 1997-04-03 2001-05-08 Core Dynamics, Inc. Sleeve trocar with penetration indicator
US6264676B1 (en) * 1996-11-08 2001-07-24 Scimed Life Systems, Inc. Protective sheath for transvaginal anchor implantation devices
US20010012950A1 (en) * 1997-10-01 2001-08-09 Srinivas Nishtala Dilation systems and related methods
US6293952B1 (en) * 1997-07-31 2001-09-25 Circon Corporation Medical instrument system for piercing through tissue
US6293909B1 (en) * 1998-08-07 2001-09-25 Scimed Life Systems, Inc. Device and method of using a surgical assembly with mesh sheath
US20020001476A1 (en) * 1998-06-26 2002-01-03 Tomoyuki Nagamine Image forming apparatus
US6348053B1 (en) * 1996-11-12 2002-02-19 Triage Medical, Inc. Bone fixation device
US6364897B1 (en) * 1993-02-04 2002-04-02 Peter M. Bonutti Method and apparatus for positioning a suture anchor
US20020087152A1 (en) * 2001-01-04 2002-07-04 Endocare, Inc. Systems and methods for delivering a probe into tissue
US6428541B1 (en) * 1998-04-09 2002-08-06 Sdgi Holdings, Inc. Method and instrumentation for vertebral interbody fusion
US6428556B1 (en) * 1999-08-25 2002-08-06 Origin Medsystems, Inc. Longitudinal dilator and method
US6447540B1 (en) * 1996-11-15 2002-09-10 Cook Incorporated Stent deployment device including splittable sleeve containing the stent
US6447527B1 (en) * 1998-04-23 2002-09-10 Ronald J. Thompson Apparatus and methods for the penetration of tissue
US6511481B2 (en) * 2001-03-30 2003-01-28 Triage Medical, Inc. Method and apparatus for fixation of proximal femoral fractures
US20030083688A1 (en) * 2001-10-30 2003-05-01 Simonson Robert E. Configured and sized cannula
US6562049B1 (en) * 2000-03-01 2003-05-13 Cook Vascular Incorporated Medical introducer apparatus
US6562046B2 (en) * 1999-11-23 2003-05-13 Sdgi Holdings, Inc. Screw delivery system and method
US6582441B1 (en) * 2000-02-24 2003-06-24 Advanced Bionics Corporation Surgical insertion tool
US6582437B2 (en) * 1999-08-26 2003-06-24 Sdgi Holdings, Inc. Devices and methods for implanting fusion cages
US6589240B2 (en) * 2001-08-28 2003-07-08 Rex Medical, L.P. Tissue biopsy apparatus with collapsible cutter
US6592553B2 (en) * 2000-07-05 2003-07-15 Cardiac Pacemakers, Inc. Introducer assembly and method therefor
US6607530B1 (en) * 1999-05-10 2003-08-19 Highgate Orthopedics, Inc. Systems and methods for spinal fixation
US6679833B2 (en) * 1996-03-22 2004-01-20 Sdgi Holdings, Inc. Devices and methods for percutaneous surgery
US20040019359A1 (en) * 2002-07-24 2004-01-29 Worley Seth J. Telescopic introducer with a compound curvature for inducing alignment and method of using the same
US6685706B2 (en) * 2001-11-19 2004-02-03 Triage Medical, Inc. Proximal anchors for bone fixation system
US6689152B2 (en) * 1998-09-09 2004-02-10 Edwards Lifesciences Corp. Introducer/dilator with balloon protection and methods of use
US20040059339A1 (en) * 2002-09-19 2004-03-25 Roehm Thomas E. Oval dilator and retractor set and method
US20040059350A1 (en) * 1992-09-04 2004-03-25 Scimed Life Systems, Inc. Suturing instruments and methods of use
US6743166B2 (en) * 1999-02-12 2004-06-01 Karl Storz Gmbh & Co. Kg Apparatus for introducing an intubation tube into the trachea
US6746451B2 (en) * 2001-06-01 2004-06-08 Lance M. Middleton Tissue cavitation device and method
US20040147877A1 (en) * 2003-01-27 2004-07-29 Heuser Richard R Catheter introducer system
US20040158258A1 (en) * 2003-02-12 2004-08-12 Bonati Alfred O. Method for removing orthopaedic hardware
US7025746B2 (en) * 2001-12-26 2006-04-11 Yale University Vascular access device
US7172612B2 (en) * 2000-12-12 2007-02-06 Olympus Corporation Trocar and trocar system

Family Cites Families (250)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US1541453A (en) * 1922-12-20 1925-06-09 Watkins Clayton Stuart Demountable rim and wheell for automobiles and other vehicles
US3260656A (en) * 1962-09-27 1966-07-12 Corning Glass Works Method and apparatus for electrolytically determining a species in a fluid
US3653841A (en) * 1969-12-19 1972-04-04 Hoffmann La Roche Methods and compositions for determining glucose in blood
US3719564A (en) * 1971-05-10 1973-03-06 Philip Morris Inc Method of determining a reducible gas concentration and sensor therefor
US3837339A (en) * 1972-02-03 1974-09-24 Whittaker Corp Blood glucose level monitoring-alarm system and method therefor
US4184429A (en) * 1972-02-09 1980-01-22 Max Datwyler & Co. Constant bevel doctor blade and method and apparatus using same
US3908657A (en) * 1973-01-15 1975-09-30 Univ Johns Hopkins System for continuous withdrawal of blood
US4100048A (en) * 1973-09-20 1978-07-11 U.S. Philips Corporation Polarographic cell
US3911901A (en) * 1974-07-24 1975-10-14 Gen Electric In vivo hydrogen ion sensor
US3972320A (en) * 1974-08-12 1976-08-03 Gabor Ujhelyi Kalman Patient monitoring system
US3979274A (en) * 1975-09-24 1976-09-07 The Yellow Springs Instrument Company, Inc. Membrane for enzyme electrodes
US4016866A (en) * 1975-12-18 1977-04-12 General Electric Company Implantable electrochemical sensor
US4055175A (en) * 1976-05-07 1977-10-25 Miles Laboratories, Inc. Blood glucose control apparatus
DE2625834B2 (en) * 1976-06-09 1978-10-12 Boehringer Mannheim Gmbh, 6800 Mannheim Method for the determination of substrates or enzyme activities
US4076596A (en) * 1976-10-07 1978-02-28 Leeds & Northrup Company Apparatus for electrolytically determining a species in a fluid and method of use
FR2387659A1 (en) * 1977-04-21 1978-11-17 Armines GLYCEMIA CONTROL AND REGULATION DEVICE
US4098574A (en) * 1977-08-01 1978-07-04 Eastman Kodak Company Glucose detection system free from fluoride-ion interference
JPS5912135B2 (en) * 1977-09-28 1984-03-21 松下電器産業株式会社 enzyme electrode
US4151845A (en) * 1977-11-25 1979-05-01 Miles Laboratories, Inc. Blood glucose control apparatus
DK151000C (en) * 1978-02-17 1988-06-13 Radiometer As PROCEDURE AND APPARATUS FOR DETERMINING A PATIENT'S IN VIVO PLASMA-PH VALUE
US4172770A (en) * 1978-03-27 1979-10-30 Technicon Instruments Corporation Flow-through electrochemical system analytical method
HU177369B (en) * 1978-09-08 1981-09-28 Radelkis Electrokemiai Industrial molecule-selective sensing device and method for producing same
US4247297A (en) * 1979-02-23 1981-01-27 Miles Laboratories, Inc. Test means and method for interference resistant determination of oxidizing substances
US4573994A (en) * 1979-04-27 1986-03-04 The Johns Hopkins University Refillable medication infusion apparatus
US4458686A (en) * 1979-08-02 1984-07-10 Children's Hospital Medical Center Cutaneous methods of measuring body substances
US4401122A (en) * 1979-08-02 1983-08-30 Children's Hospital Medical Center Cutaneous methods of measuring body substances
US4450842A (en) * 1980-04-25 1984-05-29 Cordis Corporation Solid state reference electrode
US4340458A (en) * 1980-06-02 1982-07-20 Joslin Diabetes Center, Inc. Glucose sensor
US4356074A (en) * 1980-08-25 1982-10-26 The Yellow Springs Instrument Company, Inc. Substrate specific galactose oxidase enzyme electrodes
US4404066A (en) * 1980-08-25 1983-09-13 The Yellow Springs Instrument Company Method for quantitatively determining a particular substrate catalyzed by a multisubstrate enzyme
US4352960A (en) * 1980-09-30 1982-10-05 Baptist Medical Center Of Oklahoma, Inc. Magnetic transcutaneous mount for external device of an associated implant
US4390621A (en) * 1980-12-15 1983-06-28 Miles Laboratories, Inc. Method and device for detecting glucose concentration
US4436094A (en) * 1981-03-09 1984-03-13 Evreka, Inc. Monitor for continuous in vivo measurement of glucose concentration
AT369254B (en) * 1981-05-07 1982-12-27 Otto Dipl Ing Dr Tech Prohaska MEDICAL PROBE
FR2508305B1 (en) * 1981-06-25 1986-04-11 Slama Gerard DEVICE FOR CAUSING A LITTLE BITE TO COLLECT A BLOOD DROP
US4440175A (en) * 1981-08-10 1984-04-03 University Patents, Inc. Membrane electrode for non-ionic species
EP0078636B2 (en) * 1981-10-23 1997-04-02 MediSense, Inc. Sensor for components of a liquid mixture
US4431004A (en) * 1981-10-27 1984-02-14 Bessman Samuel P Implantable glucose sensor
JPS58153154A (en) * 1982-03-09 1983-09-12 Ajinomoto Co Inc Qualified electrode
US4581336A (en) * 1982-04-26 1986-04-08 Uop Inc. Surface-modified electrodes
DE3221339A1 (en) * 1982-06-05 1983-12-08 Basf Ag, 6700 Ludwigshafen METHOD FOR THE ELECTROCHEMICAL HYDRATION OF NICOTINAMIDADENINE-DINUCLEOTIDE
US4427770A (en) * 1982-06-14 1984-01-24 Miles Laboratories, Inc. High glucose-determining analytical element
DE3228551A1 (en) * 1982-07-30 1984-02-02 Siemens AG, 1000 Berlin und 8000 München METHOD FOR DETERMINING SUGAR CONCENTRATION
US4534356A (en) * 1982-07-30 1985-08-13 Diamond Shamrock Chemicals Company Solid state transcutaneous blood gas sensors
US4571292A (en) * 1982-08-12 1986-02-18 Case Western Reserve University Apparatus for electrochemical measurements
US4461691A (en) * 1983-02-10 1984-07-24 The United States Of America As Represented By The United States Department Of Energy Organic conductive films for semiconductor electrodes
US4679562A (en) * 1983-02-16 1987-07-14 Cardiac Pacemakers, Inc. Glucose sensor
IT1170375B (en) * 1983-04-19 1987-06-03 Giuseppe Bombardieri Implantable device for measuring body fluid parameters
CA1218704A (en) * 1983-05-05 1987-03-03 Graham Davis Assay systems using more than one enzyme
US4650547A (en) * 1983-05-19 1987-03-17 The Regents Of The University Of California Method and membrane applicable to implantable sensor
US4524114A (en) * 1983-07-05 1985-06-18 Allied Corporation Bifunctional air electrode
US4538616A (en) * 1983-07-25 1985-09-03 Robert Rogoff Blood sugar level sensing and monitoring transducer
US4543955A (en) * 1983-08-01 1985-10-01 Cordis Corporation System for controlling body implantable action device
US4655880A (en) * 1983-08-01 1987-04-07 Case Western Reserve University Apparatus and method for sensing species, substances and substrates using oxidase
US4522690A (en) * 1983-12-01 1985-06-11 Honeywell Inc. Electrochemical sensing of carbon monoxide
US4840893A (en) * 1983-12-16 1989-06-20 Medisense, Inc. Electrochemical assay for nucleic acids and nucleic acid probes
JPS60135756A (en) * 1983-12-24 1985-07-19 Ngk Insulators Ltd Production of electrochemical cell
EP0179823B1 (en) * 1984-04-30 1989-07-12 Stiftung, R. E. Process for the sensitization of an oxidoreduction photocalatyst, and photocatalyst thus obtained
DK8601218A (en) * 1984-07-18 1986-03-17
US4820399A (en) * 1984-08-31 1989-04-11 Shimadzu Corporation Enzyme electrodes
CA1254091A (en) * 1984-09-28 1989-05-16 Vladimir Feingold Implantable medication infusion system
US4721601A (en) * 1984-11-23 1988-01-26 Massachusetts Institute Of Technology Molecule-based microelectronic devices
US4717673A (en) * 1984-11-23 1988-01-05 Massachusetts Institute Of Technology Microelectrochemical devices
JPH0617889B2 (en) * 1984-11-27 1994-03-09 株式会社日立製作所 Biochemical sensor
GB8500729D0 (en) * 1985-01-11 1985-02-13 Hill H A O Surface-modified electrode
US4627445A (en) * 1985-04-08 1986-12-09 Garid, Inc. Glucose medical monitoring system
US4671288A (en) * 1985-06-13 1987-06-09 The Regents Of The University Of California Electrochemical cell sensor for continuous short-term use in tissues and blood
WO1986007632A1 (en) * 1985-06-21 1986-12-31 Matsushita Electric Industrial Co., Ltd. Biosensor and method of manufacturing same
US4796634A (en) * 1985-08-09 1989-01-10 Lawrence Medical Systems, Inc. Methods and apparatus for monitoring cardiac output
US4805624A (en) * 1985-09-09 1989-02-21 The Montefiore Hospital Association Of Western Pa Low-potential electrochemical redox sensors
US4680268A (en) * 1985-09-18 1987-07-14 Children's Hospital Medical Center Implantable gas-containing biosensor and method for measuring an analyte such as glucose
US4890620A (en) * 1985-09-20 1990-01-02 The Regents Of The University Of California Two-dimensional diffusion glucose substrate sensing electrode
CA1254616A (en) * 1985-11-11 1989-05-23 Calum J. Mcneil Electrochemical enzymic assay procedures
GB8529300D0 (en) * 1985-11-28 1986-01-02 Ici Plc Membrane
US4776944A (en) * 1986-03-20 1988-10-11 Jiri Janata Chemical selective sensors utilizing admittance modulated membranes
US4685463A (en) * 1986-04-03 1987-08-11 Williams R Bruce Device for continuous in vivo measurement of blood glucose concentrations
US4726378A (en) * 1986-04-11 1988-02-23 Minnesota Mining And Manufacturing Company Adjustable magnetic supercutaneous device and transcutaneous coupling apparatus
US4757022A (en) * 1986-04-15 1988-07-12 Markwell Medical Institute, Inc. Biological fluid measuring device
US4909908A (en) * 1986-04-24 1990-03-20 Pepi Ross Electrochemical cncentration detector method
US4795542A (en) * 1986-04-24 1989-01-03 St. Jude Medical, Inc. Electrochemical concentration detector device
DE3614821A1 (en) * 1986-05-02 1987-11-05 Siemens Ag IMPLANTABLE, CALIBRABLE MEASURING DEVICE FOR A BODY SUBSTANCE AND CALIBRATION METHOD
CA1283447C (en) * 1986-06-20 1991-04-23 John W. Parce Zero volume electrochemical cell
US4764416A (en) * 1986-07-01 1988-08-16 Mitsubishi Denki Kabushiki Kaisha Electric element circuit using oxidation-reduction substances
US4917800A (en) * 1986-07-07 1990-04-17 Bend Research, Inc. Functional, photochemically active, and chemically asymmetric membranes by interfacial polymerization of derivatized multifunctional prepolymers
US4726716A (en) * 1986-07-21 1988-02-23 Mcguire Thomas V Fastener for catheter
US4894137A (en) * 1986-09-12 1990-01-16 Omron Tateisi Electronics Co. Enzyme electrode
DE3700119A1 (en) * 1987-01-03 1988-07-14 Inst Diabetestechnologie Gemei IMPLANTABLE ELECTROCHEMICAL SENSOR
US4848351A (en) * 1987-03-04 1989-07-18 Sentry Medical Products, Inc. Medical electrode assembly
US4759828A (en) * 1987-04-09 1988-07-26 Nova Biomedical Corporation Glucose electrode and method of determining glucose
US4822337A (en) * 1987-06-22 1989-04-18 Stanley Newhouse Insulin delivery method and apparatus
JPH07122624B2 (en) * 1987-07-06 1995-12-25 ダイキン工業株式会社 Biosensor
GB8718430D0 (en) * 1987-08-04 1987-09-09 Ici Plc Sensor
US4874500A (en) * 1987-07-15 1989-10-17 Sri International Microelectrochemical sensor and sensor array
US4815469A (en) * 1987-10-08 1989-03-28 Siemens-Pacesetter, Inc. Implantable blood oxygen sensor and method of use
US4813424A (en) * 1987-12-23 1989-03-21 University Of New Mexico Long-life membrane electrode for non-ionic species
US4923442A (en) * 1988-05-02 1990-05-08 Cryomedical Sciences Inc. Blood substitute
US5831066A (en) 1988-12-22 1998-11-03 The Trustees Of The University Of Pennsylvania Regulation of bcl-2 gene expression
WO1991004753A1 (en) * 1989-10-02 1991-04-18 Cetus Corporation Conjugates of antisense oligonucleotides and therapeutic uses thereof
GB9123947D0 (en) * 1991-11-12 1992-01-02 Imp Cancer Res Tech Therapeutic compounds
CA2140343A1 (en) * 1992-07-17 1994-02-03 Sean M. Sullivan Method and reagent for treatment of animal diseases
US6001992A (en) 1999-01-07 1999-12-14 Isis Pharmaceuticals Inc. Antisense modulation of novel anti-apoptotic bcl-2-related proteins
US20040204380A1 (en) 1999-01-07 2004-10-14 Ackermann Elizabeth J Antisense modulation of novel anti-apoptotic bcl-2-related proteins
US20020086321A1 (en) 1993-02-02 2002-07-04 Craig Ruth W. Myeloid cell leukemia associated gene MCL-1
US5731294A (en) * 1993-07-27 1998-03-24 Hybridon, Inc. Inhibition of neovasularization using VEGF-specific oligonucleotides
US6410322B1 (en) * 1993-07-27 2002-06-25 Hybridon Inc Antisense oligonucleotide inhibition of vascular endothelial growth factor expression
US5641756A (en) * 1993-07-27 1997-06-24 Hybridon, Inc. Modified VEGF oligonucleotides
CA2183254A1 (en) 1994-02-14 1995-08-17 Jasminder Weinstein Mammalian cell cycle protein
US6150092A (en) * 1994-06-27 2000-11-21 Taogosei Company, Ltd. Antisense nucleic acid compound targeted to VEGF
US5830879A (en) * 1995-10-02 1998-11-03 St. Elizabeth's Medical Center Of Boston, Inc. Treatment of vascular injury using vascular endothelial growth factor
US6346398B1 (en) 1995-10-26 2002-02-12 Ribozyme Pharmaceuticals, Inc. Method and reagent for the treatment of diseases or conditions related to levels of vascular endothelial growth factor receptor
WO1997021808A1 (en) * 1995-12-08 1997-06-19 Hybridon, Inc. Modified vegf antisense oligonucleotides
AU1686997A (en) * 1995-12-08 1997-06-27 Hybridon, Inc. Modified vegf antisense oligonucleotides for treatment of skin disorders
US6716575B2 (en) 1995-12-18 2004-04-06 Sugen, Inc. Diagnosis and treatment of AUR1 and/or AUR2 related disorders
EP0910634A2 (en) * 1996-04-17 1999-04-28 Hoechst Marion Roussel Deutschland GmbH ANTISENSE INHIBITORS OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEgF/VPF) EXPRESSION
US20050261485A1 (en) 1996-05-23 2005-11-24 Toagosei Co., Ltd., A Japan Corporation Method of producing antisense oligonucleotide
US7223849B1 (en) 1996-07-01 2007-05-29 Genesense Technologies Inc. Oligonucleotides from the untranslated regions of housekeeping genes and methods of using same to modulate cell growth
AU6237198A (en) * 1996-12-19 1998-07-15 Isis Pharmaceuticals, Inc. Large-scale purification of full length oligonucleotides by solid-liquid affinity extraction
US6800744B1 (en) * 1997-07-02 2004-10-05 Genome Therapeutics Corporation Nucleic acid and amino acid sequences relating to Streptococcus pneumoniae for diagnostics and therapeutics
JPH1142091A (en) * 1997-07-25 1999-02-16 Toagosei Co Ltd Anti-sense nucleic acid compound
CA2302317A1 (en) * 1997-08-26 1999-03-04 Gliatech, Inc. A process for inhibiting complement activation via the alternative pathway
US6046319A (en) 1997-10-22 2000-04-04 University Technologies International, Inc. Antisense oligodeoxynucleotides regulating expression of TNF-α
US6506559B1 (en) 1997-12-23 2003-01-14 Carnegie Institute Of Washington Genetic inhibition by double-stranded RNA
CA2362320A1 (en) 1998-01-29 1999-08-05 The Trustees Of Columbia University In The City Of New York Human hairless gene, protein and uses thereof
US6111086A (en) 1998-02-27 2000-08-29 Scaringe; Stephen A. Orthoester protecting groups
CA2325058C (en) * 1998-04-03 2011-07-12 Wisconsin Alumni Research Foundation Mammalian tolloid-like gene and protein
US20030228597A1 (en) 1998-04-13 2003-12-11 Cowsert Lex M. Identification of genetic targets for modulation by oligonucleotides and generation of oligonucleotides for gene modulation
DE69919869T2 (en) * 1998-06-10 2005-09-29 Biognostik Gesellschaft für Biomolekulare Diagnostik mbH STIMULATION OF THE IMMUNE SYSTEM
US6007995A (en) * 1998-06-26 1999-12-28 Isis Pharmaceuticals Inc. Antisense inhibition of TNFR1 expression
US20030096775A1 (en) * 2001-10-23 2003-05-22 Isis Pharmaceuticals Inc. Antisense modulation of complement component C3 expression
WO2000001393A2 (en) 1998-07-02 2000-01-13 The Trustees Of Columbia University In The City Of New York OLIGONUCLEOTIDE INHIBITORS OF bcl-xL
US6228642B1 (en) * 1998-10-05 2001-05-08 Isis Pharmaceuticals, Inc. Antisense oligonucleotide modulation of tumor necrosis factor-(α) (TNF-α) expression
US6172216B1 (en) 1998-10-07 2001-01-09 Isis Pharmaceuticals Inc. Antisense modulation of BCL-X expression
AU1705100A (en) 1998-10-09 2000-05-01 Musc Foundation For Research Development Blocking factor b to treat complement-mediated immune disease
EP1124950B1 (en) * 1998-10-26 2006-07-12 Avi Biopharma, Inc. Morpholino based p53 antisense oligonucleotide, and uses thereof
WO2000027414A2 (en) * 1998-11-06 2000-05-18 Basf Aktiengesellschaft Inhibition of the formation of vascular hyperpermeability
US5958773A (en) 1998-12-17 1999-09-28 Isis Pharmaceuticals Inc. Antisense modulation of AKT-1 expression
WO2000048991A1 (en) * 1999-02-18 2000-08-24 The Regents Of The University Of California Salicylamide-lanthanide complexes for use as luminescent markers
WO2000061770A2 (en) * 1999-04-08 2000-10-19 Chiron Corporation Enhancement of the immune response for vaccine and gene therapy applications
JP4638098B2 (en) 1999-06-14 2011-02-23 キャンサー・リサーチ・テクノロジー・リミテッド Cancer treatment
US6770633B1 (en) * 1999-10-26 2004-08-03 Immusol, Inc. Ribozyme therapy for the treatment of proliferative skin and eye diseases
US7179796B2 (en) 2000-01-18 2007-02-20 Isis Pharmaceuticals, Inc. Antisense modulation of PTP1B expression
US8202979B2 (en) 2002-02-20 2012-06-19 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid
BR0107536A (en) 2000-03-30 2004-03-02 Whitehead Biomedical Inst Isolated rna, soluble extract, method for producing rna from about 21 to about 23 nucleotides in length; isolated dna
JP2004501637A (en) * 2000-06-26 2004-01-22 スージェン・インコーポレーテッド New protease
WO2002031141A2 (en) * 2000-10-13 2002-04-18 Institut De Cardiologie De Montreal Antisense oligonucleotide directed toward mammalian vegf receptor genes and uses thereof
AU2002243429A1 (en) * 2000-10-24 2002-06-24 Isis Pharmaceuticals, Inc. Antisense modulation of tnfr1 expression
MXPA03003856A (en) 2000-11-01 2004-04-20 Bki Holding Corp Cellulose ethers and method of preparing the same.
WO2002044321A2 (en) 2000-12-01 2002-06-06 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Rna interference mediating small rna molecules
US20020150945A1 (en) * 2000-12-28 2002-10-17 Cell Therapeutics, Inc. Methods for making polynucleotide libraries, polynucleotide arrays, and cell libraries for high-throughput genomics analysis
US20030143597A1 (en) 2000-12-28 2003-07-31 Finney Robert E. Methods for making polynucleotide libraries, polynucleotide arrays, and cell libraries for high-throughput genomics analysis
EP1353676A4 (en) 2000-12-29 2006-05-31 Alteon Inc Method for treating fibrotic diseases or other indications
WO2003035869A1 (en) 2001-10-26 2003-05-01 Ribopharma Ag Use of a double-stranded ribonucleic acid for specifically inhibiting the expression of a given target gene
EP1372690A4 (en) * 2001-03-01 2005-08-24 Millennium Pharm Inc 93870, a human g-protein coupled receptor and uses therefor
EP1386004A4 (en) 2001-04-05 2005-02-16 Ribozyme Pharm Inc Modulation of gene expression associated with inflammation proliferation and neurite outgrowth, using nucleic acid based technologies
WO2002085285A2 (en) 2001-04-18 2002-10-31 Wyeth Methods and reagents for regulating bone and cartilage formation
WO2002085308A2 (en) * 2001-04-24 2002-10-31 Epigenesis Pharmaceuticals, Inc. Antisense and anti-inflammatory based compositions to treat respiratory disorders
WO2002085309A2 (en) * 2001-04-24 2002-10-31 Epigenesis Pharmaceuticals, Inc. Composition, formulations & kits for treatment of respiratory & lung disease with anti-sense oligonucleotides & a bronchodilating agent
US20040219671A1 (en) 2002-02-20 2004-11-04 Sirna Therapeutics, Inc. RNA interference mediated treatment of parkinson disease using short interfering nucleic acid (siNA)
WO2003070910A2 (en) * 2002-02-20 2003-08-28 Ribozyme Pharmaceuticals, Incorporated INHIBITION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) AND VEGF RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20050130181A1 (en) 2001-05-18 2005-06-16 Sirna Therapeutics, Inc. RNA interference mediated inhibition of wingless gene expression using short interfering nucleic acid (siNA)
US20050239731A1 (en) 2001-05-18 2005-10-27 Sirna Therapeutics, Inc. RNA interference mediated inhibition of MAP kinase gene expression using short interfering nucleic acid (siNA)
US20050227935A1 (en) 2001-05-18 2005-10-13 Sirna Therapeutics, Inc. RNA interference mediated inhibition of TNF and TNF receptor gene expression using short interfering nucleic acid (siNA)
US20050048529A1 (en) 2002-02-20 2005-03-03 Sirna Therapeutics, Inc. RNA interference mediated inhibition of intercellular adhesion molecule (ICAM) gene expression using short interfering nucleic acid (siNA)
WO2003070897A2 (en) * 2002-02-20 2003-08-28 Ribozyme Pharmaceuticals, Incorporated RNA INTERFERENCE MEDIATED INHIBITION OF TNF AND TNF RECEPTOR SUPERFAMILY GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20050176025A1 (en) * 2001-05-18 2005-08-11 Sirna Therapeutics, Inc. RNA interference mediated inhibition of B-cell CLL/Lymphoma-2 (BCL-2) gene expression using short interfering nucleic acid (siNA)
US20050148530A1 (en) 2002-02-20 2005-07-07 Sirna Therapeutics, Inc. RNA interference mediated inhibition of vascular endothelial growth factor and vascular endothelial growth factor receptor gene expression using short interfering nucleic acid (siNA)
CA2448320A1 (en) * 2001-05-29 2002-12-05 Sirna Therapeutics, Inc. Ribozyme based treatment of female reproductive diseases
EP1390472A4 (en) 2001-05-29 2004-11-17 Sirna Therapeutics Inc NUCLEIC ACID TREATMENT OF DISEASES OR CONDITIONS ASSOCIATED WITH RAS, HER2 AND HIV RATES
WO2003006424A1 (en) 2001-07-10 2003-01-23 4Sc Ag Novel compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents
JP4917225B2 (en) 2001-09-28 2012-04-18 ローム株式会社 Semiconductor device
US6734017B2 (en) * 2001-09-28 2004-05-11 Isis Pharmaceuticals, Inc. Antisense modulation of vascular endothelial growth factor receptor-2 expression
WO2003035870A1 (en) 2001-10-26 2003-05-01 Ribopharma Ag Drug for treating a carcinoma of the pancreas
US20030157030A1 (en) 2001-11-02 2003-08-21 Insert Therapeutics, Inc. Methods and compositions for therapeutic use of rna interference
US20040063654A1 (en) 2001-11-02 2004-04-01 Davis Mark E. Methods and compositions for therapeutic use of RNA interference
FR2832154B1 (en) 2001-11-09 2007-03-16 Centre Nat Rech Scient OLIGONUCLEOTIDES INHIBITORS AND THEIR USE FOR SPECIFICALLY REPRESSING A GENE
US20030186903A1 (en) 2001-11-23 2003-10-02 Isis Pharmaceuticals Inc. Antisense modulation of MyD88 expression
EP2014674B1 (en) 2001-11-26 2014-02-12 Laboratoire Biodim Protein-protein interactions in human immunodeficiency virus
US6965025B2 (en) 2001-12-10 2005-11-15 Isis Pharmaceuticals, Inc. Antisense modulation of connective tissue growth factor expression
GB0130955D0 (en) * 2001-12-24 2002-02-13 Cancer Res Ventures Expression system
KR100441894B1 (en) * 2002-01-26 2004-07-27 한국전자통신연구원 Micro-integrated near-field optical recording head and optical recording system using the same
EP2221377B2 (en) 2002-02-01 2017-05-17 Life Technologies Corporation Oligonucleotide compositions with enhanced efficiency
AU2003207708A1 (en) * 2002-02-20 2003-09-09 Sirna Therapeutics, Inc. Rna interference mediated inhibition of map kinase genes
EP1436314A4 (en) 2002-02-20 2005-08-10 Sirna Therapeutics Inc RNA MEDIATION INHIBITION OF GENE EXPRESSION OF CYCLIN D1 USING SHORT INTERFERENCE NUCLEIC ACID (SINA)
EP1442143A4 (en) * 2002-02-20 2005-02-16 Sirna Therapeutics Inc INHIBITION OF RNA INTERFERENCE-INDUCED BCL2 GENE EXPRESSION USING SMALL INTERFERING NUCLEIC ACIDS (SINA)
CA2479530A1 (en) 2002-03-20 2003-10-02 Massachusetts Institute Of Technology Hiv therapeutic
CA2513149A1 (en) 2002-03-29 2003-10-16 Yun Yen A human ribonucleotide reductase m2 subunit
US20030224512A1 (en) 2002-05-31 2003-12-04 Isis Pharmaceuticals Inc. Antisense modulation of beta-site APP-cleaving enzyme expression
AU2003237570A1 (en) 2002-05-13 2003-11-11 Salviac Limited Catheter system with procedural catheter and embolic proctection system
US20040101857A1 (en) 2002-11-23 2004-05-27 Isis Pharmaceuticals Inc. Modulation of cytokine-inducible kinase expression
US20040009946A1 (en) 2002-05-23 2004-01-15 Ceptyr, Inc. Modulation of PTP1B expression and signal transduction by RNA interference
US20040102391A1 (en) 2002-11-21 2004-05-27 Isis Pharmaceuticals Inc. Modulation of Gankyrin expression
WO2003106974A2 (en) 2002-06-18 2003-12-24 Irm Llc Diagnosis and treatment of chemoresistant tumors
US7148342B2 (en) * 2002-07-24 2006-12-12 The Trustees Of The University Of Pennyslvania Compositions and methods for sirna inhibition of angiogenesis
US6906186B1 (en) 2002-07-30 2005-06-14 Isis Pharmaceuticals, Inc. Antisense modulation of polo-like kinase expression
US20040029275A1 (en) 2002-08-10 2004-02-12 David Brown Methods and compositions for reducing target gene expression using cocktails of siRNAs or constructs expressing siRNAs
US20040137471A1 (en) 2002-09-18 2004-07-15 Timothy Vickers Efficient reduction of target RNA's by single-and double-stranded oligomeric compounds
AU2003249012A1 (en) 2002-09-30 2004-04-23 Japan As Represented By The President Of The University Of Tokyo Genes and polypeptides relating to human myeloid leukemia
AU2003304386A1 (en) 2002-10-30 2005-02-25 The Center For Blood Research, Inc. Methods for treating and preventing apoptosis-related diseases using rna interfering agents
US7521431B2 (en) 2002-11-01 2009-04-21 The Trustees Of The University Of Pennsylvania Compositions and methods for siRNA inhibition of HIF-1 alpha
JP2006505288A (en) 2002-11-04 2006-02-16 ユニバーシティー オブ マサチューセッツ Allele-specific RNA interference
US7635770B2 (en) 2002-11-14 2009-12-22 Dharmacon, Inc. siRNA targeting protein kinase N-3 (PKN-3)
US7582747B2 (en) 2002-11-14 2009-09-01 Dharmacon, Inc. siRNA targeting inner centromere protein antigens (INCENP)
US7977471B2 (en) 2002-11-14 2011-07-12 Dharmacon, Inc. siRNA targeting TNFα
US7781575B2 (en) 2002-11-14 2010-08-24 Dharmacon, Inc. siRNA targeting tumor protein 53 (p53)
US7250496B2 (en) 2002-11-14 2007-07-31 Rosetta Genomics Ltd. Bioinformatically detectable group of novel regulatory genes and uses thereof
US7612196B2 (en) 2002-11-14 2009-11-03 Dharmacon, Inc. siRNA targeting cyclin-dependent kinase inhibitor 1B (p27, Kip1) (CDKN1B)
US7592442B2 (en) 2002-11-14 2009-09-22 Dharmacon, Inc. siRNA targeting ribonucleotide reductase M2 polypeptide (RRM2 or RNR-R2)
WO2006006948A2 (en) 2002-11-14 2006-01-19 Dharmacon, Inc. METHODS AND COMPOSITIONS FOR SELECTING siRNA OF IMPROVED FUNCTIONALITY
US7951935B2 (en) 2002-11-14 2011-05-31 Dharmacon, Inc. siRNA targeting v-myc myelocytomatosis viral oncogene homolog (MYC)
US7691998B2 (en) 2002-11-14 2010-04-06 Dharmacon, Inc. siRNA targeting nucleoporin 62kDa (Nup62)
EP1560931B1 (en) 2002-11-14 2011-07-27 Dharmacon, Inc. Functional and hyperfunctional sirna
US7619081B2 (en) 2002-11-14 2009-11-17 Dharmacon, Inc. siRNA targeting coatomer protein complex, subunit beta 2 (COPB2)
WO2004046324A2 (en) 2002-11-15 2004-06-03 University Of Massachusetts Allele-targeted rna interference
US7217807B2 (en) 2002-11-26 2007-05-15 Rosetta Genomics Ltd Bioinformatically detectable group of novel HIV regulatory genes and uses thereof
AU2003302167A1 (en) 2002-12-12 2004-06-30 The Burnham Institute Conversion of apoptotic proteins
US20040248299A1 (en) * 2002-12-27 2004-12-09 Sumedha Jayasena RNA interference
WO2004070062A2 (en) * 2003-02-04 2004-08-19 Wyeth Compositions and methods for diagnosing and treating cancers
FR2835838B1 (en) * 2003-02-06 2007-11-16 Centre Nat Rech Scient OLIGONUCLEOTIDES INHIBITORS AND THEIR USE FOR SPECIFICALLY REPRESSING A GENE ENCODING A TRANSCRIPTION FACTOR
FR2835837B1 (en) * 2003-02-06 2007-03-16 Centre Nat Rech Scient INHIBITORY OLIGONUCLEOTIDES AND THEIR USE FOR SPECIFICALLY REPRESSING A GENE ENCODING A GROWTH FACTOR
WO2004076639A2 (en) 2003-02-26 2004-09-10 Wyeth Use of gene expression profiling in the diagnosis and treatment of lupus nephritis and systemic lupus erythematosus
EP1608733B1 (en) 2003-04-02 2011-12-07 Dharmacon, Inc. Modified polynucleotides for use in rna interference
WO2004094636A1 (en) 2003-04-24 2004-11-04 Galapagos Genomics N.V. Effective sirna knock-down constructs
US7399853B2 (en) 2003-04-28 2008-07-15 Isis Pharmaceuticals Modulation of glucagon receptor expression
US20080020990A1 (en) * 2003-05-30 2008-01-24 Nippon Shinyaku Co., Ltd. Oligo Double-Stranded Rna Inhibiting the Expression of Bcl-2 and Pharmaceutical Composition Containing the Same
KR20060063788A (en) * 2003-05-30 2006-06-12 니뽄 신야쿠 가부시키가이샤 Oligonucleotide Support Complex, Pharmaceutical Composition Containing the Complex
ATE485394T1 (en) 2003-06-02 2010-11-15 Univ Massachusetts METHODS AND COMPOSITIONS FOR IMPROVING THE EFFECTIVENESS AND SPECIFICITY OF FNAI
PL1633767T3 (en) 2003-06-02 2019-07-31 University Of Massachusetts Methods and compositions for controlling efficacy of rna silencing
US7750144B2 (en) 2003-06-02 2010-07-06 University Of Massachusetts Methods and compositions for enhancing the efficacy and specificity of RNA silencing
DK3604537T3 (en) 2003-06-13 2022-02-28 Alnylam Europe Ag Double-stranded ribonucleic acid with increased efficiency in an organism
US7825235B2 (en) 2003-08-18 2010-11-02 Isis Pharmaceuticals, Inc. Modulation of diacylglycerol acyltransferase 2 expression
DE10341333B4 (en) * 2003-09-08 2006-06-08 Siemens Ag Piezoelectric actuator and method for producing a piezoelectric actuator
KR100568246B1 (en) * 2003-11-19 2006-04-05 삼성전자주식회사 Computer system and its control method
US20050176045A1 (en) 2004-02-06 2005-08-11 Dharmacon, Inc. SNP discriminatory siRNA
WO2005089224A2 (en) 2004-03-12 2005-09-29 Alnylam Pharmaceuticals, Inc. iRNA AGENTS TARGETING VEGF
KR101147147B1 (en) 2004-04-01 2012-05-25 머크 샤프 앤드 돔 코포레이션 Modified polynucleotides for reducing off-target effects in rna interference
EP1747022A4 (en) 2004-04-23 2010-03-31 Univ Columbia INHIBITION OF HAIRLESS GENE PROTEIN-ASSOCIATED MRNA (NO HAIR)
EP1750775A2 (en) 2004-05-04 2007-02-14 Nastech Pharmaceutical Company Inc. Compositions and methods for enhancing delivery of nucleic acids into cells and for modifying expression of target genes in cells
EP1752536A4 (en) 2004-05-11 2008-04-16 Alphagen Co Ltd Polynucleotide causing rna interfere and method of regulating gene expression with the use of the same
US7605250B2 (en) 2004-05-12 2009-10-20 Dharmacon, Inc. siRNA targeting cAMP-specific phosphodiesterase 4D
JP2006013252A (en) * 2004-06-28 2006-01-12 Hitachi Cable Ltd Laser diode control method, control circuit, and optical transmitter
PT1799269T (en) 2004-09-28 2016-10-04 Quark Pharmaceuticals Inc Oligoribonucleotides and methods of use thereof for treatment of alopecia, acute renal failure and other diseases
AU2005306533B2 (en) 2004-11-17 2012-05-31 Arbutus Biopharma Corporation siRNA silencing of apolipoprotein B
AU2006235489A1 (en) 2005-04-12 2006-10-19 Intradigm Corporation Composition and methods of RNAi therapeutics for treatment of cancer and other neovascularization diseases
US20060286575A1 (en) 2005-04-16 2006-12-21 Cylene Pharmaceuticals, Inc. MCL-1 quadruplex nucleic acids and uses thereof
US7825099B2 (en) 2006-01-20 2010-11-02 Quark Pharmaceuticals, Inc. Treatment or prevention of oto-pathologies by inhibition of pro-apoptotic genes
US7910566B2 (en) 2006-03-09 2011-03-22 Quark Pharmaceuticals Inc. Prevention and treatment of acute renal failure and other kidney diseases by inhibition of p53 by siRNA
CA2650416A1 (en) 2006-05-19 2007-11-29 Alcon Research, Ltd. Rnai-mediated inhibition of tumor necrosis factor .alpha.-related conditions
US8523707B2 (en) * 2006-05-31 2013-09-03 Bridgestone Sports Co., Ltd. Multi-piece solid golf ball
US8138160B2 (en) 2006-08-03 2012-03-20 Warsaw Orthopedic, Inc. Reagents, methods and systems to suppress pro-inflammatory cytokines
CN101640467B (en) 2008-07-28 2012-05-30 鸿富锦精密工业（深圳）有限公司 Shrapnel and Voice Coil Motors

Patent Citations (100)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US647526A (en) * 1899-06-26 1900-04-17 William Allen Runyan Freight-car door.
US3719760A (en) * 1968-01-29 1973-03-06 Bayer Ag N-trityl-imidazolium salts as a fungicide
US3811449A (en) * 1972-03-08 1974-05-21 Becton Dickinson Co Dilating apparatus and method
US4401433A (en) * 1980-06-13 1983-08-30 Luther Ronald B Apparatus for advancing oversized catheter through cannula, and the like
US4449532A (en) * 1980-07-08 1984-05-22 Karl Storz Dilator to facilitate endoscope insertion into the body
US4369790A (en) * 1981-03-05 1983-01-25 Mccarthy John M Catheter
US4350151A (en) * 1981-03-12 1982-09-21 Lone Star Medical Products, Inc. Expanding dilator
US4451256A (en) * 1981-05-06 1984-05-29 Intermedicat Gmbh Catheter set
US4601710B1 (en) * 1983-08-24 1998-05-05 United States Surgical Corp Trocar assembly
US4601710A (en) * 1983-08-24 1986-07-22 Endotherapeutics Corporation Trocar assembly
US4573448A (en) * 1983-10-05 1986-03-04 Pilling Co. Method for decompressing herniated intervertebral discs
US4686984A (en) * 1984-03-15 1987-08-18 Richard Wolf Gmbh Catheter for widening a puncture channel
US4802479A (en) * 1986-10-31 1989-02-07 C. R. Bard, Inc. Hand-held instrument for implanting, dispensing, and inflating an inflatable membrane
US4981482A (en) * 1987-08-20 1991-01-01 Kazuo Ichikawa Device for forming an inserting hole for an endoscope
US4862891A (en) * 1988-03-14 1989-09-05 Canyon Medical Products Device for sequential percutaneous dilation
US4994027A (en) * 1988-06-08 1991-02-19 Farrell Edward M Percutaneous femoral bypass system
US5224952A (en) * 1988-07-06 1993-07-06 Ethicon, Inc. Safety trocar
US5613950A (en) * 1988-07-22 1997-03-25 Yoon; Inbae Multifunctional manipulating instrument for various surgical procedures
US5782800A (en) * 1988-07-22 1998-07-21 Yoon; Inbae Expandable multifunctional manipulating instruments for various medical procedures and methods therefor
US5002557A (en) * 1989-04-06 1991-03-26 Hasson Harrith M Laparoscopic cannula
US5176697A (en) * 1989-04-06 1993-01-05 Hasson Harrith M Laparoscopic cannula
US5114407A (en) * 1990-08-30 1992-05-19 Ethicon, Inc. Safety mechanism for trocar
US5188118A (en) * 1990-11-07 1993-02-23 Terwilliger Richard A Automatic biopsy instrument with independently actuated stylet and cannula
US5324261A (en) * 1991-01-04 1994-06-28 Medtronic, Inc. Drug delivery balloon catheter with line of weakness
US5342382A (en) * 1991-01-15 1994-08-30 Ethicon, Inc. Surgical trocar
US5176651A (en) * 1991-04-01 1993-01-05 Dexide, Inc. Combination surgical trocar housing and selective reducer sleeve assembly
US5486190A (en) * 1991-04-30 1996-01-23 United States Surgical Corporation Safety trocar
US5241972A (en) * 1991-05-03 1993-09-07 Meditron Devices, Inc. Method for debulking tissue to remove pressure on a nerve
US5183464A (en) * 1991-05-17 1993-02-02 Interventional Thermodynamics, Inc. Radially expandable dilator
US6197041B1 (en) * 1991-06-26 2001-03-06 United States Surgical Corporation Trocar
US5195506A (en) * 1991-10-18 1993-03-23 Life Medical Products, Inc. Surgical retractor for puncture operation
US5280782A (en) * 1991-11-15 1994-01-25 Wilk Peter J Variable length laparoscopic retractor and associated method of use
US5810866A (en) * 1991-11-27 1998-09-22 Yoon; Inbae Automatic retractable safety penetrating instrument for portal sleeve introduction
US5713870A (en) * 1991-11-27 1998-02-03 Yoon; Inbae Retractable safety penetrating instrument with laterally extendable spring strip
US6033406A (en) * 1992-03-17 2000-03-07 Sdgi Holdings, Inc. Method for subcutaneous suprafascial pedicular internal fixation
US5728097A (en) * 1992-03-17 1998-03-17 Sdgi Holding, Inc. Method for subcutaneous suprafascial internal fixation
US5290243A (en) * 1992-07-16 1994-03-01 Technalytics, Inc. Trocar system
US5312417A (en) * 1992-07-29 1994-05-17 Wilk Peter J Laparoscopic cannula assembly and associated method
US20040059350A1 (en) * 1992-09-04 2004-03-25 Scimed Life Systems, Inc. Suturing instruments and methods of use
US6364897B1 (en) * 1993-02-04 2002-04-02 Peter M. Bonutti Method and apparatus for positioning a suture anchor
US5752969A (en) * 1993-06-17 1998-05-19 Sofamor S.N.C. Instrument for the surgical treatment of an intervertebral disc by the anterior route
US5407430A (en) * 1994-03-21 1995-04-18 Peters; Michael J. Intravenous catheter
US5512037A (en) * 1994-05-12 1996-04-30 United States Surgical Corporation Percutaneous surgical retractor
US5505710A (en) * 1994-08-22 1996-04-09 C. R. Bard, Inc. Telescoping probe
US5647857A (en) * 1995-03-16 1997-07-15 Endotex Interventional Systems, Inc. Protective intraluminal sheath
US5624447A (en) * 1995-03-20 1997-04-29 Othy, Inc. Surgical tool guide and entry hole positioner
US6206922B1 (en) * 1995-03-27 2001-03-27 Sdgi Holdings, Inc. Methods and instruments for interbody fusion
US6695851B2 (en) * 1995-03-27 2004-02-24 Sdgi Holdings, Inc. Methods and instruments for interbody fusion
US5776156A (en) * 1995-09-05 1998-07-07 United States Surgical Corporation Endoscopic cutting instrument
US6213957B1 (en) * 1995-09-08 2001-04-10 United States Surgical Corporation Apparatus and method for removing tissue
US5772678A (en) * 1995-10-20 1998-06-30 Inlet Medical, Inc. Retractable disposable tip reusable trocar obturator
US5743881A (en) * 1995-11-03 1998-04-28 Aptec Medical Corporation Laparoscopic surgical instrument and method of using same
US5707359A (en) * 1995-11-14 1998-01-13 Bufalini; Bruno Expanding trocar assembly
US6048309A (en) * 1996-03-04 2000-04-11 Heartport, Inc. Soft tissue retractor and delivery device therefor
US5810721A (en) * 1996-03-04 1998-09-22 Heartport, Inc. Soft tissue retractor and method for providing surgical access
US6217509B1 (en) * 1996-03-22 2001-04-17 Sdgi Holdings, Inc. Devices and methods for percutaneous surgery
US6520907B1 (en) * 1996-03-22 2003-02-18 Sdgi Holdings, Inc. Methods for accessing the spinal column
US5902231A (en) * 1996-03-22 1999-05-11 Sdgi Holdings, Inc. Devices and methods for percutaneous surgery
US5792044A (en) * 1996-03-22 1998-08-11 Danek Medical, Inc. Devices and methods for percutaneous surgery
US6679833B2 (en) * 1996-03-22 2004-01-20 Sdgi Holdings, Inc. Devices and methods for percutaneous surgery
US6264676B1 (en) * 1996-11-08 2001-07-24 Scimed Life Systems, Inc. Protective sheath for transvaginal anchor implantation devices
US6053935A (en) * 1996-11-08 2000-04-25 Boston Scientific Corporation Transvaginal anchor implantation device
US6440154B2 (en) * 1996-11-08 2002-08-27 Scimed Life Systems, Inc. Protective sheath for transvaginal anchor implantation device
US6348053B1 (en) * 1996-11-12 2002-02-19 Triage Medical, Inc. Bone fixation device
US6447540B1 (en) * 1996-11-15 2002-09-10 Cook Incorporated Stent deployment device including splittable sleeve containing the stent
US6228058B1 (en) * 1997-04-03 2001-05-08 Core Dynamics, Inc. Sleeve trocar with penetration indicator
US6293952B1 (en) * 1997-07-31 2001-09-25 Circon Corporation Medical instrument system for piercing through tissue
US20040049223A1 (en) * 1997-10-01 2004-03-11 Scimed Life Systems, Inc. Dilation systems and related methods
US20010012950A1 (en) * 1997-10-01 2001-08-09 Srinivas Nishtala Dilation systems and related methods
US6030364A (en) * 1997-10-03 2000-02-29 Boston Scientific Corporation Apparatus and method for percutaneous placement of gastro-intestinal tubes
US6206826B1 (en) * 1997-12-18 2001-03-27 Sdgi Holdings, Inc. Devices and methods for percutaneous surgery
US6428541B1 (en) * 1998-04-09 2002-08-06 Sdgi Holdings, Inc. Method and instrumentation for vertebral interbody fusion
US6447527B1 (en) * 1998-04-23 2002-09-10 Ronald J. Thompson Apparatus and methods for the penetration of tissue
US20020001476A1 (en) * 1998-06-26 2002-01-03 Tomoyuki Nagamine Image forming apparatus
US6293909B1 (en) * 1998-08-07 2001-09-25 Scimed Life Systems, Inc. Device and method of using a surgical assembly with mesh sheath
US6689152B2 (en) * 1998-09-09 2004-02-10 Edwards Lifesciences Corp. Introducer/dilator with balloon protection and methods of use
US6117174A (en) * 1998-09-16 2000-09-12 Nolan; Wesley A. Spinal implant device
US5957902A (en) * 1998-09-28 1999-09-28 Teves; Leonides Y. Surgical tool for enlarging puncture opening made by trocar
US6743166B2 (en) * 1999-02-12 2004-06-01 Karl Storz Gmbh & Co. Kg Apparatus for introducing an intubation tube into the trachea
US6607530B1 (en) * 1999-05-10 2003-08-19 Highgate Orthopedics, Inc. Systems and methods for spinal fixation
US6200322B1 (en) * 1999-08-13 2001-03-13 Sdgi Holdings, Inc. Minimal exposure posterior spinal interbody instrumentation and technique
US6428556B1 (en) * 1999-08-25 2002-08-06 Origin Medsystems, Inc. Longitudinal dilator and method
US6723096B1 (en) * 1999-08-26 2004-04-20 Sdgi Holdings, Inc. Devices and methods for implanting fusion cages
US6582437B2 (en) * 1999-08-26 2003-06-24 Sdgi Holdings, Inc. Devices and methods for implanting fusion cages
US6562046B2 (en) * 1999-11-23 2003-05-13 Sdgi Holdings, Inc. Screw delivery system and method
US6582441B1 (en) * 2000-02-24 2003-06-24 Advanced Bionics Corporation Surgical insertion tool
US6562049B1 (en) * 2000-03-01 2003-05-13 Cook Vascular Incorporated Medical introducer apparatus
US6592553B2 (en) * 2000-07-05 2003-07-15 Cardiac Pacemakers, Inc. Introducer assembly and method therefor
US7172612B2 (en) * 2000-12-12 2007-02-06 Olympus Corporation Trocar and trocar system
US20020087152A1 (en) * 2001-01-04 2002-07-04 Endocare, Inc. Systems and methods for delivering a probe into tissue
US6511481B2 (en) * 2001-03-30 2003-01-28 Triage Medical, Inc. Method and apparatus for fixation of proximal femoral fractures
US6746451B2 (en) * 2001-06-01 2004-06-08 Lance M. Middleton Tissue cavitation device and method
US6589240B2 (en) * 2001-08-28 2003-07-08 Rex Medical, L.P. Tissue biopsy apparatus with collapsible cutter
US20030083688A1 (en) * 2001-10-30 2003-05-01 Simonson Robert E. Configured and sized cannula
US6685706B2 (en) * 2001-11-19 2004-02-03 Triage Medical, Inc. Proximal anchors for bone fixation system
US7025746B2 (en) * 2001-12-26 2006-04-11 Yale University Vascular access device
US20040019359A1 (en) * 2002-07-24 2004-01-29 Worley Seth J. Telescopic introducer with a compound curvature for inducing alignment and method of using the same
US20040059339A1 (en) * 2002-09-19 2004-03-25 Roehm Thomas E. Oval dilator and retractor set and method
US20040147877A1 (en) * 2003-01-27 2004-07-29 Heuser Richard R Catheter introducer system
US20040158258A1 (en) * 2003-02-12 2004-08-12 Bonati Alfred O. Method for removing orthopaedic hardware

Cited By (223)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11051862B2 (en) 2001-11-03 2021-07-06 DePuy Synthes Products, Inc. Device for straightening and stabilizing the vertebral column
USD666293S1 (en) * 2002-06-26 2012-08-28 Nuvasive, Inc. Dilator
USD666292S1 (en) * 2002-06-26 2012-08-28 Nuvasive, Inc. Dilator
USD666294S1 (en) * 2002-06-26 2012-08-28 Nuvasive, Inc. Dilator
US9993349B2 (en) 2002-06-27 2018-06-12 DePuy Synthes Products, Inc. Intervertebral disc
US9713486B2 (en) 2002-07-19 2017-07-25 DePuy Synthes Products, Inc. Method and apparatus for spinal fixation
US8945190B2 (en) 2002-07-19 2015-02-03 Interventional Spine, Inc. Method and apparatus for spinal fixation
US8109977B2 (en) 2002-07-19 2012-02-07 Interventional Spine, Inc. Method and apparatus for spinal fixation
US20060004398A1 (en) * 2004-07-02 2006-01-05 Binder Lawrence J Jr Sequential dilator system
US20060069384A1 (en) * 2004-09-21 2006-03-30 Daniel Wallaker Instrument for use in a medical simulator
US8206157B2 (en) * 2004-09-21 2012-06-26 Keymed (Medical & Industrial Equipment) Limited Instrument for use in a medical simulator
US20070129747A1 (en) * 2005-11-14 2007-06-07 Scapa Flow, Llc Medical dilator system or dilator device
US8066730B2 (en) * 2005-11-14 2011-11-29 Scapa Flow, Llc Medical dilator system or dilator device
US9101411B2 (en) 2006-04-21 2015-08-11 Interventional Spine, Inc. Method and apparatus for spinal fixation
US20110218575A1 (en) * 2006-04-21 2011-09-08 Interventional Spine, Inc. Method and apparatus for spinal fixation
US7938832B2 (en) 2006-04-21 2011-05-10 Interventional Spine, Inc. Method and apparatus for spinal fixation
US20080097436A1 (en) * 2006-04-21 2008-04-24 Culbert Brad S Method and apparatus for spinal fixation
US8430813B2 (en) 2006-05-26 2013-04-30 Depuy Spine, Inc. Illuminated surgical access system including a surgical access device and integrated light emitter
USD648021S1 (en) 2006-11-14 2011-11-01 Scapa Flow, Llc Medical dilator
USD631962S1 (en) 2006-11-14 2011-02-01 Scapa Flow, Llc Medical dilator
US11273050B2 (en) 2006-12-07 2022-03-15 DePuy Synthes Products, Inc. Intervertebral implant
US11642229B2 (en) 2006-12-07 2023-05-09 DePuy Synthes Products, Inc. Intervertebral implant
US10583015B2 (en) 2006-12-07 2020-03-10 DePuy Synthes Products, Inc. Intervertebral implant
US11660206B2 (en) 2006-12-07 2023-05-30 DePuy Synthes Products, Inc. Intervertebral implant
US11712345B2 (en) 2006-12-07 2023-08-01 DePuy Synthes Products, Inc. Intervertebral implant
US11432942B2 (en) 2006-12-07 2022-09-06 DePuy Synthes Products, Inc. Intervertebral implant
US10398566B2 (en) 2006-12-07 2019-09-03 DePuy Synthes Products, Inc. Intervertebral implant
US11497618B2 (en) 2006-12-07 2022-11-15 DePuy Synthes Products, Inc. Intervertebral implant
US10390963B2 (en) 2006-12-07 2019-08-27 DePuy Synthes Products, Inc. Intervertebral implant
US11045324B2 (en) 2006-12-08 2021-06-29 DePuy Synthes Products, Inc. Method of implanting a curable implant material
US8425525B2 (en) * 2007-05-23 2013-04-23 Rainer Baumgart Instrument set for minimally invasive preparation for bone nailing
US20080294172A1 (en) * 2007-05-23 2008-11-27 Rainer Baumgart Instrument set for minimally invasive preparation for bone nailing
US10973652B2 (en) 2007-06-26 2021-04-13 DePuy Synthes Products, Inc. Highly lordosed fusion cage
US9839530B2 (en) 2007-06-26 2017-12-12 DePuy Synthes Products, Inc. Highly lordosed fusion cage
US11622868B2 (en) 2007-06-26 2023-04-11 DePuy Synthes Products, Inc. Highly lordosed fusion cage
US8043343B2 (en) 2007-06-28 2011-10-25 Zimmer Spine, Inc. Stabilization system and method
US9974533B2 (en) 2007-10-05 2018-05-22 DePuy Synthes Products, Inc. Dilation system and method of using the same
US11737743B2 (en) 2007-10-05 2023-08-29 DePuy Synthes Products, Inc. Dilation system and method of using the same
US9387009B2 (en) 2007-10-05 2016-07-12 DePuy Synthes Products, Inc. Dilation system and method of using the same
US10925594B2 (en) 2007-10-05 2021-02-23 DePuy Synthes Products, Inc. Dilation system and method of using the same
US10194895B2 (en) 2007-10-05 2019-02-05 DePuy Synhes Products, Inc. Dilation system and method of using the same
US9737290B2 (en) 2007-10-05 2017-08-22 DePuy Synthes Products, Inc. Dilation system and method of using the same
US11737881B2 (en) 2008-01-17 2023-08-29 DePuy Synthes Products, Inc. Expandable intervertebral implant and associated method of manufacturing the same
US10449058B2 (en) 2008-01-17 2019-10-22 DePuy Synthes Products, Inc. Expandable intervertebral implant and associated method of manufacturing the same
US10433977B2 (en) 2008-01-17 2019-10-08 DePuy Synthes Products, Inc. Expandable intervertebral implant and associated method of manufacturing the same
US11701234B2 (en) 2008-04-05 2023-07-18 DePuy Synthes Products, Inc. Expandable intervertebral implant
US12023255B2 (en) 2008-04-05 2024-07-02 DePuy Synthes Products, Inc. Expandable inter vertebral implant
US10449056B2 (en) 2008-04-05 2019-10-22 DePuy Synthes Products, Inc. Expandable intervertebral implant
US11602438B2 (en) 2008-04-05 2023-03-14 DePuy Synthes Products, Inc. Expandable intervertebral implant
US11617655B2 (en) 2008-04-05 2023-04-04 DePuy Synthes Products, Inc. Expandable intervertebral implant
US9993350B2 (en) 2008-04-05 2018-06-12 DePuy Synthes Products, Inc. Expandable intervertebral implant
US12011361B2 (en) 2008-04-05 2024-06-18 DePuy Synthes Products, Inc. Expandable intervertebral implant
US11712342B2 (en) 2008-04-05 2023-08-01 DePuy Synthes Products, Inc. Expandable intervertebral implant
US11712341B2 (en) 2008-04-05 2023-08-01 DePuy Synthes Products, Inc. Expandable intervertebral implant
US11707359B2 (en) 2008-04-05 2023-07-25 DePuy Synthes Products, Inc. Expandable intervertebral implant
US9931223B2 (en) 2008-04-05 2018-04-03 DePuy Synthes Products, Inc. Expandable intervertebral implant
WO2009147527A2 (en) 2008-05-26 2009-12-10 Rudolf Morgernstern Lopez Intervertebral implant and installation tool
US11612491B2 (en) 2009-03-30 2023-03-28 DePuy Synthes Products, Inc. Zero profile spinal fusion cage
US12097124B2 (en) 2009-03-30 2024-09-24 DePuy Synthes Products, Inc. Zero profile spinal fusion cage
US20110004222A1 (en) * 2009-04-07 2011-01-06 Lutz Biedermann Tool for Use with a Bone Anchor, in Particular for Spinal Surgery
US9149308B2 (en) * 2009-04-07 2015-10-06 Biedermann Technologies Gmbh & Co. Kg Tool for use with a bone anchor, in particular for spinal surgery
US11925723B2 (en) 2009-08-27 2024-03-12 Silver Bullet Therapeutics, Inc. Bone implant and systems and coatings for the controllable release of antimicrobial metal ions
US10265435B2 (en) 2009-08-27 2019-04-23 Silver Bullet Therapeutics, Inc. Bone implant and systems and coatings for the controllable release of antimicrobial metal ions
US10004548B2 (en) 2009-08-27 2018-06-26 Silver Bullet Therapeutics, Inc. Bone implants for the treatment of infection
US11224471B2 (en) 2009-08-27 2022-01-18 Silver Bullet Therapeutics, Inc. Bone implants for the treatment of infection
US9248254B2 (en) 2009-08-27 2016-02-02 Silver Bullet Therapeutics, Inc. Bone implants for the treatment of infection
US8221396B2 (en) 2009-08-27 2012-07-17 Silver Bullet Therapeutics, Inc. Bone implants for the treatment of infection
US9889284B2 (en) 2009-08-27 2018-02-13 Silver Bullet Therapeutics, Inc. Bone implant and systems that controllably releases silver
US11020508B2 (en) 2009-08-27 2021-06-01 Silver Bullet Therapeutics, Inc. Bone implant and systems and coatings for the controllable release of antimicrobial metal ions
US10368929B2 (en) 2009-08-27 2019-08-06 Silver Bullet Therapeutics, Inc. Bone implants for the treatment of infection
US10500062B2 (en) 2009-12-10 2019-12-10 DePuy Synthes Products, Inc. Bellows-like expandable interbody fusion cage
US11607321B2 (en) 2009-12-10 2023-03-21 DePuy Synthes Products, Inc. Bellows-like expandable interbody fusion cage
US20110144687A1 (en) * 2009-12-10 2011-06-16 Kleiner Jeffrey Lateral Based Retractor System
US10966840B2 (en) 2010-06-24 2021-04-06 DePuy Synthes Products, Inc. Enhanced cage insertion assembly
US12318304B2 (en) 2010-06-24 2025-06-03 DePuy Synthes Products, Inc. Lateral spondylolisthesis reduction cage
US11872139B2 (en) 2010-06-24 2024-01-16 DePuy Synthes Products, Inc. Enhanced cage insertion assembly
US11911287B2 (en) 2010-06-24 2024-02-27 DePuy Synthes Products, Inc. Lateral spondylolisthesis reduction cage
US9895236B2 (en) 2010-06-24 2018-02-20 DePuy Synthes Products, Inc. Enhanced cage insertion assembly
US10548741B2 (en) 2010-06-29 2020-02-04 DePuy Synthes Products, Inc. Distractible intervertebral implant
US11654033B2 (en) 2010-06-29 2023-05-23 DePuy Synthes Products, Inc. Distractible intervertebral implant
US11452607B2 (en) 2010-10-11 2022-09-27 DePuy Synthes Products, Inc. Expandable interspinous process spacer implant
US9108051B2 (en) 2010-11-12 2015-08-18 Silver Bullet Therapeutics, Inc. Bone implant and systems that controllably releases silver
US9789298B2 (en) 2010-11-12 2017-10-17 Silver Bullet Therapeutics, Inc. Bone implant and systems that controllably releases silver
US8771323B2 (en) 2010-11-12 2014-07-08 Silver Bullet Therapeutics, Inc. Bone implant and systems that controllably releases silver
WO2012102842A1 (en) * 2011-01-28 2012-08-02 Laser Spine Surgical Center, LLC Foraminoplasty device
US10111759B2 (en) 2011-03-10 2018-10-30 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US10744004B2 (en) 2011-03-10 2020-08-18 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US9492194B2 (en) * 2011-03-10 2016-11-15 Interventional Spine, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US11547443B2 (en) 2011-03-10 2023-01-10 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US10729462B2 (en) 2011-03-10 2020-08-04 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US10736661B2 (en) 2011-03-10 2020-08-11 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US10743915B2 (en) 2011-03-10 2020-08-18 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US10743914B2 (en) 2011-03-10 2020-08-18 DePuy Snythes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US10743913B2 (en) 2011-03-10 2020-08-18 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US11547442B2 (en) * 2011-03-10 2023-01-10 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US9486149B2 (en) * 2011-03-10 2016-11-08 Interventional Spine, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US20150094610A1 (en) * 2011-03-10 2015-04-02 Interventional Spine, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US11484418B2 (en) 2011-03-10 2022-11-01 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
AU2012225473B2 (en) * 2011-03-10 2016-07-21 Interventional Spine, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US11484419B2 (en) 2011-03-10 2022-11-01 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US11484420B2 (en) 2011-03-10 2022-11-01 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US20150112398A1 (en) * 2011-03-10 2015-04-23 Interventional Spine, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US10182842B2 (en) 2011-03-10 2019-01-22 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
AU2016247198B2 (en) * 2011-03-10 2019-04-04 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US11234736B2 (en) 2011-10-27 2022-02-01 DePuy Synthes Products, Inc. Method and devices for a sub-splenius/supra-levator scapulae surgical access technique
US11278323B2 (en) 2011-10-27 2022-03-22 DePuy Synthes Products, Inc. Method and devices for a sub-splenius/supra-levator scapulae surgical access technique
US11241255B2 (en) 2011-10-27 2022-02-08 DePuy Synthes Products, Inc. Method and devices for a sub-splenius/supra-levator scapulae surgical access technique
US11134987B2 (en) 2011-10-27 2021-10-05 DePuy Synthes Products, Inc. Method and devices for a sub-splenius/supra-levator scapulae surgical access technique
US11937797B2 (en) 2011-10-27 2024-03-26 DePuy Synthes Products, Inc. Method and devices for a sub-splenius/supra-levator scapulae surgical access technique
US11911017B2 (en) 2011-10-27 2024-02-27 DePuy Synthes Products, Inc. Method and devices for a sub-splenius/supra-levator scapulae surgical access technique
US11660082B2 (en) 2011-11-01 2023-05-30 DePuy Synthes Products, Inc. Dilation system
USRE48534E1 (en) 2012-04-16 2021-04-27 DePuy Synthes Products, Inc. Detachable dilator blade
US10058433B2 (en) 2012-07-26 2018-08-28 DePuy Synthes Products, Inc. Expandable implant
US9883951B2 (en) 2012-08-30 2018-02-06 Interventional Spine, Inc. Artificial disc
US11219439B2 (en) 2012-09-26 2022-01-11 DePuy Synthes Products, Inc. NIR/RED light for lateral neuroprotection
US11559295B2 (en) 2012-09-26 2023-01-24 DePuy Synthes Products, Inc. NIR/red light for lateral neuroprotection
US20140171946A1 (en) * 2012-12-14 2014-06-19 Warsaw Orthopedic, Inc. Surgical instrument and method
US9198674B2 (en) * 2012-12-14 2015-12-01 Warsaw Orthopedic, Inc. Surgical instrument and method
USRE49973E1 (en) 2013-02-28 2024-05-21 DePuy Synthes Products, Inc. Expandable intervertebral implant, system, kit and method
US11497619B2 (en) 2013-03-07 2022-11-15 DePuy Synthes Products, Inc. Intervertebral implant
US11850164B2 (en) 2013-03-07 2023-12-26 DePuy Synthes Products, Inc. Intervertebral implant
US9522070B2 (en) 2013-03-07 2016-12-20 Interventional Spine, Inc. Intervertebral implant
US10413422B2 (en) 2013-03-07 2019-09-17 DePuy Synthes Products, Inc. Intervertebral implant
US11759329B2 (en) 2013-03-11 2023-09-19 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US10813772B2 (en) 2013-03-11 2020-10-27 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US9855058B2 (en) 2013-03-11 2018-01-02 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US10898342B2 (en) 2013-03-11 2021-01-26 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US12004960B2 (en) 2013-03-11 2024-06-11 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US10918495B2 (en) 2013-03-11 2021-02-16 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US10898341B2 (en) 2013-03-11 2021-01-26 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US9277928B2 (en) 2013-03-11 2016-03-08 Interventional Spine, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US12285342B2 (en) 2013-03-14 2025-04-29 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US11590002B2 (en) 2013-03-14 2023-02-28 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
USRE49994E1 (en) 2013-03-14 2024-06-04 Spinal Elements, Inc. Spinal fusion implants and devices and methods for deploying such implants
US10537443B2 (en) 2013-03-14 2020-01-21 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US9993353B2 (en) 2013-03-14 2018-06-12 DePuy Synthes Products, Inc. Method and apparatus for minimally invasive insertion of intervertebral implants
US11006991B2 (en) 2013-07-03 2021-05-18 DePuy Synthes Products, Inc. Method and apparatus for sacroiliac joint fixation
US9522028B2 (en) 2013-07-03 2016-12-20 Interventional Spine, Inc. Method and apparatus for sacroiliac joint fixation
US10166056B2 (en) 2013-07-03 2019-01-01 DePuy Synthes Products, Inc. Method and apparatus for sacroiliac joint fixation
US9821094B2 (en) 2014-06-11 2017-11-21 Silver Bullet Therapeutics, Inc. Coatings for the controllable release of antimicrobial metal ions
US9452242B2 (en) 2014-06-11 2016-09-27 Silver Bullet Therapeutics, Inc. Enhancement of antimicrobial silver, silver coatings, or silver platings
US8927004B1 (en) 2014-06-11 2015-01-06 Silver Bullet Therapeutics, Inc. Bioabsorbable substrates and systems that controllably release antimicrobial metal ions
US9114197B1 (en) 2014-06-11 2015-08-25 Silver Bullett Therapeutics, Inc. Coatings for the controllable release of antimicrobial metal ions
US8999367B1 (en) 2014-06-11 2015-04-07 Silver Bullet Therapeutics, Inc. Bioabsorbable substrates and systems that controllably release antimicrobial metal ions
US11224453B2 (en) 2014-07-08 2022-01-18 Spinal Elements, Inc. Apparatus and methods for disrupting intervertebral disc tissue
US12053196B2 (en) 2014-07-08 2024-08-06 Spinal Elements, Inc. Apparatus and methods for disrupting inter vertebral disc tissue
US9980737B2 (en) 2014-08-04 2018-05-29 Medos International Sarl Flexible transport auger
US10863994B2 (en) 2014-08-04 2020-12-15 Medos International Sàrl Flexible transport auger
US11712252B2 (en) 2014-08-04 2023-08-01 Medos International Sarl Flexible transport auger
US9924979B2 (en) 2014-09-09 2018-03-27 Medos International Sarl Proximal-end securement of a minimally invasive working channel
US11213196B2 (en) 2014-09-09 2022-01-04 Medos International Sarl Proximal-end securement of a minimally invasive working channel
US10786330B2 (en) 2014-09-09 2020-09-29 Medos International Sarl Proximal-end securement of a minimally invasive working channel
US10264959B2 (en) 2014-09-09 2019-04-23 Medos International Sarl Proximal-end securement of a minimally invasive working channel
US10111712B2 (en) 2014-09-09 2018-10-30 Medos International Sarl Proximal-end securement of a minimally invasive working channel
US12121456B2 (en) 2015-02-06 2024-10-22 Spinal Elements, Inc. Graft material injector system and method
US11564811B2 (en) 2015-02-06 2023-01-31 Spinal Elements, Inc. Graft material injector system and method
US11426290B2 (en) 2015-03-06 2022-08-30 DePuy Synthes Products, Inc. Expandable intervertebral implant, system, kit and method
US12042158B2 (en) 2015-03-31 2024-07-23 Medos International Sarl Percutaneous disc clearing device
US12343021B2 (en) 2015-03-31 2025-07-01 Medos International Sàrl Percutaneous disc clearing device
US10786264B2 (en) 2015-03-31 2020-09-29 Medos International Sarl Percutaneous disc clearing device
US11464523B2 (en) 2015-03-31 2022-10-11 Medos International Sarl Percutaneous disc clearing device
US9833338B2 (en) * 2015-06-30 2017-12-05 Expanding Orthopedics Inc. Tool for intervertebral cage
US20170000627A1 (en) * 2015-06-30 2017-01-05 Mark M Levy Tool for intervertebral cage
US9913727B2 (en) 2015-07-02 2018-03-13 Medos International Sarl Expandable implant
US11793546B2 (en) 2015-09-04 2023-10-24 Medos International Sarl Surgical visualization systems and related methods
US12383302B2 (en) 2015-09-04 2025-08-12 Medos International Sàrl Surgical visualization systems and related methods
US11331090B2 (en) 2015-09-04 2022-05-17 Medos International Sarl Surgical visualization systems and related methods
US12150636B2 (en) 2015-09-04 2024-11-26 Medos International Sárl Surgical instrument connectors and related methods
US11672562B2 (en) 2015-09-04 2023-06-13 Medos International Sarl Multi-shield spinal access system
US12402909B2 (en) 2015-09-04 2025-09-02 Medos International Sàrl Multi-shield spinal access system
US11344190B2 (en) 2015-09-04 2022-05-31 Medos International Sarl Surgical visualization systems and related methods
US10869659B2 (en) 2015-09-04 2020-12-22 Medos International Sarl Surgical instrument connectors and related methods
US11000312B2 (en) 2015-09-04 2021-05-11 Medos International Sarl Multi-shield spinal access system
US11712264B2 (en) 2015-09-04 2023-08-01 Medos International Sarl Multi-shield spinal access system
US11883064B2 (en) 2015-09-04 2024-01-30 Medos International Sarl Multi-shield spinal access system
US10987129B2 (en) 2015-09-04 2021-04-27 Medos International Sarl Multi-shield spinal access system
US10874425B2 (en) 2015-09-04 2020-12-29 Medos International Sarl Multi-shield spinal access system
US10779810B2 (en) 2015-09-04 2020-09-22 Medos International Sarl Devices and methods for surgical retraction
US11744447B2 (en) 2015-09-04 2023-09-05 Medos International Surgical visualization systems and related methods
US12193704B2 (en) 2015-09-04 2025-01-14 Medos International Sàrl Multi-shield spinal access system
US11439380B2 (en) 2015-09-04 2022-09-13 Medos International Sarl Surgical instrument connectors and related methods
US11559328B2 (en) 2015-09-04 2023-01-24 Medos International Sarl Multi-shield spinal access system
US10758220B2 (en) 2015-09-04 2020-09-01 Medos International Sarl Devices and methods for providing surgical access
US11950766B2 (en) 2015-09-04 2024-04-09 Medos International Sàrl Surgical visualization systems and related methods
US11801070B2 (en) 2015-09-04 2023-10-31 Medos International Sarl Surgical access port stabilization
US11806043B2 (en) 2015-09-04 2023-11-07 Medos International Sarl Devices and methods for providing surgical access
US10682130B2 (en) 2015-09-04 2020-06-16 Medos International Sarl Surgical access port stabilization
US10299838B2 (en) 2016-02-05 2019-05-28 Medos International Sarl Method and instruments for interbody fusion and posterior fixation through a single incision
US12144527B2 (en) 2016-02-05 2024-11-19 Medos International Sarl Method and instruments for interbody fusion and posterior fixation through a single incision
US11020153B2 (en) 2016-02-05 2021-06-01 Medos International Sarl Method and instruments for interbody fusion and posterior fixation through a single incision
US11596523B2 (en) 2016-06-28 2023-03-07 Eit Emerging Implant Technologies Gmbh Expandable and angularly adjustable articulating intervertebral cages
US11596522B2 (en) 2016-06-28 2023-03-07 Eit Emerging Implant Technologies Gmbh Expandable and angularly adjustable intervertebral cages with articulating joint
US12390343B2 (en) 2016-06-28 2025-08-19 Eit Emerging Implant Technologies Gmbh Expandable, angularly adjustable intervertebral cages
US11510788B2 (en) 2016-06-28 2022-11-29 Eit Emerging Implant Technologies Gmbh Expandable, angularly adjustable intervertebral cages
US10537436B2 (en) 2016-11-01 2020-01-21 DePuy Synthes Products, Inc. Curved expandable cage
US10888433B2 (en) 2016-12-14 2021-01-12 DePuy Synthes Products, Inc. Intervertebral implant inserter and related methods
US20180271574A1 (en) * 2017-03-22 2018-09-27 Benvenue Medical, Inc. Minimal Impact Access System To Disc Space
US10758286B2 (en) * 2017-03-22 2020-09-01 Benvenue Medical, Inc. Minimal impact access system to disc space
US11771483B2 (en) 2017-03-22 2023-10-03 Spinal Elements, Inc. Minimal impact access system to disc space
US11446155B2 (en) 2017-05-08 2022-09-20 Medos International Sarl Expandable cage
US10398563B2 (en) 2017-05-08 2019-09-03 Medos International Sarl Expandable cage
US11344424B2 (en) 2017-06-14 2022-05-31 Medos International Sarl Expandable intervertebral implant and related methods
US10940016B2 (en) 2017-07-05 2021-03-09 Medos International Sarl Expandable intervertebral fusion cage
US12207856B2 (en) 2018-01-29 2025-01-28 Spinal Elements, Inc. Minimally invasive interbody fusion
US11583327B2 (en) 2018-01-29 2023-02-21 Spinal Elements, Inc. Minimally invasive interbody fusion
US12357291B2 (en) 2018-03-16 2025-07-15 Spinal Elements, Inc. Articulated instrumentation and methods of using the same
US11471145B2 (en) 2018-03-16 2022-10-18 Spinal Elements, Inc. Articulated instrumentation and methods of using the same
US11446156B2 (en) 2018-10-25 2022-09-20 Medos International Sarl Expandable intervertebral implant, inserter instrument, and related methods
US11013530B2 (en) 2019-03-08 2021-05-25 Medos International Sarl Surface features for device retention
US11241252B2 (en) 2019-03-22 2022-02-08 Medos International Sarl Skin foundation access portal
US12089873B2 (en) 2019-03-22 2024-09-17 Medos International Sàrl Skin foundation access portal
US11129727B2 (en) 2019-03-29 2021-09-28 Medos International Sari Inflatable non-distracting intervertebral implants and related methods
US11813026B2 (en) 2019-04-05 2023-11-14 Medos International Sarl Systems, devices, and methods for providing surgical trajectory guidance
US11806245B2 (en) 2020-03-06 2023-11-07 Eit Emerging Implant Technologies Gmbh Expandable intervertebral implant
US11426286B2 (en) 2020-03-06 2022-08-30 Eit Emerging Implant Technologies Gmbh Expandable intervertebral implant
US12426868B2 (en) 2020-09-23 2025-09-30 DePuy Synthes Products, Inc. Balloon with shape control for spinal procedures
US12303341B2 (en) 2021-03-12 2025-05-20 Medos International Srl Camera position indication systems and methods
US11771517B2 (en) 2021-03-12 2023-10-03 Medos International Sarl Camera position indication systems and methods
US11850160B2 (en) 2021-03-26 2023-12-26 Medos International Sarl Expandable lordotic intervertebral fusion cage
US12023258B2 (en) 2021-04-06 2024-07-02 Medos International Sarl Expandable intervertebral fusion cage
US11752009B2 (en) 2021-04-06 2023-09-12 Medos International Sarl Expandable intervertebral fusion cage
US12090064B2 (en) 2022-03-01 2024-09-17 Medos International Sarl Stabilization members for expandable intervertebral implants, and related systems and methods
US12427031B2 (en) 2022-08-08 2025-09-30 Medos International Sarl Expandable cage

Also Published As

Publication number Publication date
US20090082556A1 (en) 2009-03-26
US7595389B2 (en) 2009-09-29
US20080300395A1 (en) 2008-12-04
US7807819B2 (en) 2010-10-05
AU2003295600A8 (en) 2004-06-15
US8008474B2 (en) 2011-08-30
US20090298176A1 (en) 2009-12-03
WO2004045543A3 (en) 2005-04-21
US20090203895A1 (en) 2009-08-13
US8090542B2 (en) 2012-01-03
US7803933B2 (en) 2010-09-28
US20120052487A9 (en) 2012-03-01
EP2213738A2 (en) 2010-08-04
WO2004045543A2 (en) 2004-06-03
US20070088155A1 (en) 2007-04-19
EP2284266A3 (en) 2012-01-25
US20100267586A1 (en) 2010-10-21
US20090163702A1 (en) 2009-06-25
US20070141611A1 (en) 2007-06-21
EP1560931B1 (en) 2011-07-27
DK2284266T3 (en) 2014-01-13
US20100291681A1 (en) 2010-11-18
US20080108802A1 (en) 2008-05-08
US20080139798A1 (en) 2008-06-12
US20110111983A1 (en) 2011-05-12
US20080091001A1 (en) 2008-04-17
US20080293595A1 (en) 2008-11-27
US20070099862A1 (en) 2007-05-03
US7579457B2 (en) 2009-08-25
US7576197B2 (en) 2009-08-18
US8000902B2 (en) 2011-08-16
EP2278005A3 (en) 2012-05-23
US20090149644A1 (en) 2009-06-11
EP2305813A3 (en) 2012-03-28
US8030474B2 (en) 2011-10-04
PT2284266E (en) 2013-12-17
US20120135892A1 (en) 2012-05-31
EP2213738B1 (en) 2012-10-10
US7592444B2 (en) 2009-09-22
US20100152064A1 (en) 2010-06-17
US7655788B2 (en) 2010-02-02
US20080188647A1 (en) 2008-08-07
US7691997B2 (en) 2010-04-06
US20050255487A1 (en) 2005-11-17
US20070093653A1 (en) 2007-04-26
US20090163701A1 (en) 2009-06-25
US20080188648A1 (en) 2008-08-07
US20190345573A1 (en) 2019-11-14
ES2440284T3 (en) 2014-01-28
US20080293593A1 (en) 2008-11-27
US20080306015A1 (en) 2008-12-11
EP2305812A3 (en) 2012-06-06
EP2284266A2 (en) 2011-02-16
US7745611B2 (en) 2010-06-29
US7834170B2 (en) 2010-11-16
US7893247B2 (en) 2011-02-22
US20070088154A1 (en) 2007-04-19
EP2314691A2 (en) 2011-04-27
EP1560931A4 (en) 2006-08-02
US20110319474A1 (en) 2011-12-29
US7985854B2 (en) 2011-07-26
US7674896B2 (en) 2010-03-09
US20070088153A1 (en) 2007-04-19
EP2278005A2 (en) 2011-01-26
US20090088563A1 (en) 2009-04-02
US20100331214A1 (en) 2010-12-30
EP2213738A3 (en) 2010-11-17
US7576196B2 (en) 2009-08-18
ATE517992T1 (en) 2011-08-15
US20070088152A1 (en) 2007-04-19
US20070207974A1 (en) 2007-09-06
US20070072823A1 (en) 2007-03-29
US20100004142A1 (en) 2010-01-07
US20050245475A1 (en) 2005-11-03
EP1560931A2 (en) 2005-08-10
AU2003295600A1 (en) 2004-06-15
JP2006507841A (en) 2006-03-09
US20080091003A1 (en) 2008-04-17
US20050246794A1 (en) 2005-11-03
US20100029510A1 (en) 2010-02-04
US7642349B2 (en) 2010-01-05
US20080114162A1 (en) 2008-05-15
US20100075869A1 (en) 2010-03-25
JP2010187668A (en) 2010-09-02
US7507811B2 (en) 2009-03-24
US20090291497A1 (en) 2009-11-26
US7514550B2 (en) 2009-04-07
US8093370B2 (en) 2012-01-10
US20080091004A1 (en) 2008-04-17
US20080097090A1 (en) 2008-04-24
US20080108803A1 (en) 2008-05-08
US7645869B2 (en) 2010-01-12
EP2305812A2 (en) 2011-04-06
US7696344B2 (en) 2010-04-13
US20070031844A1 (en) 2007-02-08
US20080221317A1 (en) 2008-09-11
US20070039072A1 (en) 2007-02-15
EP2284266B1 (en) 2013-11-06
EP2305813A2 (en) 2011-04-06
US7795420B2 (en) 2010-09-14
US7608707B2 (en) 2009-10-27
US20100087335A1 (en) 2010-04-08
US7820809B2 (en) 2010-10-26
EP2314691A3 (en) 2012-01-18
US20100323922A1 (en) 2010-12-23
US7511132B2 (en) 2009-03-31
US20080091002A1 (en) 2008-04-17

Similar Documents

Publication Publication Date Title
US20050256525A1 (en) Dilation introducer for orthopedic surgery
US10293147B2 (en) Telescopic percutaneous tissue dilation systems and related methods
EP3205371B1 (en) Telescopic percutaneous tissue dilation systems and related methods of producing
US20080287981A1 (en) Dilation introducer and methods for orthopedic surgery
US12268423B2 (en) Stabilization system, implant, and methods for preventing relative motion between sections of tissue
US7087058B2 (en) Method and apparatus for providing posterior or anterior trans-sacral access to spinal vertebrae
US9168033B2 (en) Interspinous implants and methods for implanting same
US8075593B2 (en) Interspinous implants and methods for implanting same
US7641657B2 (en) Method and apparatus for providing posterior or anterior trans-sacral access to spinal vertebrae
JP3573461B2 (en) Modular intramedullary nail inserted into cannula
US11191575B2 (en) Systems and methods for off-axis augmentation of a vertebral body
US20040133201A1 (en) Methods and apparatuses for treating the spine through an access device
KR101469567B1 (en) Interspinous implants and methods for implanting same
US20130012955A1 (en) System and Method for Pedicle Screw Placement in Vertebral Alignment
JP6983204B2 (en) Systems and methods for intramedullary nail implantation
JP2021000440A (en) Systems and methods for intramedullary nail implantation
EP4601558A1 (en) Lateral mass drill guide system
AU2023361396A1 (en) Spinal decortication and grafting

Legal Events

Date Code Title Description
AS Assignment

Owner name: TRIAGE MEDICAL INC., CALIFORNIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:CULBERT, BRAD;OLMOS, FAUSTO;WARREN, CHRISTOPHER;REEL/FRAME:015719/0982

Effective date: 20050210

AS Assignment

Owner name: INTERVENTIONAL SPINE, INC., CALIFORNIA

Free format text: CHANGE OF NAME;ASSIGNOR:TRIAGE MEDICAL, INC.;REEL/FRAME:020236/0722

Effective date: 20061128

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION