[go: up one dir, main page]

WO2000032218A1 - Formule a liberation prolongee comprenant la gonadoliberine-ii - Google Patents

Formule a liberation prolongee comprenant la gonadoliberine-ii Download PDF

Info

Publication number
WO2000032218A1
WO2000032218A1 PCT/GB1999/004045 GB9904045W WO0032218A1 WO 2000032218 A1 WO2000032218 A1 WO 2000032218A1 GB 9904045 W GB9904045 W GB 9904045W WO 0032218 A1 WO0032218 A1 WO 0032218A1
Authority
WO
WIPO (PCT)
Prior art keywords
xaa
peptide
polymer
gnrh
gly
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.)
Ceased
Application number
PCT/GB1999/004045
Other languages
English (en)
Inventor
Steve Qi
Karen Akinsanya
Amanda Hayward
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.)
Ferring BV
Original Assignee
Ferring BV
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
Priority to HR20010421A priority Critical patent/HRP20010421A2/hr
Priority to EEP200100293A priority patent/EE200100293A/xx
Priority to SK755-2001A priority patent/SK7552001A3/sk
Priority to IL14349699A priority patent/IL143496A0/xx
Priority to MXPA01005543A priority patent/MXPA01005543A/es
Priority to CA002353798A priority patent/CA2353798A1/fr
Priority to JP2000584909A priority patent/JP2002531411A/ja
Priority to BR9915943-0A priority patent/BR9915943A/pt
Priority to PL99348575A priority patent/PL348575A1/xx
Application filed by Ferring BV filed Critical Ferring BV
Priority to EP99958357A priority patent/EP1140133A1/fr
Priority to AU15732/00A priority patent/AU770676B2/en
Priority to KR1020017006883A priority patent/KR20010089538A/ko
Priority to NZ511984A priority patent/NZ511984A/xx
Publication of WO2000032218A1 publication Critical patent/WO2000032218A1/fr
Priority to NO20012636A priority patent/NO20012636L/no
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K7/04—Linear peptides containing only normal peptide links
    • C07K7/23—Luteinising hormone-releasing hormone [LHRH]; Related peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • A61K38/09—Luteinising hormone-releasing hormone [LHRH], i.e. Gonadotropin-releasing hormone [GnRH]; Related peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
    • 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
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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

Definitions

  • the present invention relates to a pharmaceutical preparatior that releases a therapeutic agent over an extended period
  • GnRH gonadotropin releasing hormone
  • LHRH gonadotropin releasing hormone
  • FSH follicle-stimulating hormone
  • GnRH pyroGlu-H ⁇ s-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH 2 (SEQ I D No 5)
  • GnRH-II pyroGlu-H ⁇ s-Trp-Ser-His-Gly-Trp-Tyr-Pro-Gly-NH 2 (SEQ I D No 6)
  • GnRH-II is, to some extent, misleading The new peptide is a separate gene product, and is clearly distinguishable from GnRH in its tissue distribution It seems unlikely that GnRH-II acts as an endogenous releaser of LH and FSH Since no clear evidence for a physiological role for GnRH-II has been presented, no attentio ⁇ has been paid to the practical aspects of using this peptide as a therapeutic agent
  • GnRH-II has an important role in the function of a number of organs For example, it influences osteogenesis and it modulates the proliferation of prostatic epithelial cells Accordingly, we have considered the means by which this agent and its analogues might usefully be delivered in a clinical situation and it is an object of the present invention to provide suitable formulations for acnieving this purpose
  • the formulations according to the present invention rely on the use of a biodegradable polymer to hold the peptide in a depot from which it is released into the systemic circulation at a controlled rate
  • These formulations comprise two key elements the biologically active peptide and the biodegradable polymer
  • the biologically active peptide is a decapeptide according to the sequence
  • Xaa 1 is His or Tyr
  • Xaa 3 is Tyr or Arg
  • the polymer is any pharmaceutically acceptable biodegradable polymer, and preferably a co- polymer of glycolic and lactic acids
  • the invention further comprises the use of the formulations for the treament of human pathologies
  • Figure 1 shows the effect of increasing doses of GnRH-II on serum calcium concentrations in ova ⁇ ectomised rats.
  • ammo acids have their conventional meanings and indicate the natural L-isomer (except for the achiral ammo acid glycine)
  • the invention as disclosed herein comprises a pharmaceutical formulation that releases a therapeutic peptide at a controlled rate and for an extended period of time (i e for a period of at least one day, preferably several days, and more preferably at least one week), particularly for the treatment of diseases of the bone and prostate
  • the therapeutic peptide is a decapeptide according to the sequence
  • Xaa 1 is either His or Tyr Xaa 2 is either Trp or Leu and Xaa 3 is either Tyr or Arg, provided that when Xaa 1 is Tyr and Xaa 2 is Leu then Xaa 3 is not Arg
  • Xaa 1 is His Xaa 2 is Trp and Xaa 3 is Tyr
  • acids for example, acetic acid t ⁇ fluoroacetic acid benzoic acid, hydrochloric acid, phosDho ⁇ c acid and the like
  • a second essential component of the formulation is a biodegradable, pharmaeutically acceptable polymer
  • polymers are known in the art They can either be homopolymers (i e polymers of a single monomer) or copolymers (i e formed from two or more different monomers) Suitable monomers include ammo and hydroxy dervatives of carboxylic acids
  • the polymer is composed of hydroxyacyl monome ⁇ c units, and more preferably of ⁇ - hydroxyacyl units
  • the polymer is a poly(glycol ⁇ c acid), a poly(lact ⁇ c acid) or a copolymer of glycolic and lactic acids
  • Such a polymer has the following chemical structure
  • R is hydrogen in poly(glycol ⁇ c acid), methyl in poly(lact ⁇ c acid), and randomly hydrogen or methyl in the copolymer
  • the peptide can either be incorporated into a matrix of the polymer, or, more preferably, it can be encapsulated by the polymer
  • the peptide that is encapsulated may be either a solid or in solution It is preferred for the peptide to be a solid
  • This formulation is useful in the treatment of human pathologies, including disorders of bone growth (including age-related osteoporosis and osteoporosis associated with post-menopausal hormone status primary and secondary hyperparathyroidism disuse osteoporosis diabetes-related osteoporosis, and glucocorticoid-related osteoporosis) and prostate growth (including benign prostatic hyperplasia and prostate cancer)
  • disorders of bone growth including age-related osteoporosis and osteoporosis associated with post-menopausal hormone status primary and secondary hyperparathyroidism disuse osteoporosis diabetes-related osteoporosis, and glucocorticoid-related osteoporosis
  • prostate growth including benign prostatic hyperplasia and prostate cancer
  • co er ses a method for the treatment of an individual suffering from a disorder of bone or prostate growth or considered to be at risk of so suffering
  • This method of t r eatment comprises the administration to said individual of a therapeutically effective amount of a formulation containing as an active principal, a peptide according to the sequence
  • the method of treatment may comprise a single administration of the formulation, but is more likely to comprise a course of repeated administrations
  • the frequency of the administrations may be from once per day to once per month
  • the amount of active peptide in each dose will depend on the dosing schedule and the route of administration Generally, it will be between one milligram (1mg) and one gram (1g)
  • the supervising physician will determine the precise dose depending on the parameters generally considered in the art to be relevant
  • the formulation is administered by intramuscular or subcutaneous injection
  • the peptides that comprise the active agents of the compositions of the present invention can be prepared by the methods generally known in the art
  • the peptides may be prepared by solid-phase synthesis This involves the sequential addition of ammo acid residues to a resin-bound intermediate according to the following strategy
  • a protected am o acid is reacted with a functionalised resin.
  • the protecting group (PG) is most commonly terf-butyloxycarbonyl (Boc) or 9- fluorenylmethyloxycarbonyl (Fmoc).
  • the functional group on the resin (FG) is commonly a chloroalkyl group, a hydroxyl group or an amine group.
  • the linker group (L) is an oxygen atom ( -O- ).
  • L is -NH-.
  • step two the protecting group (PG) is removed from the ⁇ -amino group.
  • PG is Boc
  • this can be accomplished by treating the resin with acids such as trifluoroacetic acid or hydrogen chloride in dichloromethane.
  • PG is Fmoc
  • the deprotection can be accomplished by treating the resin with bases such as piperidine.
  • step three the peptide chain is extended by one ammo acid residue.
  • a protected ammo acid is coupled to the amine group liberated in step two.
  • Many reagents are known in the art for achieving this conversion.
  • One combination is dicyclohexylcarbodiimide (DCC) and hydroxybenzotriazole (HOBt).
  • DCC dicyclohexylcarbodiimide
  • HOBt hydroxybenzotriazole
  • a base will also be necessary Suitable bases include t ⁇ ethylamine and N.N- diisopropylethylamine.
  • the solvent will generally be dichloromethane, dimethylformamide, or a mixture of these If the side chains of the ammo acids (Aaa - Nnn) contain reactive groups (for example ammo groups, carboxylic acid groups, hydroxyl groups) then these will need protecting
  • the protecting groups chosen for the side chains are generally those that are stable un ⁇ er the conditions required to remove the protecting group (PG) from the ⁇ -amino group If PG is Fmoc, then the side chain protecting groups can conveniently be based on tert-butyl chemistry. On the other hand, if PG is Boc, then the side chain protecting groups can be based on fluorenylmethyl chemistry Other protecting groups known in the art can also be used.
  • step four the deprotection/chain extension cycle is repeated until the desired peptide sequence has been constructed.
  • step five the completed peptide is liberated from the resin.
  • Protecting groups are removed from the side chains either before or after the cleavage.
  • L is -NH-
  • the peptide liberated is in the form of the C-terminal amide.
  • L is -0-
  • the peptide liberated is often the C-terminal free acid and a second step is required to form the C-terminal amide.
  • the peptides may also be prepared by solution-phase synthesis, and this may be more convenient when large quantities of material are needed.
  • the formulation may take the form of a simple dispersion of the peptide in a matrix of the polymer, or the peptide may be microencapsulated with the polymer.
  • Dispersions can be prepared by mixing the peptide (as a solid) and the polymer to homogeneity, then compressing the mixture to form a solid mass. It may be necessary to add a binding agent to the mixture in order to achieve a suitably cohesive composition. The mass can then be ground up to give particles suitable for suspension in a biologically compatible liquid (such as water or isotonic saline) and injection.
  • a biologically compatible liquid such as water or isotonic saline
  • Microencapsulated formulations can be prepared either from the solid peptide (as a powder) or from a solution and particularly an aqueous solution, of the peptide
  • the polymer is first dissolved in a suitable organic solvent
  • the peptide is then added to this solution and the mixture is vigorously stirred to disperse the peptide in the organic phase
  • a second organic solvent is then added This second solvent is chosen to reduce the solubility of the polymer in the organic phase
  • the polymer comes out of solution to form a coating around the particles of solid peptide (or around the droplets of dispersed aqueous solution)
  • the resultant microcapsules are then hardened by washing to remove traces of the organic solvents They are then ready to be suspended in an appropriate liquid for a ⁇ ministration
  • This peptide was prepared using standard solid-phase methods starting from Boc-
  • Benzot ⁇ azolyl esters were used as the activated esters throughout the synthesis These were prepared from the corresponding protected ammo acids by reaction with 1 -hydroxy benzotriazole (1 eq ) and dicyclohexylcarbodiimide (1 eq ) The quantities used (in relation to the resin substitution capacity) are listed in Table 2
  • Example 1A The peptidoresm prepared in Example 1A was placed in a linen bag in a pressure vessel The vessel was then charged with gaseous ammonia to a final pressure of 4 atm After 72h the excess ammonia was vented and the resin was extracted with acetic acid (3* 10OmL) and ethanol (3 ⁇ 1 OOmL) The combined extracts were degassed with nitrogen, 10% palladium-on-carbon was added, and the mixture was stirred under an atmosphere of hydrogen When the reaction was complete (as judged by HPLC), the mixture was filtered and the filtrate was evaporated The residue was purified by reverse-phase HPLC to give the title compound
  • Copoly(D,L-lact ⁇ c acid, glycolic acid) with a lactic acid/glycolic acid ratio of 50/50 is used to a solution of this polymer (3 7g) in dichloromethane (100mL) in a reaction vessel equipped with a stirrer is added GnRH-II acetate (0 15g, prepared by dissolving the peptide of example 1 in acetic acid and lyophilismg the resultant solution) The mixture is stirred at 500revolut ⁇ ons/m ⁇ nute, then silico ⁇ e oil (Dow Corning 360 Medical Fluid®, 45g) is added over 0 minutes The mixture is then introduced as a thin jet into caprylic-cap ⁇ c acid-trigiyce ⁇ de (Miglyol® 812, 3 3L) with continuous stirring at lOOOrevolutions/minute When addition is complete, stirring is continued for 1 hour, then the microcapsules are collected by filtration, washed twice with isopropanol, and
  • the peptides of the invention caused significant effects at concentrations below 10O ⁇ M
  • Bone marrow cells removed from human bone fragments were cultured in the presence of 10nM 1 ,25-(OH) 2 vitamin D 3 for seven days to generate multinucleated osteoclasts using standard techniques known in the art (Takahashi et al , Endocnnol 122 1473-1482, 1988)
  • the culture medium ( ⁇ -MEM) was removed and replaced by a fresh phenol red free medium supplemented with antibiotics and 10% charcoal-stripped heat-inactivated FCS containing GnRH-l, GnRH-II or analogues and the cultures were maintained for a further 24 hours
  • Floating cells were harvested and osteoclasts stained for tartrate-resistant aci ⁇ phosphatase (TRAP) expression a marker of osteoclast differentiation ( Hughes et al Nat Med 2 1 132-1 1 35 1996)
  • the peptides of the invention caused significant effects at concentrations below 100 ⁇ M
  • Bone mineral density was assessed by dual energy x-ray absorptometry-DEXA) On day 28 serum calcium levels were determined by colo ⁇ met ⁇ c assay using a commercial kit
  • Example 1 demonstrates the preparation of the peptides of the invention, which can then be formulated as illustrated in Example 2
  • Examples 3 to 7 demonstrate the biological activity of the peptides of interest
  • the scope of the invention is not intended to be limited in any way by these Examples
  • variety of controlled release formulations of these peptides can be prepared by varying the polymer and/or the physical nature of the combination of the peptide and polymer
  • these variations give formulations with equivalent biological properties and are intended to be within the scope of the invention as defined in the following Claims
  • SEQ I D Nos 1 to 4 referred to in Example 5 are as follows

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Endocrinology (AREA)
  • Epidemiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Rheumatology (AREA)
  • Diabetes (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Reproductive Health (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Emergency Medicine (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Medicinal Preparation (AREA)

Abstract

Cette formule pharmaceutique est destinée à la libération prolongée d'un peptide thérapeutique, ou d'un sel de celui-ci, lequel peptide possède la séquence pyroGlu-His-Trp-Ser-Xaa?1Gly-Xaa2-Xaa3¿-Pro-Gly-NH¿2? Dans laquelle Xaa?1¿ représente His ou Tyr, Xaa2 représente Trp ou Leu, et Xaa3 représente Tyr ou Arg, à condition que lorsque Xaa1 représente Tyr et Xaa2 représente Leu, alors Xaa3 ne représente pas Arg, et elle comprend en outre un polymère biodégradable, acceptable sur le plan pharmacologique. On peut utiliser cette formule pour traiter des troubles des os et de la prostate.
PCT/GB1999/004045 1998-12-03 1999-12-02 Formule a liberation prolongee comprenant la gonadoliberine-ii Ceased WO2000032218A1 (fr)

Priority Applications (14)

Application Number Priority Date Filing Date Title
PL99348575A PL348575A1 (en) 1998-12-03 1999-12-02 Controlled release formulation comprising gnrh-ii
SK755-2001A SK7552001A3 (en) 1998-12-03 1999-12-02 Controlled release formulation comprising gnrh-ii
IL14349699A IL143496A0 (en) 1998-12-03 1999-12-02 Controlled release formulation comprising gnrh-ii
MXPA01005543A MXPA01005543A (es) 1998-12-03 1999-12-02 Formulacion de liberacion controlada que consta de gnrh-ii.
CA002353798A CA2353798A1 (fr) 1998-12-03 1999-12-02 Formule a liberation prolongee comprenant la gonadoliberine-ii
JP2000584909A JP2002531411A (ja) 1998-12-03 1999-12-02 Ｇｎｒｈ−ｉｉを含んで成る制御放出製剤
BR9915943-0A BR9915943A (pt) 1998-12-03 1999-12-02 Formulação de liberação controlada compreendendo gnrh-ii
HR20010421A HRP20010421A2 (en) 1998-12-03 1999-12-02 Controlled release formulation comprising gnrh-ii
EP99958357A EP1140133A1 (fr) 1998-12-03 1999-12-02 Formule a liberation prolongee comprenant la gonadoliberine-ii
EEP200100293A EE200100293A (et) 1998-12-03 1999-12-02 Kontrollitud vabanemisega ravivorm, mis sisaldab GnRH-II
AU15732/00A AU770676B2 (en) 1998-12-03 1999-12-02 Controlled release formulation comprising GnRH-II
KR1020017006883A KR20010089538A (ko) 1998-12-03 1999-12-02 Ｇｎｒｈ-ｉｉ를 포함하는 조절 방출형 제형
NZ511984A NZ511984A (en) 1998-12-03 1999-12-02 Controlled release formulation comprising GnRH-II
NO20012636A NO20012636L (no) 1998-12-03 2001-05-29 Kontrollert frigivelsesformulering som omfatter GNRH-II

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9826662.0 1998-12-03
GB9826662A GB2344287A (en) 1998-12-03 1998-12-03 Controlled release pharmaceutical formulation

Publications (1)

Publication Number Publication Date
WO2000032218A1 true WO2000032218A1 (fr) 2000-06-08

Family

ID=10843631

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1999/004045 Ceased WO2000032218A1 (fr) 1998-12-03 1999-12-02 Formule a liberation prolongee comprenant la gonadoliberine-ii

Country Status (22)

Country Link
EP (1) EP1140133A1 (fr)
JP (1) JP2002531411A (fr)
KR (1) KR20010089538A (fr)
CN (1) CN1332635A (fr)
AU (1) AU770676B2 (fr)
BR (1) BR9915943A (fr)
CA (1) CA2353798A1 (fr)
CZ (1) CZ20011893A3 (fr)
EE (1) EE200100293A (fr)
GB (1) GB2344287A (fr)
HR (1) HRP20010421A2 (fr)
HU (1) HUP0104943A3 (fr)
IL (1) IL143496A0 (fr)
MX (1) MXPA01005543A (fr)
NO (1) NO20012636L (fr)
NZ (1) NZ511984A (fr)
PL (1) PL348575A1 (fr)
RU (1) RU2233170C2 (fr)
SK (1) SK7552001A3 (fr)
TR (1) TR200102273T2 (fr)
WO (1) WO2000032218A1 (fr)
ZA (1) ZA200104530B (fr)

Cited By (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007012430A1 (fr) * 2005-07-26 2007-02-01 Georg-August-Universität-Göttingen Methode pouvant induire et accelerer l'apoptose dans des cellules cancereuses
WO2010111617A2 (fr) 2009-03-27 2010-09-30 Van Andel Research Institute Peptides de l'hormone parathyroïdienne et peptides de la protéine apparentée à l'hormone parathyroïdienne ainsi que des procédés d'utilisation
WO2011032099A1 (fr) 2009-09-11 2011-03-17 The Board Of Trustees Of The University Of Illinois Méthodes pour traiter un disfonctionnement diastolique et états associés
WO2011056572A1 (fr) 2009-10-27 2011-05-12 The Board Of Trustees Of The University Of Illinois Procédés de diagnostic de dysfonctionnement diastolique
WO2011075393A2 (fr) 2009-12-18 2011-06-23 Indiana University Research And Technology Corporation Co-agonistes du récepteur du glucagon/glp-i
WO2011094337A1 (fr) 2010-01-27 2011-08-04 Indiana University Research And Technology Corporation Conjugués d'antagoniste du glucagon et d'agoniste du gip et compositions pour le traitement de troubles métaboliques et de l'obésité
WO2011116026A2 (fr) 2010-03-15 2011-09-22 The Board Of Trustees Of The University Of Illinois Inhibiteurs des interactions de liaison de sous unité alpha d'intégrine ƒà-de protéine g
WO2011159895A2 (fr) 2010-06-16 2011-12-22 Indiana University Research And Technology Corporation Agonistes de l'insuline à une seule chaîne très actifs au niveau du récepteur à l'insuline
WO2012001149A2 (fr) 2010-07-02 2012-01-05 Georg-August-Universität Göttingen Compositions pharmaceutiques et méthodes d'induction et d'augmentation de l'apoptose dans des cellules tumorales
WO2012088116A2 (fr) 2010-12-22 2012-06-28 Indiana University Research And Technology Corporation Analogues du glucagon présentant une activité de récepteur de gip
WO2012087943A2 (fr) 2010-12-20 2012-06-28 The Regents Of The University Of Michigan Inhibiteurs de l'interaction de liaison entre le récepteur du facteur de croissance épidermique et la protéine de choc thermique 90
WO2012177443A2 (fr) 2011-06-22 2012-12-27 Indiana University Research And Technology Corporation Co-agonistes du récepteur du glucagon et du récepteur du gpl-1
WO2013074910A1 (fr) 2011-11-17 2013-05-23 Indiana University Research And Technology Corporation Peptides de la superfamille du glucagon présentant une action sur les récepteurs aux glucocorticoïdes
WO2013096386A1 (fr) 2011-12-20 2013-06-27 Indiana University Research And Technology Corporation Analogues d'insuline à base de ctp pour le traitement du diabète
WO2013188740A1 (fr) 2012-06-14 2013-12-19 Ambrx, Inc. Anticorps anti-psma conjugués à des polypeptides de ligand de récepteur nucléaire
WO2013192130A1 (fr) 2012-06-21 2013-12-27 Indiana University Research And Technology Corporation Analogues du glucagon présentant une activité sur le récepteur du gip
WO2013192129A1 (fr) 2012-06-21 2013-12-27 Indiana University Research And Technology Corporation Analogues du glucagon présentant une activité sur le récepteur du gip
WO2014052451A2 (fr) 2012-09-26 2014-04-03 Indiana University Research And Technology Corporation Dimères analogues de l'insuline
WO2014158900A1 (fr) 2013-03-14 2014-10-02 Indiana University Research And Technology Corporation Conjugués d'insuline-incrétine
WO2016049190A1 (fr) 2014-09-24 2016-03-31 Indiana University Research And Technology Corporation Conjugués d'insuline-incrétines
WO2016123143A1 (fr) 2015-01-26 2016-08-04 The University Of Chicago Lymphocytes t à récepteur d'antigène chimérique (car) reconnaissant le récepteur il 13rα2 spécifique au cancer
US9415123B2 (en) 2011-10-10 2016-08-16 The Regents Of The University Of Michigan Polymeric nanoparticles for ultrasound imaging and therapy
WO2019006235A1 (fr) 2017-06-30 2019-01-03 Amgen Inc. Procédés de traitement d'une insuffisance cardiaque avec des activateurs de sarcomères cardiaques
US10189908B2 (en) 2014-02-05 2019-01-29 The University Of Chicago Chimeric antigen receptors recognizing cancer-specific TN glycopeptide variants
WO2019028316A1 (fr) 2017-08-03 2019-02-07 Amgen Inc. Mutéines d'interleukine-21 et méthodes de traitement
WO2019056023A2 (fr) 2017-09-18 2019-03-21 The Regents Of The University Of California Anticorps contre claudin 6 et procédés de traitement du cancer
US10308719B2 (en) 2015-01-26 2019-06-04 The University Of Chicago IL13Rα2 binding agents and use thereof in cancer treatment
WO2019140196A1 (fr) 2018-01-12 2019-07-18 Amgen Inc. Anticorps anti-pd1 et méthodes de traitement
WO2020055913A1 (fr) 2018-09-10 2020-03-19 Cardax, Inc. Procédés de réduction de la protéine c réactive et/ou de traitement d'une maladie cardiovasculaire
US10640504B2 (en) 2017-09-08 2020-05-05 Amgen Inc. Inhibitors of KRAS G12C and methods of using the same
WO2020191344A1 (fr) 2019-03-20 2020-09-24 The Regents Of The University Of California Anticorps de claudin-6 bispécifiques
WO2020191342A1 (fr) 2019-03-20 2020-09-24 The Regents Of The University Of California Anticorps anti-claudine-6 et conjugués de médicaments
WO2020210376A1 (fr) 2019-04-09 2020-10-15 The Board Of Trustees Of The University Of Illinois Charbon actif hautement poreux à adsorption de médicament pour une administration de médicament améliorée
WO2020222668A1 (fr) 2019-04-30 2020-11-05 Instituto de Medicina Molecular João Lobo Antunes Inhibiteurs de la voie rank en combinaison avec des inhibiteurs de cdk
WO2020223177A1 (fr) 2019-04-29 2020-11-05 The Board Of Trustees Of The University Of Illinois Inhibiteurs de mek pour la cicatrisation de la cornée et la néovascularisation
WO2020263793A1 (fr) 2019-06-24 2020-12-30 Amgen Inc. Inhibition de la sirp-gamma pour le traitement du cancer
WO2021042048A1 (fr) 2019-08-30 2021-03-04 Research Institute At Nationwide Children's Hospital Cuivre-atsm pour le traitement de troubles neurodégénératifs associés à un dysfonctionnement mitochondrial
US11034962B2 (en) 2015-08-04 2021-06-15 The University Of Chicago Inhibitors of CACNA1A/ALPHA1A subunit internal ribosomal entry site (IRES) and methods of treating spinocerebellar ataxia type 6
WO2022015853A2 (fr) 2020-07-15 2022-01-20 Amgen Inc. Blocage de tigit et de cd112r
WO2022159575A1 (fr) 2021-01-20 2022-07-28 Bioentre Llc Protéines de liaison à ctla4 et méthodes de traitement du cancer
WO2023137161A1 (fr) 2022-01-14 2023-07-20 Amgen Inc. Triple blocage de tigit, cd112r et pd-l1
US11975048B2 (en) 2019-03-26 2024-05-07 Novel Pharma Inc. Long-acting fatty acid-conjugated GnRH derivatives and pharmaceutical compositions containing same
US11986474B1 (en) 2023-06-27 2024-05-21 Cytokinetics, Incorporated Methods for treating heart failure by administering cardiac sarcomere activators
US12194039B2 (en) 2020-11-12 2025-01-14 Amgen Inc Methods of treating heart failure by administering omecamtiv mecarbil

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0616111D0 (en) 2006-06-16 2006-09-20 Ardana Bioscience Ltd Agents, methods and uses
CN104789524A (zh) * 2015-04-30 2015-07-22 四川大学 骨质疏松大鼠原代成骨细胞分离培养方法及应用
CA3050811A1 (fr) * 2017-01-20 2018-07-26 Immune System Regulation Holding Ab Nouveaux composes (immunorhelines)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0158987A2 (fr) * 1984-04-18 1985-10-23 Hoechst Aktiengesellschaft Emploi de la gonadolibérine et de ses antagonistes pour préparer un médicament pour traiter les troubles liés à la ménopause
US4835139A (en) * 1983-09-23 1989-05-30 Debiopharm S.A. Process for increasing the antagonistic effect of peptidic compounds on hormone-dependent diseases
WO1997047743A1 (fr) * 1996-06-13 1997-12-18 Zymogenetics, Inc. Recepteur humain de l'hormone de liberation de la gonadotrophine de type ii

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4540513A (en) * 1984-09-25 1985-09-10 Kanegafuchi Kagaku Kogyo Kabushiki Kaisha Decapeptide having gonadotropin releasing activity
US4721775A (en) * 1985-08-26 1988-01-26 Board Of Regents, The University Of Texas System Effective peptides related to the luteinizing hormone releasing hormone from L-amino acids
DE3634435A1 (de) * 1986-10-09 1988-04-14 Hoechst Ag Analoga von gonadoliberin mit verbesserter loeslichkeit, verfahren zu deren herstellung, diese enthaltende mittel und ihre verwendung
ZA918168B (en) * 1990-10-16 1993-04-14 Takeda Chemical Industries Ltd Prolonged release preparation and polymers thereof.
IT1243390B (it) * 1990-11-22 1994-06-10 Vectorpharma Int Composizioni farmaceutiche in forma di particelle atte al rilascio controllato di sostanze farmacologicamente attive e procedimento per la loro preparazione.
CA2192773C (fr) * 1995-12-15 2008-09-23 Hiroaki Okada Obtention d'une preparation a liberation prolongee pour injection
US5932547A (en) * 1996-07-03 1999-08-03 Alza Corporation Non-aqueous polar aprotic peptide formulations
GB2343182A (en) * 1998-10-27 2000-05-03 Ferring Bv Use of GnRH-II and analogues thereof for the treatment of osteoporosis

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4835139A (en) * 1983-09-23 1989-05-30 Debiopharm S.A. Process for increasing the antagonistic effect of peptidic compounds on hormone-dependent diseases
EP0158987A2 (fr) * 1984-04-18 1985-10-23 Hoechst Aktiengesellschaft Emploi de la gonadolibérine et de ses antagonistes pour préparer un médicament pour traiter les troubles liés à la ménopause
WO1997047743A1 (fr) * 1996-06-13 1997-12-18 Zymogenetics, Inc. Recepteur humain de l'hormone de liberation de la gonadotrophine de type ii

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ASANO M ET AL: "IN VIVO CHARACTERISTICS OF LOW MOLECULAR WEIGHT COPOLY(L-LACTIC ACID/GLYCOLIC ACID) FORMULATIONS WITH CONTROLLED RELEASE OF LUTEINIZING HORMONE-RELEASING HORMONE AGONIST", JOURNAL OF CONTROLLED RELEASE,NL,ELSEVIER SCIENCE PUBLISHERS B.V. AMSTERDAM, vol. 9, no. 2, 1 July 1989 (1989-07-01), pages 111 - 122, XP000611562, ISSN: 0168-3659 *
SHARP P.J. ET AL: "Effect of luteinising hormone releasing hormone and its analogues on plasma luteinising hormone concentrations in incubating bantam hens", BRITISH POULTRY SCIENCE, vol. 27, no. 1, 1986, pages 129 - 136, XP000885654 *
WHITE R B ET AL: "Second gene for gonadotropin-releasing hormone in humans.", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, (1998 JAN 6) 95 (1) 305-9., XP000882990 *

Cited By (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8334258B2 (en) 2005-07-26 2012-12-18 Georg-August-Universität Göttingen Stiftung Öffentlichen Rechts (Universitätsmedizin) Method for induction and enhancement of apoptosis in tumor cells
WO2007012430A1 (fr) * 2005-07-26 2007-02-01 Georg-August-Universität-Göttingen Methode pouvant induire et accelerer l'apoptose dans des cellules cancereuses
WO2010111617A2 (fr) 2009-03-27 2010-09-30 Van Andel Research Institute Peptides de l'hormone parathyroïdienne et peptides de la protéine apparentée à l'hormone parathyroïdienne ainsi que des procédés d'utilisation
WO2011032099A1 (fr) 2009-09-11 2011-03-17 The Board Of Trustees Of The University Of Illinois Méthodes pour traiter un disfonctionnement diastolique et états associés
WO2011056572A1 (fr) 2009-10-27 2011-05-12 The Board Of Trustees Of The University Of Illinois Procédés de diagnostic de dysfonctionnement diastolique
WO2011075393A2 (fr) 2009-12-18 2011-06-23 Indiana University Research And Technology Corporation Co-agonistes du récepteur du glucagon/glp-i
WO2011094337A1 (fr) 2010-01-27 2011-08-04 Indiana University Research And Technology Corporation Conjugués d'antagoniste du glucagon et d'agoniste du gip et compositions pour le traitement de troubles métaboliques et de l'obésité
WO2011116026A2 (fr) 2010-03-15 2011-09-22 The Board Of Trustees Of The University Of Illinois Inhibiteurs des interactions de liaison de sous unité alpha d'intégrine ƒà-de protéine g
WO2014043594A1 (fr) 2010-03-15 2014-03-20 The Board Of Trustees Of The University Of Illinois Inhibiteurs des interactions de liaison de la sous-unité alpha de protéine g-intégrine bêta
WO2011159895A2 (fr) 2010-06-16 2011-12-22 Indiana University Research And Technology Corporation Agonistes de l'insuline à une seule chaîne très actifs au niveau du récepteur à l'insuline
WO2012001149A2 (fr) 2010-07-02 2012-01-05 Georg-August-Universität Göttingen Compositions pharmaceutiques et méthodes d'induction et d'augmentation de l'apoptose dans des cellules tumorales
WO2012087943A2 (fr) 2010-12-20 2012-06-28 The Regents Of The University Of Michigan Inhibiteurs de l'interaction de liaison entre le récepteur du facteur de croissance épidermique et la protéine de choc thermique 90
US9029502B2 (en) 2010-12-20 2015-05-12 The Regents Of The University Of Michigan Inhibitors of the epidermal growth factor receptor-heat shock protein 90 binding interaction
WO2012088116A2 (fr) 2010-12-22 2012-06-28 Indiana University Research And Technology Corporation Analogues du glucagon présentant une activité de récepteur de gip
WO2012177443A2 (fr) 2011-06-22 2012-12-27 Indiana University Research And Technology Corporation Co-agonistes du récepteur du glucagon et du récepteur du gpl-1
US9415123B2 (en) 2011-10-10 2016-08-16 The Regents Of The University Of Michigan Polymeric nanoparticles for ultrasound imaging and therapy
WO2013074910A1 (fr) 2011-11-17 2013-05-23 Indiana University Research And Technology Corporation Peptides de la superfamille du glucagon présentant une action sur les récepteurs aux glucocorticoïdes
WO2013096386A1 (fr) 2011-12-20 2013-06-27 Indiana University Research And Technology Corporation Analogues d'insuline à base de ctp pour le traitement du diabète
WO2013188740A1 (fr) 2012-06-14 2013-12-19 Ambrx, Inc. Anticorps anti-psma conjugués à des polypeptides de ligand de récepteur nucléaire
WO2013192130A1 (fr) 2012-06-21 2013-12-27 Indiana University Research And Technology Corporation Analogues du glucagon présentant une activité sur le récepteur du gip
WO2013192129A1 (fr) 2012-06-21 2013-12-27 Indiana University Research And Technology Corporation Analogues du glucagon présentant une activité sur le récepteur du gip
WO2014052451A2 (fr) 2012-09-26 2014-04-03 Indiana University Research And Technology Corporation Dimères analogues de l'insuline
EP3395358A1 (fr) 2012-09-26 2018-10-31 Indiana University Research and Technology Corporation Dimères d'un analogue d'insuline
WO2014158900A1 (fr) 2013-03-14 2014-10-02 Indiana University Research And Technology Corporation Conjugués d'insuline-incrétine
US10189908B2 (en) 2014-02-05 2019-01-29 The University Of Chicago Chimeric antigen receptors recognizing cancer-specific TN glycopeptide variants
WO2016049190A1 (fr) 2014-09-24 2016-03-31 Indiana University Research And Technology Corporation Conjugués d'insuline-incrétines
WO2016123143A1 (fr) 2015-01-26 2016-08-04 The University Of Chicago Lymphocytes t à récepteur d'antigène chimérique (car) reconnaissant le récepteur il 13rα2 spécifique au cancer
US10851169B2 (en) 2015-01-26 2020-12-01 The University Of Chicago Conjugates of IL13Rα2 binding agents and use thereof in cancer treatment
US11673935B2 (en) 2015-01-26 2023-06-13 The University Of Chicago Car T-cells recognizing cancer-specific IL 13Ra2
US10308719B2 (en) 2015-01-26 2019-06-04 The University Of Chicago IL13Rα2 binding agents and use thereof in cancer treatment
US11827712B2 (en) 2015-01-26 2023-11-28 The University Of Chicago IL13Rα2 binding agents and use thereof
US11034962B2 (en) 2015-08-04 2021-06-15 The University Of Chicago Inhibitors of CACNA1A/ALPHA1A subunit internal ribosomal entry site (IRES) and methods of treating spinocerebellar ataxia type 6
EP4512470A2 (fr) 2017-06-30 2025-02-26 Amgen Inc. Méthodes de traitement de l'insuffisance cardiaque avec des activateurs du sarcomères cardiaques
US11931358B2 (en) 2017-06-30 2024-03-19 Amgen Inc. Methods of treating heart failure with cardiac sarcomere activators
US12295952B2 (en) 2017-06-30 2025-05-13 Cytokinetics, Inc. Methods of treating heart failure with cardiac sarcomere activators
US11576910B2 (en) 2017-06-30 2023-02-14 Amgen Inc. Methods of treating heart failure with cardiac sarcomere activators
WO2019006235A1 (fr) 2017-06-30 2019-01-03 Amgen Inc. Procédés de traitement d'une insuffisance cardiaque avec des activateurs de sarcomères cardiaques
WO2019028316A1 (fr) 2017-08-03 2019-02-07 Amgen Inc. Mutéines d'interleukine-21 et méthodes de traitement
US11541103B2 (en) 2017-08-03 2023-01-03 Amgen Inc. Interleukin-21 mutein/ anti-PD-1 antibody conjugates
EP4029877A1 (fr) 2017-08-03 2022-07-20 Amgen, Inc Mutéines d'interleukine-21 et méthodes de traitement
US10640504B2 (en) 2017-09-08 2020-05-05 Amgen Inc. Inhibitors of KRAS G12C and methods of using the same
WO2019056023A2 (fr) 2017-09-18 2019-03-21 The Regents Of The University Of California Anticorps contre claudin 6 et procédés de traitement du cancer
EP4435009A2 (fr) 2017-09-18 2024-09-25 The Regents of the University of California Anticorps anti-claudine6 et méthodes de traitement du cancer
WO2019140196A1 (fr) 2018-01-12 2019-07-18 Amgen Inc. Anticorps anti-pd1 et méthodes de traitement
US11518808B2 (en) 2018-01-12 2022-12-06 Amgen Inc. Anti-PD-1 antibodies and methods of treatment
WO2020055913A1 (fr) 2018-09-10 2020-03-19 Cardax, Inc. Procédés de réduction de la protéine c réactive et/ou de traitement d'une maladie cardiovasculaire
WO2020191342A1 (fr) 2019-03-20 2020-09-24 The Regents Of The University Of California Anticorps anti-claudine-6 et conjugués de médicaments
EP4527408A2 (fr) 2019-03-20 2025-03-26 The Regents of the University of California Anticorps anti-claudine-6 et conjugués de médicaments
WO2020191344A1 (fr) 2019-03-20 2020-09-24 The Regents Of The University Of California Anticorps de claudin-6 bispécifiques
US11975048B2 (en) 2019-03-26 2024-05-07 Novel Pharma Inc. Long-acting fatty acid-conjugated GnRH derivatives and pharmaceutical compositions containing same
WO2020210376A1 (fr) 2019-04-09 2020-10-15 The Board Of Trustees Of The University Of Illinois Charbon actif hautement poreux à adsorption de médicament pour une administration de médicament améliorée
WO2020223177A1 (fr) 2019-04-29 2020-11-05 The Board Of Trustees Of The University Of Illinois Inhibiteurs de mek pour la cicatrisation de la cornée et la néovascularisation
WO2020222668A1 (fr) 2019-04-30 2020-11-05 Instituto de Medicina Molecular João Lobo Antunes Inhibiteurs de la voie rank en combinaison avec des inhibiteurs de cdk
WO2020263793A1 (fr) 2019-06-24 2020-12-30 Amgen Inc. Inhibition de la sirp-gamma pour le traitement du cancer
WO2021042048A1 (fr) 2019-08-30 2021-03-04 Research Institute At Nationwide Children's Hospital Cuivre-atsm pour le traitement de troubles neurodégénératifs associés à un dysfonctionnement mitochondrial
US11919953B2 (en) 2020-07-15 2024-03-05 Amgen Inc. TIGIT and CD112R blockade
WO2022015853A2 (fr) 2020-07-15 2022-01-20 Amgen Inc. Blocage de tigit et de cd112r
US12194039B2 (en) 2020-11-12 2025-01-14 Amgen Inc Methods of treating heart failure by administering omecamtiv mecarbil
WO2022159575A1 (fr) 2021-01-20 2022-07-28 Bioentre Llc Protéines de liaison à ctla4 et méthodes de traitement du cancer
WO2023137161A1 (fr) 2022-01-14 2023-07-20 Amgen Inc. Triple blocage de tigit, cd112r et pd-l1
US11986474B1 (en) 2023-06-27 2024-05-21 Cytokinetics, Incorporated Methods for treating heart failure by administering cardiac sarcomere activators

Also Published As

Publication number Publication date
EP1140133A1 (fr) 2001-10-10
BR9915943A (pt) 2001-08-21
GB2344287A (en) 2000-06-07
IL143496A0 (en) 2002-04-21
GB9826662D0 (en) 1999-01-27
RU2233170C2 (ru) 2004-07-27
TR200102273T2 (tr) 2001-12-21
CZ20011893A3 (cs) 2002-05-15
PL348575A1 (en) 2002-06-03
EE200100293A (et) 2002-08-15
JP2002531411A (ja) 2002-09-24
CN1332635A (zh) 2002-01-23
HRP20010421A2 (en) 2002-06-30
KR20010089538A (ko) 2001-10-06
MXPA01005543A (es) 2003-07-14
NO20012636D0 (no) 2001-05-29
AU1573200A (en) 2000-06-19
SK7552001A3 (en) 2002-02-05
AU770676B2 (en) 2004-02-26
HUP0104943A2 (en) 2002-06-29
NO20012636L (no) 2001-07-12
ZA200104530B (en) 2002-06-04
CA2353798A1 (fr) 2000-06-08
NZ511984A (en) 2002-11-26
HUP0104943A3 (en) 2002-08-28

Similar Documents

Publication Publication Date Title
AU770676B2 (en) Controlled release formulation comprising GnRH-II
KR930008095B1 (ko) Lhrh 길항제로서 유용한 lhrh의 노나펩타이드 및 데카펩타이드 동족체
US5470947A (en) CHRH antagonists with low histamine release
AU756785B2 (en) Methods for accelerating bone and cartilage growth and repair
EP0438519B1 (fr) Peptides therapeutiques
US5084555A (en) An octapeptide bombesin analog
KR100225679B1 (ko) 노나펩티드 봄베신 길항제
JPH07507330A (ja) ポリペプチドのボンベシン拮抗物質
CA2178218A1 (fr) Analogues de hgh-rh (1-29)nh2 possedant une activite antagoniste
UA68407C2 (en) Antagonistic analogues of growth hormone releasing hormone (gh-rh) inhibiting activity of endogenous insulin-like growth factors
EP1124847B1 (fr) Analogues de lh-rh pour le traitement de l'osteoporose
BG107121A (bg) Нови lhrh-антагонисти, тяхното получаване и използване като лекарственo средствo
CA2058020C (fr) Courts peptides avec activite insulinique

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 99815183.1

Country of ref document: CN

ENP Entry into the national phase

Ref document number: 2000 15732

Country of ref document: AU

Kind code of ref document: A

AK Designated states

Kind code of ref document: A1

Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 511984

Country of ref document: NZ

WWE Wipo information: entry into national phase

Ref document number: 15732/00

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: PV2001-1893

Country of ref document: CZ

WWE Wipo information: entry into national phase

Ref document number: 143496

Country of ref document: IL

ENP Entry into the national phase

Ref document number: 2353798

Country of ref document: CA

Ref document number: 2353798

Country of ref document: CA

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: 2001/04530

Country of ref document: ZA

Ref document number: P20010421A

Country of ref document: HR

Ref document number: PA/a/2001/005543

Country of ref document: MX

Ref document number: 7552001

Country of ref document: SK

Ref document number: 1020017006883

Country of ref document: KR

Ref document number: 200104530

Country of ref document: ZA

ENP Entry into the national phase

Ref document number: 2000 584909

Country of ref document: JP

Kind code of ref document: A

WWE Wipo information: entry into national phase

Ref document number: IN/PCT/2001/00475/DE

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 1999958357

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 2001/02273

Country of ref document: TR

WWP Wipo information: published in national office

Ref document number: 1020017006883

Country of ref document: KR

WWP Wipo information: published in national office

Ref document number: 1999958357

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWE Wipo information: entry into national phase

Ref document number: 09857115

Country of ref document: US

WWP Wipo information: published in national office

Ref document number: PV2001-1893

Country of ref document: CZ

WWG Wipo information: grant in national office

Ref document number: 15732/00

Country of ref document: AU

WWW Wipo information: withdrawn in national office

Ref document number: 1020017006883

Country of ref document: KR

WWW Wipo information: withdrawn in national office

Ref document number: 1999958357

Country of ref document: EP