TW201300407A - Nav1.3及Nav1.7之強效及選擇性抑制劑 - Google Patents
Nav1.3及Nav1.7之強效及選擇性抑制劑 Download PDFInfo
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- TW201300407A TW201300407A TW101109226A TW101109226A TW201300407A TW 201300407 A TW201300407 A TW 201300407A TW 101109226 A TW101109226 A TW 101109226A TW 101109226 A TW101109226 A TW 101109226A TW 201300407 A TW201300407 A TW 201300407A
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- Prior art keywords
- methyl
- arginine
- residue
- amino acid
- target composition
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- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/44—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material not provided for elsewhere, e.g. haptens, metals, DNA, RNA, amino acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/35—Valency
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
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Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9636418B2 (en) | 2013-03-12 | 2017-05-02 | Amgen Inc. | Potent and selective inhibitors of NAV1.7 |
| US10344060B2 (en) * | 2013-03-12 | 2019-07-09 | Amgen Inc. | Potent and selective inhibitors of Nav1.7 |
| DK2968495T3 (da) * | 2013-03-15 | 2019-10-14 | Daniel J Capon | Hybrid immunoglobulin indeholdende en ikke-peptid-bro |
| LT3116486T (lt) | 2014-03-14 | 2020-04-10 | Biomolecular Holdings Llc | Hibridinis imunoglobulinas, turintis nepetidilinę jungtį |
| KR101981532B1 (ko) * | 2014-06-12 | 2019-09-02 | 라 파마슈티컬스 인코포레이티드 | 보체 활성의 조절 |
| CN105348392B (zh) * | 2015-11-18 | 2019-08-02 | 北京华金瑞清生物医药技术有限公司 | 一种Nav1.7抑制剂及其改造方法 |
| US20170239183A1 (en) * | 2016-02-23 | 2017-08-24 | PixarBio Corporation | COMPOSITIONS COMPRISING NAv1.7 SELECTIVE INHIBITORS FOR TREATING ACUTE, POST-OPERATIVE, OR CHRONIC PAIN AND METHODS OF USING THE SAME |
| EP3512870B1 (en) * | 2016-09-16 | 2022-08-03 | Olipass Corporation | Scn9a antisense oligonucleotides |
| RU2762293C2 (ru) * | 2017-01-24 | 2021-12-17 | Олипасс Корпорейшн | Антисмысловое для scn9a обезболивающее средство |
| CN109517041B (zh) * | 2018-11-14 | 2019-09-17 | 青海芬陀利华生物科技有限公司 | Gptx-1毒素及其应用 |
| CN116234920A (zh) * | 2020-08-05 | 2023-06-06 | 国立研究开发法人产业技术总合研究所 | 作用于靶蛋白的多肽的筛选方法 |
| US20230374084A1 (en) | 2020-09-23 | 2023-11-23 | Aldevron, Llc | Potent and selective inhibitors of nav1.7 |
| CN113429463B (zh) * | 2021-05-18 | 2022-08-23 | 湖南百尔泰克生物医药有限公司 | 一种具有镇痛作用的多肽及其应用 |
| CN114805491B (zh) * | 2022-03-15 | 2025-10-03 | 青岛海洋生物医药研究院 | 一种芋螺毒素kiiia突变体及其制备方法和应用 |
| CN114805492B (zh) * | 2022-03-15 | 2025-07-22 | 上海元炘执药科技有限公司 | 一种用于抑制电压门控钠离子通道1.4的芋螺毒素kiiia突变体及其制备方法和应用 |
| CN114917324B (zh) * | 2022-04-22 | 2025-05-30 | 江苏好上医生物医药有限公司 | 一种含虎纹毒素-iv的药物组合物及其应用 |
| KR20250005373A (ko) | 2022-04-22 | 2025-01-09 | 버텍스 파마슈티칼스 인코포레이티드 | 통증 치료를 위한 헤테로아릴 화합물 |
| EP4511115A1 (en) | 2022-04-22 | 2025-02-26 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| EP4511114A1 (en) | 2022-04-22 | 2025-02-26 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| AU2023255558A1 (en) | 2022-04-22 | 2024-10-31 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| CN120603815A (zh) | 2022-12-06 | 2025-09-05 | 沃泰克斯药物股份有限公司 | 钠通道的取代四氢呋喃调节剂的合成方法 |
| WO2025090480A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| TW202523313A (zh) | 2023-10-23 | 2025-06-16 | 美商維泰克斯製藥公司 | 用於治療疼痛之雜芳基化合物 |
| TW202535867A (zh) | 2023-10-23 | 2025-09-16 | 美商維泰克斯製藥公司 | 用於治療疼痛之鈉通道調節劑及其固體形式的製備方法 |
| WO2025090516A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Methods of preparing compounds for treating pain and solid forms thereof |
| US20250163168A1 (en) | 2023-11-17 | 2025-05-22 | Pfizer Inc. | Novel antibodies and antibody conjugates for the treatment of metabolic disorders |
| US20250186419A1 (en) | 2023-12-07 | 2025-06-12 | Vertex Pharmaceuticals Incorporated | Dosing regimens for treating pain |
| WO2025230491A1 (en) * | 2024-04-30 | 2025-11-06 | Vsy Biyoteknoloji Ve Ilac Sanayi Anonim Sirketi | A formulation for the treatment of interstitial cystitis disorder in particular |
Family Cites Families (132)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3691016A (en) | 1970-04-17 | 1972-09-12 | Monsanto Co | Process for the preparation of insoluble enzymes |
| CA1023287A (en) | 1972-12-08 | 1977-12-27 | Boehringer Mannheim G.M.B.H. | Process for the preparation of carrier-bound proteins |
| US4351337A (en) | 1973-05-17 | 1982-09-28 | Arthur D. Little, Inc. | Biodegradable, implantable drug delivery device, and process for preparing and using the same |
| US3941763A (en) | 1975-03-28 | 1976-03-02 | American Home Products Corporation | PGlu-D-Met-Trp-Ser-Tyr-D-Ala-Leu-Arg-Pro-Gly-NH2 and intermediates |
| US4195128A (en) | 1976-05-03 | 1980-03-25 | Bayer Aktiengesellschaft | Polymeric carrier bound ligands |
| US4083368A (en) | 1976-09-01 | 1978-04-11 | Freezer Winthrop J | Inhaler |
| US4330440A (en) | 1977-02-08 | 1982-05-18 | Development Finance Corporation Of New Zealand | Activated matrix and method of activation |
| CA1093991A (en) | 1977-02-17 | 1981-01-20 | Hideo Hirohara | Enzyme immobilization with pullulan gel |
| US4229537A (en) | 1978-02-09 | 1980-10-21 | New York University | Preparation of trichloro-s-triazine activated supports for coupling ligands |
| US5002936A (en) | 1985-04-12 | 1991-03-26 | Seymour Lieberman | Lipophilic complexes of pharmacologically active inorganic mineral acid esters of organic compounds |
| US5206344A (en) | 1985-06-26 | 1993-04-27 | Cetus Oncology Corporation | Interleukin-2 muteins and polymer conjugation thereof |
| US4925673A (en) | 1986-08-18 | 1990-05-15 | Clinical Technologies Associates, Inc. | Delivery systems for pharmacological agents encapsulated with proteinoids |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US5260203A (en) | 1986-09-02 | 1993-11-09 | Enzon, Inc. | Single polypeptide chain binding molecules |
| DE3785186T2 (de) | 1986-09-02 | 1993-07-15 | Enzon Lab Inc | Bindungsmolekuele mit einzelpolypeptidkette. |
| AU607172B2 (en) | 1986-12-22 | 1991-02-28 | Cygnus, Inc. | Diffusion matrix for transdermal drug administration |
| US4906169A (en) | 1986-12-29 | 1990-03-06 | Rutgers, The State University Of New Jersey | Transdermal estrogen/progestin dosage unit, system and process |
| US5023084A (en) | 1986-12-29 | 1991-06-11 | Rutgers, The State University Of New Jersey | Transdermal estrogen/progestin dosage unit, system and process |
| US4849224A (en) | 1987-11-12 | 1989-07-18 | Theratech Inc. | Device for administering an active agent to the skin or mucosa |
| US4983395A (en) | 1987-11-12 | 1991-01-08 | Theratech Inc. | Device for administering an active agent to the skin or mucosa |
| US4847325A (en) | 1988-01-20 | 1989-07-11 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
| DE68925893T2 (de) | 1988-07-23 | 1996-08-08 | Delta Biotechnology Ltd | Sekretorische leader-sequenzen |
| US4925677A (en) | 1988-08-31 | 1990-05-15 | Theratech, Inc. | Biodegradable hydrogel matrices for the controlled release of pharmacologically active agents |
| US4994439A (en) | 1989-01-19 | 1991-02-19 | California Biotechnology Inc. | Transmembrane formulations for drug administration |
| US5166322A (en) | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| US5171264A (en) | 1990-02-28 | 1992-12-15 | Massachusetts Institute Of Technology | Immobilized polyethylene oxide star molecules for bioapplications |
| US6552170B1 (en) | 1990-04-06 | 2003-04-22 | Amgen Inc. | PEGylation reagents and compounds formed therewith |
| JP3051145B2 (ja) | 1990-08-28 | 2000-06-12 | 住友製薬株式会社 | 新規なポリエチレングリコール誘導体修飾ペプチド |
| US5252714A (en) | 1990-11-28 | 1993-10-12 | The University Of Alabama In Huntsville | Preparation and use of polyethylene glycol propionaldehyde |
| ES2199935T3 (es) | 1991-03-15 | 2004-03-01 | Amgen Inc. | Pegilacion de polipeptidos. |
| JP3507486B2 (ja) | 1991-03-15 | 2004-03-15 | アムジエン・インコーポレーテツド | 顆粒球コロニー刺激因子の肺内投与 |
| AU3178993A (en) | 1991-11-25 | 1993-06-28 | Enzon, Inc. | Multivalent antigen-binding proteins |
| US5792451A (en) | 1994-03-02 | 1998-08-11 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
| JPH0640945A (ja) | 1992-07-23 | 1994-02-15 | Kureha Chem Ind Co Ltd | Fcフラグメント結合抗腫瘍剤 |
| WO1994008599A1 (en) | 1992-10-14 | 1994-04-28 | The Regents Of The University Of Colorado | Ion-pairing of drugs for improved efficacy and delivery |
| US5346701A (en) | 1993-02-22 | 1994-09-13 | Theratech, Inc. | Transmucosal delivery of macromolecular drugs |
| US5432155A (en) | 1993-06-29 | 1995-07-11 | The Salk Institute For Biological Studies | Conotoxins I |
| US5514774A (en) | 1993-06-29 | 1996-05-07 | University Of Utah Research Foundation | Conotoxin peptides |
| US5460820B1 (en) | 1993-08-03 | 1999-08-03 | Theratech Inc | Method for providing testosterone and optionally estrogen replacement therapy to women |
| US6342225B1 (en) | 1993-08-13 | 2002-01-29 | Deutshces Wollforschungsinstitut | Pharmaceutical active conjugates |
| US5643575A (en) | 1993-10-27 | 1997-07-01 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| US5919455A (en) | 1993-10-27 | 1999-07-06 | Enzon, Inc. | Non-antigenic branched polymer conjugates |
| US5446090A (en) | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
| AU1843295A (en) | 1994-02-23 | 1995-09-11 | Chiron Corporation | Method and compositions for increasing the serum half-life of pharmacologically active agents |
| FR2717688B1 (fr) | 1994-03-28 | 1996-07-05 | Lhd Lab Hygiene Dietetique | Système matriciel transdermique d'administration d'un oestrogène et/ou un progestatif à base d'EVA. |
| US5824784A (en) | 1994-10-12 | 1998-10-20 | Amgen Inc. | N-terminally chemically modified protein compositions and methods |
| CN1170360A (zh) | 1994-12-21 | 1998-01-14 | 瑟垃技术有限公司 | 具有粘性贴面和剥离密封圆片的经皮输送系统 |
| DE69530325T2 (de) | 1994-12-22 | 2004-02-19 | Astrazeneca Ab | Aerosol-arzneiformulierungen |
| US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| US5739277A (en) | 1995-04-14 | 1998-04-14 | Genentech Inc. | Altered polypeptides with increased half-life |
| US6096871A (en) | 1995-04-14 | 2000-08-01 | Genentech, Inc. | Polypeptides altered to contain an epitope from the Fc region of an IgG molecule for increased half-life |
| US5776896A (en) | 1996-01-03 | 1998-07-07 | Zeneca Limited | Analgesic peptides from venom of grammostola spatulata and use thereof |
| US5756663A (en) | 1996-01-03 | 1998-05-26 | Zeneca Limited | Antiarrhythmic peptide from venom of spider Grammostola spatulata |
| WO1997034631A1 (en) | 1996-03-18 | 1997-09-25 | Board Of Regents, The University Of Texas System | Immunoglobin-like domains with increased half lives |
| US5783208A (en) | 1996-07-19 | 1998-07-21 | Theratech, Inc. | Transdermal drug delivery matrix for coadministering estradiol and another steroid |
| US6077680A (en) | 1996-11-27 | 2000-06-20 | The University Of Florida | ShK toxin compositions and methods of use |
| DE69734451T2 (de) | 1996-12-26 | 2006-07-13 | Suntory Limited | Skorpion-spezifische neuropeptide |
| WO2000055371A1 (en) | 1999-03-18 | 2000-09-21 | Human Genome Sciences, Inc. | 27 human secreted proteins |
| US6548644B1 (en) | 1997-03-10 | 2003-04-15 | Immunex Corporation | Site protected protein modification |
| US5990237A (en) | 1997-05-21 | 1999-11-23 | Shearwater Polymers, Inc. | Poly(ethylene glycol) aldehyde hydrates and related polymers and applications in modifying amines |
| JP3530004B2 (ja) | 1998-02-06 | 2004-05-24 | 株式会社日立ユニシアオートモティブ | 吸入式投薬器 |
| US6022952A (en) | 1998-04-01 | 2000-02-08 | University Of Alberta | Compositions and methods for protein secretion |
| US6451986B1 (en) | 1998-06-22 | 2002-09-17 | Immunex Corporation | Site specific protein modification |
| AUPP589598A0 (en) | 1998-09-14 | 1998-10-08 | University Of Queensland, The | Novel peptides |
| US6660843B1 (en) | 1998-10-23 | 2003-12-09 | Amgen Inc. | Modified peptides as therapeutic agents |
| EP1132479B1 (en) | 1998-11-20 | 2009-04-22 | Fuso Pharmaceutical Industries Ltd. | Protein expression vector and utilization thereof |
| US6245740B1 (en) | 1998-12-23 | 2001-06-12 | Amgen Inc. | Polyol:oil suspensions for the sustained release of proteins |
| KR100491815B1 (ko) | 1998-12-23 | 2005-05-27 | 암젠 인코포레이티드 | 단백질의 서방성 수송을 위한 폴리올/오일 현탁액을 포함하는 제약학적 조성물 및 그것의 제조방법 |
| US6887470B1 (en) | 1999-09-10 | 2005-05-03 | Conjuchem, Inc. | Protection of endogenous therapeutic peptides from peptidase activity through conjugation to blood components |
| WO2001038564A2 (en) | 1999-11-26 | 2001-05-31 | Mcgill University | Loci for idiopathic generalized epilepsy, mutations thereof and method using same to assess, diagnose, prognose or treat epilepsy |
| CA2393616A1 (en) | 2000-01-31 | 2001-08-02 | Human Genome Sciences, Inc. | Nucleic acids, proteins, and antibodies |
| WO2001062827A2 (en) | 2000-02-22 | 2001-08-30 | Shearwater Corporation | N-maleimidyl polymer derivatives |
| SE0000935D0 (sv) | 2000-03-21 | 2000-03-21 | Astrazeneca Ab | An inhalation device |
| US7125847B1 (en) | 2000-04-07 | 2006-10-24 | The Research Foundation Of State University Of New York At Buffalo | Mechanically activated channel blocker |
| CN1133461C (zh) | 2000-04-11 | 2004-01-07 | 厦门北大之路生物工程有限公司 | 虎纹捕鸟蜘蛛毒素提取物在制备镇痛药物中的应用 |
| CA2405550A1 (en) | 2000-04-12 | 2001-10-25 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| EP1280895B1 (en) | 2000-05-10 | 2005-08-03 | Centre National De La Recherche Scientifique (Cnrs) | Polypeptide inhibiting a proton-gated na+ channel |
| EP1177806A1 (en) | 2000-08-04 | 2002-02-06 | The Technology Partnership Public Limited Company | Dry powder inhaler |
| GB0021617D0 (en) | 2000-09-02 | 2000-10-18 | Imp College Innovations Ltd | Diagnosis and treatment of cancer |
| JP5013152B2 (ja) | 2001-02-28 | 2012-08-29 | 株式会社ビーエムジー | 蛋白質複合体形成剤 |
| CA2440582A1 (en) | 2001-03-09 | 2002-10-03 | Dyax Corp. | Serum albumin binding moieties |
| US20050054051A1 (en) | 2001-04-12 | 2005-03-10 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| CA2443968A1 (en) | 2001-04-12 | 2002-10-24 | Imperial College Innovations Limited | Diagnosis and treatment of cancer: i |
| GB0120238D0 (en) | 2001-08-20 | 2001-10-10 | Univ College Of London | Sodium channel regulators and modulators |
| US6887487B2 (en) | 2001-10-19 | 2005-05-03 | Idexx Laboratories, Inc. | Injectable compositions for the controlled delivery of pharmacologically active compound |
| US6900317B2 (en) | 2002-02-19 | 2005-05-31 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Salts of the CGRP antagonist BIBN4096 and inhalable powdered medicaments containing them |
| US7125676B2 (en) | 2002-02-25 | 2006-10-24 | Vanderbilt University | Expression system for human brain-specific voltage-gated sodium channel, type 1 |
| US20030191056A1 (en) | 2002-04-04 | 2003-10-09 | Kenneth Walker | Use of transthyretin peptide/protein fusions to increase the serum half-life of pharmacologically active peptides/proteins |
| ATE469135T1 (de) | 2002-05-30 | 2010-06-15 | Scripps Research Inst | Kupferkatalysierte ligierung von aziden und acetylenen |
| GB0219512D0 (en) | 2002-08-21 | 2002-10-02 | Norton Healthcare Ltd | Inhalation compositions with high drug ratios |
| ATE447025T1 (de) | 2003-03-26 | 2009-11-15 | Pharmadesign Inc | Ionenkanalaktivität hemmende niedrigmolekulare peptide |
| ES2298785T3 (es) | 2003-06-12 | 2008-05-16 | Eli Lilly And Company | Proteinas de fusion. |
| AR045445A1 (es) | 2003-08-05 | 2005-10-26 | Vertex Pharma | Compuestos ihinibidores de canales ionicos regulados por voltaje |
| US7615563B2 (en) | 2003-08-08 | 2009-11-10 | Gonzalez Iii Jesus E | Compositions useful as inhibitors of voltage-gated sodium channels |
| TW200524888A (en) | 2003-08-08 | 2005-08-01 | Vertex Pharma | Compositions useful as inhibitors of voltage-gated ion channels |
| US7125908B2 (en) | 2003-08-29 | 2006-10-24 | Allergan, Inc. | Treating pain using selective antagonists of persistent sodium current |
| US7060723B2 (en) | 2003-08-29 | 2006-06-13 | Allergan, Inc. | Treating neurological disorders using selective antagonists of persistent sodium current |
| AU2005207002B2 (en) | 2004-01-21 | 2011-03-17 | University Of Utah Research Foundation | Mutant sodium channel Nav1.7 and methods related thereto |
| WO2005118614A1 (en) | 2004-04-08 | 2005-12-15 | Avigen, Inc. | Methods and compositions for treating neuropathic pain |
| US7323169B2 (en) | 2004-04-23 | 2008-01-29 | Amgen Inc. | Sustained release formulations |
| CN1973404B (zh) | 2004-06-23 | 2011-06-08 | 胡贝尔和茹纳股份公司 | 宽带贴片天线 |
| GB0414272D0 (en) | 2004-06-25 | 2004-07-28 | Cellpep Sa | OsK1 derivatives |
| US7259145B2 (en) | 2004-07-07 | 2007-08-21 | The Research Foundation Of State University Of New York | Mechanically activated channel blocker |
| WO2006036834A2 (en) | 2004-09-24 | 2006-04-06 | Amgen Inc. | MODIFIED Fc MOLECULES |
| EP1796709A4 (en) | 2004-10-07 | 2009-10-28 | Univ California | ANALOGUES OF TOXIN SHK AND USES IN SELECTIVE INHIBITION OF KV1.3 POTASSIUM CHANNELS |
| JP2008519034A (ja) | 2004-11-03 | 2008-06-05 | バーテックス ファーマシューティカルズ インコーポレイテッド | イオンチャネル調節剤としてのピリミジン誘導体および使用方法 |
| US20060199812A1 (en) | 2005-01-24 | 2006-09-07 | Amgen Inc. | Method of conjugating aminothiol containing molecules to vehicles |
| US7531523B2 (en) | 2005-02-17 | 2009-05-12 | Vertex Pharmaceuticals Incorporated | Sodium channel protein type III alpha-subunit splice variant |
| US7833979B2 (en) | 2005-04-22 | 2010-11-16 | Amgen Inc. | Toxin peptide therapeutic agents |
| GB0517487D0 (en) | 2005-08-26 | 2005-10-05 | Isis Innovation | Antibodies |
| US7972813B2 (en) | 2005-09-30 | 2011-07-05 | Vertex Pharmaceuticals Incorporated | Tetrodotoxin-resistant sodium channel alpha subunit |
| JP2009514545A (ja) | 2005-11-08 | 2009-04-09 | アテリス ラボラトリーズ | μ−コノトキシンぺプチドおよびμ−コノトキシンぺプチドの局所麻酔薬としての使用 |
| WO2007109324A2 (en) | 2006-03-21 | 2007-09-27 | Xenon Pharmaceuticals, Inc. | Potent and selective nav 1.7 sodium channel blockers |
| EP2628749A3 (en) | 2006-06-20 | 2013-12-04 | Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center | Antimicrobial kinocidin compostions and methods of use |
| JP4742345B2 (ja) * | 2006-06-20 | 2011-08-10 | 独立行政法人産業技術総合研究所 | カルシウムチャネルを遮断するグラモストラ・スパチュラタ由来のポリペプチドおよびその遺伝子 |
| WO2008088422A2 (en) | 2006-10-25 | 2008-07-24 | Amgen Inc. | Toxin peptide therapeutic agents |
| WO2009033027A2 (en) | 2007-09-05 | 2009-03-12 | Medtronic, Inc. | Suppression of scn9a gene expression and/or function for the treatment of pain |
| CN101480393A (zh) * | 2008-01-07 | 2009-07-15 | 云南昊邦制药有限公司 | 草乌甲素作为制备治疗Nav1.7疼痛病症药物的应用 |
| EP2249856B1 (en) | 2008-01-30 | 2013-11-06 | Baylor College Of Medicine | Peptides that target dorsal root ganglion neurons |
| BRPI0924225A2 (pt) | 2009-02-02 | 2016-10-11 | Chromocell Corp | linhagens de células que expressam nav e métodos de uso |
| WO2010104114A1 (ja) * | 2009-03-10 | 2010-09-16 | 独立行政法人産業技術総合研究所 | ポリペプチドライブラリーを調製する方法 |
| WO2010104115A1 (ja) | 2009-03-10 | 2010-09-16 | 独立行政法人産業技術総合研究所 | 膜タンパク質を特異的に認識するポリペプチドの調製方法 |
| CA2755133A1 (en) | 2009-03-20 | 2010-09-23 | Amgen Inc. | Selective and potent peptide inhibitors of kv1.3 |
| JP5555891B2 (ja) | 2009-09-15 | 2014-07-23 | アロモネ プリクリニカル リミテッド | クモ毒から単離した新規ペプチド及びその使用 |
| GB0922435D0 (en) | 2009-12-22 | 2010-02-03 | Ucb Pharma Sa | Method |
| GB0922434D0 (en) | 2009-12-22 | 2010-02-03 | Ucb Pharma Sa | antibodies and fragments thereof |
| WO2011051350A1 (en) | 2009-10-27 | 2011-05-05 | Ucb Pharma S.A. | Function modifying nav 1.7 antibodies |
| US8871996B2 (en) | 2010-06-09 | 2014-10-28 | Regeneron Pharmaceuticals, Inc. | Mice expressing human voltage-gated sodium channels |
| US9279003B2 (en) | 2010-07-07 | 2016-03-08 | Purdue Pharma L.P. | Analogs of sodium channel peptide toxin |
| EP2852397B1 (en) | 2012-05-18 | 2022-02-16 | Janssen Biotech, Inc. | Huwentoxin-iv variants and methods of use |
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2012
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- 2012-03-16 EA EA201391331A patent/EA201391331A1/ru unknown
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- 2012-03-16 WO PCT/US2012/029537 patent/WO2012125973A2/en not_active Ceased
- 2012-03-16 HK HK14111760.9A patent/HK1198173A1/xx unknown
- 2012-03-16 UY UY0001033959A patent/UY33959A/es not_active Application Discontinuation
- 2012-03-16 US US14/005,135 patent/US9340590B2/en active Active
- 2012-03-16 PE PE2013002050A patent/PE20140593A1/es not_active Application Discontinuation
- 2012-03-16 EP EP12711312.4A patent/EP2686340A2/en not_active Withdrawn
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- 2012-03-16 AP AP2013007173A patent/AP2013007173A0/xx unknown
- 2012-03-16 CA CA2830065A patent/CA2830065A1/en not_active Abandoned
- 2012-03-16 JP JP2013558223A patent/JP2014509859A/ja active Pending
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- 2012-03-16 BR BR112013023674A patent/BR112013023674A2/pt not_active IP Right Cessation
- 2012-03-16 KR KR1020137027301A patent/KR20140145947A/ko not_active Withdrawn
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2013
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- 2013-10-11 CO CO13242679A patent/CO6821886A2/es unknown
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2016
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| KR20140145947A (ko) | 2014-12-24 |
| HK1198173A1 (en) | 2015-03-13 |
| US9796766B2 (en) | 2017-10-24 |
| CL2013002673A1 (es) | 2014-07-25 |
| CA2830065A1 (en) | 2012-09-20 |
| PE20140593A1 (es) | 2014-05-10 |
| CN103930437A (zh) | 2014-07-16 |
| BR112013023674A2 (pt) | 2016-12-13 |
| US20140073577A1 (en) | 2014-03-13 |
| NZ615242A (en) | 2016-03-31 |
| SG193434A1 (en) | 2013-10-30 |
| AU2012228990B2 (en) | 2017-04-06 |
| JP2014509859A (ja) | 2014-04-24 |
| AR088413A1 (es) | 2014-06-11 |
| US20160304570A1 (en) | 2016-10-20 |
| CO6821886A2 (es) | 2013-12-31 |
| AU2012228990A1 (en) | 2013-09-19 |
| ZA201306920B (en) | 2014-05-28 |
| EP2686340A2 (en) | 2014-01-22 |
| CR20130533A (es) | 2014-01-09 |
| MA35385B1 (fr) | 2014-09-01 |
| SG10201601789TA (en) | 2016-04-28 |
| WO2012125973A2 (en) | 2012-09-20 |
| US9340590B2 (en) | 2016-05-17 |
| UY33959A (es) | 2012-09-28 |
| WO2012125973A3 (en) | 2013-01-03 |
| EA201391331A1 (ru) | 2014-02-28 |
| PH12013501865A1 (en) | 2014-01-06 |
| MX2013010497A (es) | 2013-12-16 |
| JP2017031157A (ja) | 2017-02-09 |
| AP2013007173A0 (en) | 2013-10-31 |
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