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WO2014081300A1 - Liposomes activables par des protéines de canal - Google Patents

Liposomes activables par des protéines de canal Download PDF

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Publication number
WO2014081300A1
WO2014081300A1 PCT/NL2013/050847 NL2013050847W WO2014081300A1 WO 2014081300 A1 WO2014081300 A1 WO 2014081300A1 NL 2013050847 W NL2013050847 W NL 2013050847W WO 2014081300 A1 WO2014081300 A1 WO 2014081300A1
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WO
WIPO (PCT)
Prior art keywords
alkyl
group
aryl
independently
liposome
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/NL2013/050847
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English (en)
Inventor
Marc Stefan Robillard
Wolter Ten Hoeve
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Tagworks Pharmaceuticals BV
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Tagworks Pharmaceuticals BV
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Publication date
Application filed by Tagworks Pharmaceuticals BV filed Critical Tagworks Pharmaceuticals BV
Publication of WO2014081300A1 publication Critical patent/WO2014081300A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
    • A61K47/6911—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome
    • 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 mechanism of liposome accumulation may be a combination of the leakiness of the newly forming or damaged capillaries and enhanced vascular permeation by the coated liposomal particles themselves.
  • Specific targeting involves the use of antibodies or ligands to tag liposomes so that they bind specifically to cells that express the appropriate cell-surface antigens or ligand receptors, respectively.
  • liposomes can be targeted to any cell surface structure that can be recognized by a fragment of a specific antibody, or to any receptor for which a small and specific ligand can be produced.
  • liposomes can be directed to specific classes of T and B lymphocytes or to tumor cells, preferentially expressing high levels of specific cell surface proteins.
  • the goals of ligand targeting of liposomes are to concentrate them selectively at the therapeutic site, decrease the required dose by reducing non-specific losses, and reduce systemic exposure to drugs with toxic side effects.
  • the TCO satisfies the following formula
  • E, G are part of the above mentioned 8-membered ring and can be fused to PQ, QP, QX, XQ, XZ, ZX, ZY, YZ, YA, AY, such that P, A are CR a or CX D , and such that CX D can only be present in A and P.
  • E, G are part of the above mentioned 8-membered ring and can be fused to QX, XQ, XZ, ZX, ZY, YZ.
  • XD is 0-C(0)-(LD) n -(DD), S-C(0)-(LD) n -(E ), 0-C(S)-(LD) n -(DD), S-C(S)-(L D ) n -(D D ), NRd-C(0)-(L D ) n -(D D ), NRd-C(S)-(L D ) complicat-(D D ), and then Y° is NHR d , OH, SH; or X is C(0)-(LD) n- (DD), C(S)-(LD) n -(DD); and then YD is CR3 ⁇ 4NHR d , CR3 ⁇ 4OH, CR3 ⁇ 4SH, NH-NH 2 , 0-NH 2 , NH-OH.
  • A is CR a Y° and one of P, Q, X, Z is CR a X D , or P is CR a Y° and one of A, Y, Z, X is CR a X D , or Y is CR a Y° and X or P is CR a X D , or Q is CR a Y° and Z or A is CR a X D , or either Z or X is CR a Y D and A or P is CR a X D , such that X D and Y° are positioned in a trans conformation with respect to one another; the remaining groups (from A,Y,Z,X,Q,P) being independently from each other CR a 2 , S, O, SiR3 ⁇ 4 such that P and A are CR3 ⁇ 4, and no adjacent pairs of atoms are present selected from the group consisting of O-O, O-S, and S-S, and such that Si,
  • X D is N-C(0)-(L D )n-(D D ), N-C(S)-(L D ) n -(D D ); Y° is NH;
  • Each R c as above indicated is independently selected from the group consisting of H, alkyl, aryl, O-alkyl, O-aryl, OH;
  • Each R d as above indicated is independently selected from H, Ci-6 alkyl and Ci-6 aryl;
  • TCO's as described above is well available to the skilled person. This expressly also holds for TCO's having one or more heteroatoms in the strained cycloalkene rings. References in this regard include Cere et al. Journal of Organic Chemistry 1980, 45, 261 and Prevost et al. Journal of the American Chemical Society 2009, 131, 14182.
  • TCO stands for irans-cyclooctene.
  • ircwis-cyclooctene is used here as possibly including one or more hetero- atoms, and particularly refers to a structure satisfying formula (la).
  • Preferred nucleophiles are amine, thiol or alcohol groups, as these are generally most nucleophilic in nature and therefore most effective.
  • R' and R" each independently being H, aryl or alkyl and R'" independently being aryl or alkyl
  • X-Y may be a single or a double bond
  • X and Y may be connected in a second ring structure apart from the 6-membered diazine.
  • the Activator e.g. a 1,2,4,5- tetrazine
  • the Activator has useful and beneficial pharmacological and ph arm aco -kinetic properties, implying that the Activator is non-toxic or at least sufficiently low in toxicity, produces metabolites that are also sufficiently low in toxicity, is sufficiently soluble in physiological solutions, can be applied in aqueous or other formulations that are routinely used in pharmaceutics, and has the right log D value where this value reflects the
  • the Activator according to the invention has an appropriate reactivity towards the Trigger-Construct, and this can be regulated by making the diene, particularly the 1,2,4,5-tetrazines, sufficiently electron deficient. Sufficient reactivity will ensure a fast retro Diels-Alder reaction with the Trigger-Construct as soon as it has been reached by the Activator.
  • Synthesis routes to the above activators are readily available to the skilled person, based on standard knowledge in the art. References to tetrazine synthesis routes include Lions et al, J. Org. Chem., 1965, 30, 318-319; Horwitz et al, J. Am. Chem. Soc, 1958, 80, 3155-3159; Hapiot et al, New. J. Chem., 2004, 28, 387-392, Kaim et al, Z. Naturforsch., 1995, 50b, 123-127.
  • amine functional Constructs these can be e.g. primary or secondary amine, aniline, imidazole or pyrrole type of moieties, so that the Construct is varying in leaving group character.
  • the drawn fused ring products may or may not tautomerize to other more favorable tautomers.
  • urethane (or carbamate) substituted TCOs gives release of an amine functional Construct from the adduct.
  • the tetrazine Activator is asymmetric and electron deficient. Note that use of an asymmetric tetrazine leads to formation of retro Diels-Alder adduct regiomers, apart from the stereo-isomers that are already formed when symmetric tetrazine are employed.
  • urethane (or carbamate) TCOs gives release of an amine functional Construct from the adduct.
  • the tetrazine Activator is symmetric and electron sufficient.
  • Rl and R2 are H.
  • the Shaker protein is a protein comprising mutation Pro475Cys in Shaker H4 (Accession P08510) or equivalent positions in proteins of the Shaker family such as Pro406Cys in Kv2.1, Gly229Cys in KvAP, Alal08Cys in KcsA, Glu92Cys in MthK, and Glyl43Cys in KirBac.
  • the liposom es are prepared, with a relatively rigid lipid to impart rigidity to the lipid bilayer.
  • the lipids forming the liposomes have a phase transition temperature of between about 37-70 °C.
  • the vesicle forming lipid is distearyi phosphatidylcholine (DSPC), which has a phase transition temperature of 62 °C.
  • Suitable hydrophilic polymers for use in the conjugates, where the polymers are also intended to extend liposome-circulation time include polyvinylpyrrolidone, poly inylmeihylether, polymethyloxazoline, polyethyloxazoline, polyhydroxypropyloxazoline,
  • polyhydroxyethylaerylate hydroxymethylcellulose, liydroxyethylceilulose, polyethyleneglycol, and polyaspartamide.
  • the targeting agent T T can comprise compounds including but not limited to antibodies, antibody fragments, e.g. Fab2, Fab, scFV, diabodies, triabodies, VHH, antibody (fragment) fusions (eg bi-specific and trispecific mAb fragments), proteins, peptides, e.g. octreotide and derivatives, VIP, MSH, LHRH, chemotactic peptides, bombesin, elastin, peptide mimetics, carbohydrates, monosacharides, polysaccharides, viruses, whole cells, (e.g.
  • bone marrow stem cells drugs, polymers, chemotherapeutic agents, receptor agonists and antagonists, cytokines, hormones, steroids, vitamins.
  • organic compounds envisaged within the context of the present invention are, or are derived from, estrogens, e.g.
  • a variety of methods are available for preparing a conjugate composed of an T T arid a vesicle-forming lipid.
  • water-soluble, amine- containing T T can be covalently attached to lipids, such as
  • a second general coupling method is applicable to thiol-T T , and involves formation of a disulfide or thioether bond between a lipid and. the T T .
  • a lipid amine such as phosphatidyl-ethanolamine
  • a pyridyldithio derivative which can react wit an exposed thiol group in the T T . Reaction conditions for such a method can be found, in Martin (1981).
  • the liposomes of the invention are preferably prepared to have
  • the liposomes may contain genes encoding any of a variety of circulating proteins, such as ai-aniitrypsin, clotting factors (e.g.. Factor VIII, Factor IX) and globins (e.g., ⁇ -globrn,
  • oligonucleotide segment designed, for sequence-specific binding to cellular RNA or DNA.
  • cytotoxic agents include antimetabolites, natural products and their analogs, enzyme inhibitors such as dihydrofolate reductase inhibitors, and thymidylate synthase inhibitors, DNA alkylators, radiation sensitizers, DNA intercalators, DNA cleavers, anti-tubulin agents, topoisomerases inhibitors, platinum-based drugs, the anthracycline family of drugs, the vinca drugs, the mitomycins, the bleomycins, the cytotoxic nucleosides, taxanes, lexitropsins, the pteridine family of drugs, diynenes, the podophyllotoxins, dolastatins,
  • the compound is useful for treatment of a plasma cell disorder, such as multiple myeloma, which is characterized by neoplasms of B-lymphocyte lineage cells.
  • a plasma cell disorder such as multiple myeloma
  • Therapeutic agents preferred for treatment of multiple myeloma include melphalan, cyclophosphamide, prednisone, chlorambucil, carmustine, dexamethasone, doxorubicin, cisplatin, paclitaxel, vincristine, lomustine, and interferon.
  • irstracytoplasmic delivery of plasmids, antisense oligonucleotides, and ribozymes for the treatment of cancer and viral infections.
  • L D is hnked to T R via N or NH or an aliphatic or aromatic carbon, wherein these atoms are part of the linker. It is further preferred that said N and NH moieties comprised in L D are bound to an aliphatic or aromatic carbon.
  • Activators for use with Triggers based on the cascade mechanism satisfy one of the following formulae:
  • Equatorial-(£ ' )-cyclooct-2-en- l-ol 154 mg, 1.22 mmol was dissolved in 10 mL dichloromethane.
  • 4-(N,N-dimethylamino)pyridine 300 mg, 2.46 mmol was added and the solution was cooled in an ice-bath.
  • a solution of 4-nitrobenzoyl chloride (268 mg, 1.44 mmol) in 5 mL dichloromethane was added in portions over a 5 min period. The solution was stirred for 4 days.
  • the solvent was removed by rotary evaporation and the residue was chromatographed on 19 g silica, using dichloromethane as the eluent.
  • the product fractions were rotary evaporated yielding a colourless solid.
  • the iodolactone was dissolved in 250 mL toluene, and DBU (65.2 g, 0.428 mol) was added. The mixture was allowed to stand overnight, after which it was heated under reflux for 75 min (NMR indicated full conversion). After cooling the reaction mixture, it was washed with 150 and 100 mL water. The successive aqueous layers were extracted with 250 mL toluene. The organic layers were dried and rotary evaporated and the residue was purified by Kugelrohr distillation to yield 38.86 g of the bicyclic olefin (0.234 mol, 94%, containing a trace of toluene).
  • TCO-l-doxorubucin (6.25 xlO "8 mol) was dissolved in DMSO (0.050 mL), and PBS (0.475 mL) was added slowly in aliquots of 0.010 mL, followed by mouse serum (0.475 mL). A portion of this mixture (0.200 mL) was equilibrated at 37 °C, and a solution of tetrazine (1.25 xlO "7 mol) in DMSO (0.005 mL) was added, and the solution was thoroughly mixed and incubated at 37 °C in the dark for 4 h.
  • the TCO stock solution (10 iL 25 mM; 2.5* 10 "7 mol) was added to a solution of the specific condition (100 iL). The mixture was stirred at the specific condition for a certain amount of time, and then the fate of the TCO compound was monitored by HPLC-MS/PDA analysis and/or GC-MS analysis, and an estimation of its stability was made.
  • Protein was isolated as described by Kocer et. al. (Kocer et al, 2007, Nat Prot).

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Dispersion Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

La présente invention concerne un liposome, comprenant une bicouche lipidique entourant une cavité, la bicouche comprenant une protéine de canal liée de façon réversible à un groupe alcénylène cyclique non aromatique à huit chaînons, de préférence un groupe cyclo-octène, et plus préférablement un groupe trans-cyclooctène. Les liposomes sont utilisés dans un kit comprenant le liposome, dont la membrane liposomale comprend une protéine de canal liée à un déclencheur, et un activateur pour le déclencheur, le déclencheur comprenant le groupe alcénylène cyclique non aromatique à huit chaînons, et l'activateur comprenant un diène.
PCT/NL2013/050847 2012-11-22 2013-11-22 Liposomes activables par des protéines de canal Ceased WO2014081300A1 (fr)

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Application Number Priority Date Filing Date Title
EP12193923.5 2012-11-22
EP12193923 2012-11-22

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WO2014081300A1 true WO2014081300A1 (fr) 2014-05-30

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Cited By (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8980864B2 (en) 2013-03-15 2015-03-17 Moderna Therapeutics, Inc. Compositions and methods of altering cholesterol levels
US8999380B2 (en) 2012-04-02 2015-04-07 Moderna Therapeutics, Inc. Modified polynucleotides for the production of biologics and proteins associated with human disease
US9107886B2 (en) 2012-04-02 2015-08-18 Moderna Therapeutics, Inc. Modified polynucleotides encoding basic helix-loop-helix family member E41
US9181319B2 (en) 2010-08-06 2015-11-10 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
US9186372B2 (en) 2011-12-16 2015-11-17 Moderna Therapeutics, Inc. Split dose administration
US9283287B2 (en) 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
US9334328B2 (en) 2010-10-01 2016-05-10 Moderna Therapeutics, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
US9428535B2 (en) 2011-10-03 2016-08-30 Moderna Therapeutics, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
US9464124B2 (en) 2011-09-12 2016-10-11 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
US9533047B2 (en) 2011-03-31 2017-01-03 Modernatx, Inc. Delivery and formulation of engineered nucleic acids
US9572897B2 (en) 2012-04-02 2017-02-21 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
US9597380B2 (en) 2012-11-26 2017-03-21 Modernatx, Inc. Terminally modified RNA
CN106749071A (zh) * 2017-01-10 2017-05-31 江西师范大学 一种芳香类1,2,4,5‑四嗪化合物的制备方法
WO2017175613A1 (fr) * 2016-04-06 2017-10-12 住友化学株式会社 Composé hétérocyclique
CN107281204A (zh) * 2017-05-04 2017-10-24 北京大学 一种非对称的1，2，4，5‑四嗪分子的应用
US9951069B1 (en) 2017-01-11 2018-04-24 Rodin Therapeutics, Inc. Bicyclic inhibitors of histone deacetylase
EP3268050A4 (fr) * 2015-03-09 2018-11-14 The Trustees of Columbia University in the City of New York Compositions de conjugués de protéines porogènes et procédés correspondants
US10130711B2 (en) 2013-06-19 2018-11-20 The Regents Of The University Of California Chemical structures for localized delivery of therapeutic agents
US10130723B2 (en) 2014-03-14 2018-11-20 The Regents Of The University Of California TCO conjugates and methods for delivery of therapeutic agents
US10323076B2 (en) 2013-10-03 2019-06-18 Modernatx, Inc. Polynucleotides encoding low density lipoprotein receptor
US10421756B2 (en) 2015-07-06 2019-09-24 Rodin Therapeutics, Inc. Heterobicyclic N-aminophenyl-amides as inhibitors of histone deacetylase
US10828373B2 (en) 2015-09-10 2020-11-10 Tambo, Inc. Bioorthogonal compositions
US10894797B2 (en) 2018-09-18 2021-01-19 Nikang Therapeutics, Inc. Fused tricyclic ring derivatives as SRC homology-2 phosphatase inhibitors
US10919902B2 (en) 2015-07-06 2021-02-16 Alkermes, Inc. Hetero-halo inhibitors of histone deacetylase
JP2022502463A (ja) * 2018-10-10 2022-01-11 タンボ・インコーポレイテッド 官能化シクロオクテンを調製するためのプロセス
US11225475B2 (en) 2017-08-07 2022-01-18 Alkermes, Inc. Substituted pyridines as inhibitors of histone deacetylase
US11253600B2 (en) 2017-04-07 2022-02-22 Tambo, Inc. Bioorthogonal compositions
US11560384B2 (en) 2017-05-04 2023-01-24 University Of Utah Research Foundation Benzonorbornadiene derivatives and reactions thereof
US11744801B2 (en) 2017-08-31 2023-09-05 Modernatx, Inc. Methods of making lipid nanoparticles
US11786607B2 (en) 2017-06-15 2023-10-17 Modernatx, Inc. RNA formulations
CN117700394A (zh) * 2024-02-06 2024-03-15 南京大学 一类可与非张力烯基硼酸快速环加成反应的四嗪类化合物及其生物医药应用
US12090235B2 (en) 2018-09-20 2024-09-17 Modernatx, Inc. Preparation of lipid nanoparticles and methods of administration thereof
US12522587B2 (en) 2018-05-04 2026-01-13 Remedy Plan, Inc. Cancer treatments targeting cancer stem cells

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003000233A2 (fr) * 2001-06-21 2003-01-03 Applied Nanosystems B.V. Liberation de petites molecules hydrophiles comprises dans des vesicules lipidiques
WO2003084508A1 (fr) * 2002-04-04 2003-10-16 Applied Nanosystems B.V. Administration d'une substance sur un site predetermine
WO2005051902A2 (fr) * 2003-11-25 2005-06-09 Applied Nanosystems B.V. Canal proteique mscl modifie
WO2009144659A1 (fr) * 2008-05-27 2009-12-03 Koninklijke Philips Electronics N.V. Protéines modifiées par un groupe azide
WO2010051530A2 (fr) * 2008-10-31 2010-05-06 The General Hospital Corporation Compositions et procédés d'administration d'une substance à une cible biologique
WO2012049624A1 (fr) * 2010-10-14 2012-04-19 Koninklijke Philips Electronics N.V. Kit et procédé de préciblage, et agents qu'ils utilisent
WO2012085789A1 (fr) * 2010-12-21 2012-06-28 Koninklijke Philips Electronics N.V. Agents pour l'élimination de biomolécules hors de la circulation
WO2012156919A1 (fr) * 2011-05-16 2012-11-22 Koninklijke Philips Electronics N.V. Activation d'un médicament bio-orthogonal

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003000233A2 (fr) * 2001-06-21 2003-01-03 Applied Nanosystems B.V. Liberation de petites molecules hydrophiles comprises dans des vesicules lipidiques
WO2003084508A1 (fr) * 2002-04-04 2003-10-16 Applied Nanosystems B.V. Administration d'une substance sur un site predetermine
WO2005051902A2 (fr) * 2003-11-25 2005-06-09 Applied Nanosystems B.V. Canal proteique mscl modifie
WO2009144659A1 (fr) * 2008-05-27 2009-12-03 Koninklijke Philips Electronics N.V. Protéines modifiées par un groupe azide
WO2010051530A2 (fr) * 2008-10-31 2010-05-06 The General Hospital Corporation Compositions et procédés d'administration d'une substance à une cible biologique
WO2012049624A1 (fr) * 2010-10-14 2012-04-19 Koninklijke Philips Electronics N.V. Kit et procédé de préciblage, et agents qu'ils utilisent
WO2012085789A1 (fr) * 2010-12-21 2012-06-28 Koninklijke Philips Electronics N.V. Agents pour l'élimination de biomolécules hors de la circulation
WO2012156919A1 (fr) * 2011-05-16 2012-11-22 Koninklijke Philips Electronics N.V. Activation d'un médicament bio-orthogonal

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BLACKMAN M L ET AL: "Tetrazine ligation: Fast bioconjugation based on inverse-electron-demand Diels-Alder reactivity", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, ACS PUBLICATIONS, US, vol. 130, no. 41, 15 October 2008 (2008-10-15), pages 13518 - 13519, XP002544618, ISSN: 0002-7863, DOI: 10.1021/JA8053805 *
FABIEN EMMETIERE ET AL: "18 F-Labeled-Bioorthogonal Liposomes for In Vivo Targeting", BIOCONJUGATE CHEMISTRY, vol. 24, no. 11, 4 November 2013 (2013-11-04), pages 1784 - 1789, XP055105344, ISSN: 1043-1802, DOI: 10.1021/bc400322h *
NEAL K. DEVARAJ ET AL: "Biomedical Applications of Tetrazine Cycloadditions", ACCOUNTS OF CHEMICAL RESEARCH, vol. 44, no. 9, 20 September 2011 (2011-09-20), pages 816 - 827, XP055040508, ISSN: 0001-4842, DOI: 10.1021/ar200037t *
RAFFAELLA ROSSIN ET AL: "In Vivo Chemistry for Pretargeted Tumor Imaging in Live Mice", ANGEWANDTE CHEMIE (INTERNATIONAL EDITION), WILEY - VCH VERLAG GMBH & CO, DE, vol. 49, no. 19, 26 April 2010 (2010-04-26), pages 3375 - 3378, XP002626136, ISSN: 1521-3773, [retrieved on 20100412], DOI: 10.1002/ANIE.200906294 *
ROSSELLA TARALLO ET AL: "Clickable Functionalization of Liposomes with the gH625 Peptide from Herpes simplex Virus Type I for Intracellular Drug Delivery", CHEMISTRY - A EUROPEAN JOURNAL, vol. 17, no. 45, 28 September 2011 (2011-09-28), pages 12659 - 12668, XP055105373, ISSN: 0947-6539, DOI: 10.1002/chem.201101425 *

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US9937233B2 (en) 2010-08-06 2018-04-10 Modernatx, Inc. Engineered nucleic acids and methods of use thereof
US9657295B2 (en) 2010-10-01 2017-05-23 Modernatx, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
US9334328B2 (en) 2010-10-01 2016-05-10 Moderna Therapeutics, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
US10064959B2 (en) 2010-10-01 2018-09-04 Modernatx, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
US9701965B2 (en) 2010-10-01 2017-07-11 Modernatx, Inc. Engineered nucleic acids and methods of use thereof
US9950068B2 (en) 2011-03-31 2018-04-24 Modernatx, Inc. Delivery and formulation of engineered nucleic acids
US9533047B2 (en) 2011-03-31 2017-01-03 Modernatx, Inc. Delivery and formulation of engineered nucleic acids
US9464124B2 (en) 2011-09-12 2016-10-11 Moderna Therapeutics, Inc. Engineered nucleic acids and methods of use thereof
US10022425B2 (en) 2011-09-12 2018-07-17 Modernatx, Inc. Engineered nucleic acids and methods of use thereof
US10751386B2 (en) 2011-09-12 2020-08-25 Modernatx, Inc. Engineered nucleic acids and methods of use thereof
US9428535B2 (en) 2011-10-03 2016-08-30 Moderna Therapeutics, Inc. Modified nucleosides, nucleotides, and nucleic acids, and uses thereof
US9271996B2 (en) 2011-12-16 2016-03-01 Moderna Therapeutics, Inc. Formulation and delivery of PLGA microspheres
US9186372B2 (en) 2011-12-16 2015-11-17 Moderna Therapeutics, Inc. Split dose administration
US9295689B2 (en) 2011-12-16 2016-03-29 Moderna Therapeutics, Inc. Formulation and delivery of PLGA microspheres
US9301993B2 (en) 2012-04-02 2016-04-05 Moderna Therapeutics, Inc. Modified polynucleotides encoding apoptosis inducing factor 1
US9827332B2 (en) 2012-04-02 2017-11-28 Modernatx, Inc. Modified polynucleotides for the production of proteins
US9255129B2 (en) 2012-04-02 2016-02-09 Moderna Therapeutics, Inc. Modified polynucleotides encoding SIAH E3 ubiquitin protein ligase 1
US9233141B2 (en) 2012-04-02 2016-01-12 Moderna Therapeutics, Inc. Modified polynucleotides for the production of proteins associated with blood and lymphatic disorders
US9283287B2 (en) 2012-04-02 2016-03-15 Moderna Therapeutics, Inc. Modified polynucleotides for the production of nuclear proteins
US9220755B2 (en) 2012-04-02 2015-12-29 Moderna Therapeutics, Inc. Modified polynucleotides for the production of proteins associated with blood and lymphatic disorders
US9050297B2 (en) 2012-04-02 2015-06-09 Moderna Therapeutics, Inc. Modified polynucleotides encoding aryl hydrocarbon receptor nuclear translocator
US9303079B2 (en) 2012-04-02 2016-04-05 Moderna Therapeutics, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
US9221891B2 (en) 2012-04-02 2015-12-29 Moderna Therapeutics, Inc. In vivo production of proteins
US9220792B2 (en) 2012-04-02 2015-12-29 Moderna Therapeutics, Inc. Modified polynucleotides encoding aquaporin-5
US9216205B2 (en) 2012-04-02 2015-12-22 Moderna Therapeutics, Inc. Modified polynucleotides encoding granulysin
US9192651B2 (en) 2012-04-02 2015-11-24 Moderna Therapeutics, Inc. Modified polynucleotides for the production of secreted proteins
US9149506B2 (en) 2012-04-02 2015-10-06 Moderna Therapeutics, Inc. Modified polynucleotides encoding septin-4
US9572897B2 (en) 2012-04-02 2017-02-21 Modernatx, Inc. Modified polynucleotides for the production of cytoplasmic and cytoskeletal proteins
US9587003B2 (en) 2012-04-02 2017-03-07 Modernatx, Inc. Modified polynucleotides for the production of oncology-related proteins and peptides
US9061059B2 (en) 2012-04-02 2015-06-23 Moderna Therapeutics, Inc. Modified polynucleotides for treating protein deficiency
US9114113B2 (en) 2012-04-02 2015-08-25 Moderna Therapeutics, Inc. Modified polynucleotides encoding citeD4
US9089604B2 (en) 2012-04-02 2015-07-28 Moderna Therapeutics, Inc. Modified polynucleotides for treating galactosylceramidase protein deficiency
US9675668B2 (en) 2012-04-02 2017-06-13 Moderna Therapeutics, Inc. Modified polynucleotides encoding hepatitis A virus cellular receptor 2
US9107886B2 (en) 2012-04-02 2015-08-18 Moderna Therapeutics, Inc. Modified polynucleotides encoding basic helix-loop-helix family member E41
US9782462B2 (en) 2012-04-02 2017-10-10 Modernatx, Inc. Modified polynucleotides for the production of proteins associated with human disease
US8999380B2 (en) 2012-04-02 2015-04-07 Moderna Therapeutics, Inc. Modified polynucleotides for the production of biologics and proteins associated with human disease
US10501512B2 (en) 2012-04-02 2019-12-10 Modernatx, Inc. Modified polynucleotides
US9814760B2 (en) 2012-04-02 2017-11-14 Modernatx, Inc. Modified polynucleotides for the production of biologics and proteins associated with human disease
US9828416B2 (en) 2012-04-02 2017-11-28 Modernatx, Inc. Modified polynucleotides for the production of secreted proteins
US9254311B2 (en) 2012-04-02 2016-02-09 Moderna Therapeutics, Inc. Modified polynucleotides for the production of proteins
US9878056B2 (en) 2012-04-02 2018-01-30 Modernatx, Inc. Modified polynucleotides for the production of cosmetic proteins and peptides
US9095552B2 (en) 2012-04-02 2015-08-04 Moderna Therapeutics, Inc. Modified polynucleotides encoding copper metabolism (MURR1) domain containing 1
US9597380B2 (en) 2012-11-26 2017-03-21 Modernatx, Inc. Terminally modified RNA
US8980864B2 (en) 2013-03-15 2015-03-17 Moderna Therapeutics, Inc. Compositions and methods of altering cholesterol levels
US10130711B2 (en) 2013-06-19 2018-11-20 The Regents Of The University Of California Chemical structures for localized delivery of therapeutic agents
US10953098B2 (en) 2013-06-19 2021-03-23 The Regents Of The University Of California Chemical structures for localized delivery of therapeutic agents
US10323076B2 (en) 2013-10-03 2019-06-18 Modernatx, Inc. Polynucleotides encoding low density lipoprotein receptor
US10342882B2 (en) 2014-03-14 2019-07-09 The Regents Of The University Of California TCO conjugates and methods for delivery of therapeutic agents
US10806807B2 (en) 2014-03-14 2020-10-20 The Regents Of The University Of California TCO conjugates and methods for delivery of therapeutic agents
US12257326B2 (en) 2014-03-14 2025-03-25 The Research Foundation For The State University Of New York TCO conjugates and methods for delivery of therapeutic agents
US10130723B2 (en) 2014-03-14 2018-11-20 The Regents Of The University Of California TCO conjugates and methods for delivery of therapeutic agents
EP3268050A4 (fr) * 2015-03-09 2018-11-14 The Trustees of Columbia University in the City of New York Compositions de conjugués de protéines porogènes et procédés correspondants
US10421756B2 (en) 2015-07-06 2019-09-24 Rodin Therapeutics, Inc. Heterobicyclic N-aminophenyl-amides as inhibitors of histone deacetylase
US10919902B2 (en) 2015-07-06 2021-02-16 Alkermes, Inc. Hetero-halo inhibitors of histone deacetylase
US11858939B2 (en) 2015-07-06 2024-01-02 Alkermes, Inc. Hetero-halo inhibitors of histone deacetylase
US12527874B2 (en) 2015-09-10 2026-01-20 Tambo, Inc. Bioorthogonal compositions
US10828373B2 (en) 2015-09-10 2020-11-10 Tambo, Inc. Bioorthogonal compositions
US10662157B2 (en) 2016-04-06 2020-05-26 Sumitomo Chemical Company, Limited Heterocyclic compound
US11124480B2 (en) 2016-04-06 2021-09-21 Sumitomo Chemical Company, Limited Heterocyclic compound
WO2017175613A1 (fr) * 2016-04-06 2017-10-12 住友化学株式会社 Composé hétérocyclique
CN106749071A (zh) * 2017-01-10 2017-05-31 江西师范大学 一种芳香类1,2,4,5‑四嗪化合物的制备方法
US11987580B2 (en) 2017-01-11 2024-05-21 Alkermes, Inc. Bicyclic inhibitors of histone deacetylase
US9951069B1 (en) 2017-01-11 2018-04-24 Rodin Therapeutics, Inc. Bicyclic inhibitors of histone deacetylase
US10793567B2 (en) 2017-01-11 2020-10-06 Rodin Therapeutics, Inc. Bicyclic inhibitors of histone deacetylase
US11225479B2 (en) 2017-01-11 2022-01-18 Alkermes, Inc. Bicyclic inhibitors of histone deacetylase
US11286256B2 (en) 2017-01-11 2022-03-29 Alkermes, Inc. Bicyclic inhibitors of histone deacetylase
US10519149B2 (en) 2017-01-11 2019-12-31 Rodin Therapeutics, Inc. Bicyclic inhibitors of histone deacetylase
US10696673B2 (en) 2017-01-11 2020-06-30 Rodin Therapeutics, Inc. Bicyclic inhibitors of histone deacetylase
US12296017B2 (en) 2017-04-07 2025-05-13 Tambo, Inc. Bioorthogonal compositions
US11253600B2 (en) 2017-04-07 2022-02-22 Tambo, Inc. Bioorthogonal compositions
US11560384B2 (en) 2017-05-04 2023-01-24 University Of Utah Research Foundation Benzonorbornadiene derivatives and reactions thereof
CN107281204A (zh) * 2017-05-04 2017-10-24 北京大学 一种非对称的1，2，4，5‑四嗪分子的应用
US11786607B2 (en) 2017-06-15 2023-10-17 Modernatx, Inc. RNA formulations
US11912702B2 (en) 2017-08-07 2024-02-27 Alkermes, Inc. Substituted pyridines as inhibitors of histone deacetylase
US11225475B2 (en) 2017-08-07 2022-01-18 Alkermes, Inc. Substituted pyridines as inhibitors of histone deacetylase
US12357575B2 (en) 2017-08-31 2025-07-15 Modernatx, Inc. Methods of making lipid nanoparticles
US11744801B2 (en) 2017-08-31 2023-09-05 Modernatx, Inc. Methods of making lipid nanoparticles
US12522587B2 (en) 2018-05-04 2026-01-13 Remedy Plan, Inc. Cancer treatments targeting cancer stem cells
US12264167B2 (en) 2018-09-18 2025-04-01 Nikang Therapeutics, Inc. Fused tricyclic ring derivatives as SRC homology-2 phosphate inhibitors
US10894797B2 (en) 2018-09-18 2021-01-19 Nikang Therapeutics, Inc. Fused tricyclic ring derivatives as SRC homology-2 phosphatase inhibitors
US11518772B2 (en) 2018-09-18 2022-12-06 Nikang Therapeutics, Inc. Fused tricyclic ring derivatives as Src homology-2 phosphate inhibitors
US11034705B2 (en) 2018-09-18 2021-06-15 Nikang Therapeutics, Inc. Fused tricyclic ring derivatives as Src homology-2 phosphate inhibitors
US11459340B2 (en) 2018-09-18 2022-10-04 Nikang Therapeutics, Inc. Tri-substituted heteroaryl derivatives as Src homology-2 phosphatase inhibitors
US12090235B2 (en) 2018-09-20 2024-09-17 Modernatx, Inc. Preparation of lipid nanoparticles and methods of administration thereof
JP2022502463A (ja) * 2018-10-10 2022-01-11 タンボ・インコーポレイテッド 官能化シクロオクテンを調製するためのプロセス
JP7650228B2 (ja) 2018-10-10 2025-03-24 タンボ・インコーポレイテッド 官能化シクロオクテンを調製するためのプロセス
US12194100B2 (en) 2018-10-10 2025-01-14 Tambo, Inc. Processes for preparing functionalized cyclooctenes
CN117700394B (zh) * 2024-02-06 2024-05-28 南京大学 一类可与非张力烯基硼酸快速环加成反应的四嗪类化合物及其生物医药应用
CN117700394A (zh) * 2024-02-06 2024-03-15 南京大学 一类可与非张力烯基硼酸快速环加成反应的四嗪类化合物及其生物医药应用

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