ES2262518T5 - Antagonistas de tek. - Google Patents
Antagonistas de tek. Download PDFInfo
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- ES2262518T5 ES2262518T5 ES00938207T ES00938207T ES2262518T5 ES 2262518 T5 ES2262518 T5 ES 2262518T5 ES 00938207 T ES00938207 T ES 00938207T ES 00938207 T ES00938207 T ES 00938207T ES 2262518 T5 ES2262518 T5 ES 2262518T5
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- tek
- polypeptide
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/71—Receptors; Cell surface antigens; Cell surface determinants for growth factors; for growth regulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
- C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
Landscapes
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- General Health & Medical Sciences (AREA)
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- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US13788999P | 1999-06-07 | 1999-06-07 | |
| US137889P | 1999-06-07 |
Publications (2)
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| ES2262518T3 ES2262518T3 (es) | 2006-12-01 |
| ES2262518T5 true ES2262518T5 (es) | 2009-05-08 |
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| ES00938207T Expired - Lifetime ES2262518T5 (es) | 1999-06-07 | 2000-06-07 | Antagonistas de tek. |
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| US (2) | US6413932B1 (https=) |
| EP (1) | EP1187918B9 (https=) |
| JP (1) | JP4587626B2 (https=) |
| AT (1) | ATE324444T1 (https=) |
| AU (1) | AU783960B2 (https=) |
| CA (1) | CA2374851A1 (https=) |
| CY (1) | CY1105078T1 (https=) |
| DE (1) | DE60027564T3 (https=) |
| DK (1) | DK1187918T4 (https=) |
| ES (1) | ES2262518T5 (https=) |
| IL (2) | IL146482A0 (https=) |
| NZ (1) | NZ516258A (https=) |
| PT (1) | PT1187918E (https=) |
| WO (1) | WO2000075323A1 (https=) |
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| EP1239869B1 (en) | 1999-12-20 | 2013-08-28 | Immunex Corporation | Tweak receptor |
| US20030064053A1 (en) * | 2001-08-31 | 2003-04-03 | Shengjiang Liu | Multivalent protein conjugate with multiple ligand-binding domains of receptors |
| US7138370B2 (en) | 2001-10-11 | 2006-11-21 | Amgen Inc. | Specific binding agents of human angiopoietin-2 |
| US7658924B2 (en) | 2001-10-11 | 2010-02-09 | Amgen Inc. | Angiopoietin-2 specific binding agents |
| US7205275B2 (en) * | 2001-10-11 | 2007-04-17 | Amgen Inc. | Methods of treatment using specific binding agents of human angiopoietin-2 |
| US7521053B2 (en) * | 2001-10-11 | 2009-04-21 | Amgen Inc. | Angiopoietin-2 specific binding agents |
| CN1315536C (zh) * | 2002-09-13 | 2007-05-16 | 李进 | 肿瘤抗原疫苗及其制备方法和疫苗组合物 |
| US20050239088A1 (en) * | 2003-05-16 | 2005-10-27 | Shepard H M | Intron fusion proteins, and methods of identifying and using same |
| KR101254371B1 (ko) | 2003-07-18 | 2013-05-02 | 암젠 프레몬트 인코포레이티드 | 간세포 성장인자에 결합하는 분리된 항체 |
| JP2008506366A (ja) * | 2004-05-14 | 2008-03-06 | レセプター バイオロジックス インコーポレイテッド | 細胞表面受容体アイソフォームならびにその同定および使用方法 |
| AU2005259537A1 (en) * | 2004-06-25 | 2006-01-12 | Licentia, Ltd. | Tie receptor and tie ligand materials and methods for modulating female fertility |
| US7507748B2 (en) * | 2004-07-22 | 2009-03-24 | Amgen Inc. | Substituted aryl-amine derivatives and methods of use |
| US20080119367A1 (en) * | 2004-12-17 | 2008-05-22 | Mayo Foundation For Medical Education And Research | Prognosis of Renal Cell Carcinoma |
| BRPI0519596B1 (pt) * | 2004-12-21 | 2022-01-18 | Astrazeneca Ab | Agente de ligação alvejado, anticorpo monoclonal que se liga a angiopoietina-2, molécula de ácido nucleico, vetor, e, uso do agente de ligação alvejado |
| US20090170769A1 (en) * | 2005-05-13 | 2009-07-02 | Pei Jin | Cell surface receptor isoforms and methods of identifying and using the same |
| AR059066A1 (es) | 2006-01-27 | 2008-03-12 | Amgen Inc | Combinaciones del inhibidor de la angiopoyetina -2 (ang2) y el inhibidor del factor de crecimiento endotelial vascular (vegf) |
| PE20080403A1 (es) | 2006-07-14 | 2008-04-25 | Amgen Inc | Derivados heterociclicos fusionados y metodos de uso |
| US8217177B2 (en) | 2006-07-14 | 2012-07-10 | Amgen Inc. | Fused heterocyclic derivatives and methods of use |
| AU2008219166B2 (en) | 2007-02-16 | 2013-05-16 | Amgen Inc. | Nitrogen-containing heterocyclyl ketones and their use as c-Met inhibitors |
| ES2650224T3 (es) | 2007-08-21 | 2018-01-17 | Amgen, Inc. | Proteínas de unión al antígeno C-FMS humano |
| US8557242B2 (en) | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | ERBB2 antibodies comprising modular recognition domains |
| CA2711256C (en) | 2008-01-03 | 2019-01-15 | The Scripps Research Institute | Antibody targeting through a modular recognition domain |
| US8574577B2 (en) | 2008-01-03 | 2013-11-05 | The Scripps Research Institute | VEGF antibodies comprising modular recognition domains |
| US8454960B2 (en) | 2008-01-03 | 2013-06-04 | The Scripps Research Institute | Multispecific antibody targeting and multivalency through modular recognition domains |
| US8557243B2 (en) | 2008-01-03 | 2013-10-15 | The Scripps Research Institute | EFGR antibodies comprising modular recognition domains |
| AU2009209251B8 (en) | 2008-01-28 | 2015-03-26 | Medimmune Limited | Stabilized Angiopoietin-2 antibodies and uses thereof |
| JO2913B1 (en) | 2008-02-20 | 2015-09-15 | امجين إنك, | Antibodies directed towards angiopoietin-1 and angiopoietin-2 proteins and their uses |
| EP2307456B1 (en) | 2008-06-27 | 2014-10-15 | Amgen Inc. | Ang-2 inhibition to treat multiple sclerosis |
| US20120100166A1 (en) | 2010-07-15 | 2012-04-26 | Zyngenia, Inc. | Ang-2 Binding Complexes and Uses Thereof |
| CN103703000B (zh) | 2011-03-23 | 2015-11-25 | 安姆根有限公司 | Cdk4/6和flt3的稠合三环双重抑制剂 |
| EP2714738B1 (en) | 2011-05-24 | 2018-10-10 | Zyngenia, Inc. | Multivalent and monovalent multispecific complexes and their uses |
| US9745288B2 (en) | 2011-08-16 | 2017-08-29 | Indiana University Research And Technology Corporation | Compounds and methods for treating cancer by inhibiting the urokinase receptor |
| CA2844306C (en) | 2011-08-19 | 2022-08-16 | Regeneron Pharmaceuticals, Inc. | Anti-tie2 antibodies and uses thereof |
| US10316105B2 (en) | 2011-08-19 | 2019-06-11 | Regeneron Pharmaceuticals, Inc. | Anti-TIE2 antibodies and uses thereof |
| AR090263A1 (es) | 2012-03-08 | 2014-10-29 | Hoffmann La Roche | Terapia combinada de anticuerpos contra el csf-1r humano y las utilizaciones de la misma |
| WO2014036022A1 (en) | 2012-08-29 | 2014-03-06 | Amgen Inc. | Quinazolinone compounds and derivatives thereof |
| GB201223053D0 (en) | 2012-12-20 | 2013-02-06 | Medical Res Council | Receptor |
| BR112015023752B1 (pt) | 2013-03-15 | 2023-11-14 | Zyngenia, Inc. | Domínio de reconhecimento modular (mrd), complexo compreendendo mrd e cetuximabe, usos do complexo para inibir a angiogênese e tratar câncer e composição farmacêutica compreendendo o dito complexo |
| TW201605896A (zh) | 2013-08-30 | 2016-02-16 | 安美基股份有限公司 | Gitr抗原結合蛋白 |
| UA126115C2 (uk) | 2016-03-08 | 2022-08-17 | Янссен Байотек, Інк. | Антитіло до gitr |
| US20190292254A1 (en) | 2016-07-14 | 2019-09-26 | Scholar Rock, Inc. | TGFBeta Antibodies, Methods and Uses |
| WO2018119183A2 (en) | 2016-12-22 | 2018-06-28 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| EA201992781A1 (ru) | 2017-05-22 | 2020-04-01 | Эмджен Инк. | Ингибиторы g12c kras и способы их применения |
| MA50077A (fr) | 2017-09-08 | 2020-07-15 | Amgen Inc | Inhibiteurs de kras g12c et leurs procédés d'utilisation |
| WO2019213516A1 (en) | 2018-05-04 | 2019-11-07 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| ES2995514T3 (en) | 2018-05-04 | 2025-02-10 | Amgen Inc | Kras g12c inhibitors and methods of using the same |
| EP3790886B1 (en) | 2018-05-10 | 2024-06-26 | Amgen Inc. | Kras g12c inhibitors for the treatment of cancer |
| ES2938987T3 (es) | 2018-06-01 | 2023-04-18 | Amgen Inc | Inhibidores de KRAS G12c y métodos de uso de los mismos |
| US20190375749A1 (en) | 2018-06-11 | 2019-12-12 | Amgen Inc. | Kras g12c inhibitors and methods of using the same |
| ES3060664T3 (en) | 2018-06-12 | 2026-03-27 | Amgen Inc | Kras g12c inhibitors encompassing a piperazine ring and use thereof in the treatment of cancer |
| CN108888756A (zh) * | 2018-07-25 | 2018-11-27 | 韩曙 | C16多肽和血管生成素Ang1的应用和应用二者的药物 |
| JP7516029B2 (ja) | 2018-11-16 | 2024-07-16 | アムジエン・インコーポレーテツド | Kras g12c阻害剤化合物の重要な中間体の改良合成法 |
| US11053226B2 (en) | 2018-11-19 | 2021-07-06 | Amgen Inc. | KRAS G12C inhibitors and methods of using the same |
| JP7377679B2 (ja) | 2018-11-19 | 2023-11-10 | アムジエン・インコーポレーテツド | がん治療のためのkrasg12c阻害剤及び1種以上の薬学的に活性な追加の薬剤を含む併用療法 |
| WO2020132651A1 (en) | 2018-12-20 | 2020-06-25 | Amgen Inc. | Kif18a inhibitors |
| EP3898616B1 (en) | 2018-12-20 | 2024-10-02 | Amgen Inc. | Heteroaryl amides useful as kif18a inhibitors |
| JP7676308B2 (ja) | 2018-12-20 | 2025-05-14 | アムジエン・インコーポレーテツド | Kif18a阻害剤として有用なヘテロアリールアミド |
| TWI844602B (zh) | 2018-12-20 | 2024-06-11 | 美商安進公司 | Kif18a抑制劑 |
| CN113727758A (zh) | 2019-03-01 | 2021-11-30 | 锐新医药公司 | 双环杂环基化合物及其用途 |
| WO2020180768A1 (en) | 2019-03-01 | 2020-09-10 | Revolution Medicines, Inc. | Bicyclic heteroaryl compounds and uses thereof |
| EP3738593A1 (en) | 2019-05-14 | 2020-11-18 | Amgen, Inc | Dosing of kras inhibitor for treatment of cancers |
| NZ782284A (en) | 2019-05-21 | 2024-11-29 | Amgen Inc | Solid state forms |
| CR20210687A (es) * | 2019-06-25 | 2022-03-03 | Gilead Sciences Inc | PROTEÍNAS DE FUSIÓN FLT3L-Fc Y MÉTODOS DE USO |
| EP4007756B1 (en) | 2019-08-02 | 2025-12-24 | Amgen Inc. | Kif18a inhibitors |
| US12540129B2 (en) | 2019-08-02 | 2026-02-03 | Amgen Inc. | KIF18A inhibitors |
| AU2020326627B2 (en) | 2019-08-02 | 2026-01-29 | Amgen Inc. | KIF18A inhibitors |
| WO2021026099A1 (en) | 2019-08-02 | 2021-02-11 | Amgen Inc. | Kif18a inhibitors |
| EP4031542B1 (en) | 2019-09-18 | 2025-10-15 | Merck Sharp & Dohme LLC | Small molecule inhibitors of kras g12c mutant |
| EP4684786A3 (en) | 2019-10-24 | 2026-04-08 | Amgen Inc. | Pyridopyrimidine derivatives useful as kras g12c and kras g12d inhibitors in the treatment of cancer |
| CN114867726B (zh) | 2019-10-28 | 2023-11-28 | 默沙东有限责任公司 | Kras g12c突变体的小分子抑制剂 |
| WO2021085653A1 (en) | 2019-10-31 | 2021-05-06 | Taiho Pharmaceutical Co., Ltd. | 4-aminobut-2-enamide derivatives and salts thereof |
| CN120699039A (zh) | 2019-11-04 | 2025-09-26 | 锐新医药公司 | Ras抑制剂 |
| WO2021091956A1 (en) | 2019-11-04 | 2021-05-14 | Revolution Medicines, Inc. | Ras inhibitors |
| MX2022005359A (es) | 2019-11-04 | 2022-06-02 | Revolution Medicines Inc | Inhibidores de ras. |
| TW202128688A (zh) | 2019-11-08 | 2021-08-01 | 美商銳新醫藥公司 | 雙環雜芳基化合物及其用途 |
| JP2023501528A (ja) | 2019-11-14 | 2023-01-18 | アムジエン・インコーポレーテツド | Kras g12c阻害剤化合物の改善された合成 |
| WO2021097207A1 (en) | 2019-11-14 | 2021-05-20 | Amgen Inc. | Improved synthesis of kras g12c inhibitor compound |
| EP4065231A1 (en) | 2019-11-27 | 2022-10-05 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| WO2021106231A1 (en) | 2019-11-29 | 2021-06-03 | Taiho Pharmaceutical Co., Ltd. | A compound having inhibitory activity against kras g12d mutation |
| WO2021126799A1 (en) | 2019-12-18 | 2021-06-24 | Merck Sharp & Dohme Corp. | Macrocyclic peptides as potent inhibitors of k-ras g12d mutant |
| CN114929279A (zh) | 2020-01-07 | 2022-08-19 | 锐新医药公司 | Shp2抑制剂给药和治疗癌症的方法 |
| WO2021215545A1 (en) | 2020-04-24 | 2021-10-28 | Taiho Pharmaceutical Co., Ltd. | Anticancer combination therapy with n-(1-acryloyl-azetidin-3-yl)-2-((1h-indazol-3-yl)amino)methyl)-1h-imidazole-5-carboxamide inhibitor of kras-g12c |
| WO2021215544A1 (en) | 2020-04-24 | 2021-10-28 | Taiho Pharmaceutical Co., Ltd. | Kras g12d protein inhibitors |
| IL299131A (en) | 2020-06-18 | 2023-02-01 | Revolution Medicines Inc | Methods for delaying, preventing and treating acquired resistance to RAS inhibitors |
| EP4183395A4 (en) | 2020-07-15 | 2024-07-24 | Taiho Pharmaceutical Co., Ltd. | PYRIMIDINE COMPOUND-CONTAINING COMBINATION FOR USE IN TUMOR TREATMENT |
| MX2023002248A (es) | 2020-09-03 | 2023-05-16 | Revolution Medicines Inc | Uso de inhibidores de sos1 para tratar neoplasias malignas con mutaciones de shp2. |
| MX2023003060A (es) | 2020-09-15 | 2023-04-05 | Revolution Medicines Inc | Derivados indolicos como inhibidores de ras en el tratamiento del cancer. |
| US20240051956A1 (en) | 2020-12-22 | 2024-02-15 | Qilu Regor Therapeutics Inc. | Sos1 inhibitors and uses thereof |
| AU2022238571A1 (en) | 2021-03-18 | 2023-09-14 | Seagen Inc. | Selective drug release from internalized conjugates of biologically active compounds |
| CA3217393A1 (en) | 2021-05-05 | 2022-11-10 | Elena S. Koltun | Ras inhibitors |
| AU2022268962A1 (en) | 2021-05-05 | 2023-12-14 | Revolution Medicines, Inc. | Ras inhibitors for the treatment of cancer |
| WO2022235866A1 (en) | 2021-05-05 | 2022-11-10 | Revolution Medicines, Inc. | Covalent ras inhibitors and uses thereof |
| WO2022250170A1 (en) | 2021-05-28 | 2022-12-01 | Taiho Pharmaceutical Co., Ltd. | Small molecule inhibitors of kras mutated proteins |
| AR127308A1 (es) | 2021-10-08 | 2024-01-10 | Revolution Medicines Inc | Inhibidores ras |
| WO2023064058A1 (en) | 2021-10-12 | 2023-04-20 | Peloton Therapeutics Inc. | Tricyclic sultams and sulfamides as antitumor agents |
| TW202340214A (zh) | 2021-12-17 | 2023-10-16 | 美商健臻公司 | 做為shp2抑制劑之吡唑并吡𠯤化合物 |
| EP4227307A1 (en) | 2022-02-11 | 2023-08-16 | Genzyme Corporation | Pyrazolopyrazine compounds as shp2 inhibitors |
| WO2023172858A1 (en) | 2022-03-07 | 2023-09-14 | Amgen Inc. | A process for preparing 4-methyl-2-propan-2-yl-pyridine-3-carbonitrile |
| CN119136806A (zh) | 2022-03-08 | 2024-12-13 | 锐新医药公司 | 用于治疗免疫难治性肺癌的方法 |
| WO2023240263A1 (en) | 2022-06-10 | 2023-12-14 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| AU2023358792A1 (en) | 2022-10-14 | 2025-04-17 | Black Diamond Therapeutics, Inc. | Methods of treating cancers using isoquinoline or 6-aza-quinoline derivatives |
| EP4687905A1 (en) | 2023-03-30 | 2026-02-11 | Revolution Medicines, Inc. | Compositions for inducing ras gtp hydrolysis and uses thereof |
| KR20260005904A (ko) | 2023-04-07 | 2026-01-12 | 레볼루션 메디슨즈, 인크. | 매크로사이클릭 ras 억제제 |
| CN121263418A (zh) | 2023-04-07 | 2026-01-02 | 锐新医药公司 | 大环ras抑制剂 |
| AU2024252105A1 (en) | 2023-04-14 | 2025-10-16 | Revolution Medicines, Inc. | Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof |
| KR20250172857A (ko) | 2023-04-14 | 2025-12-09 | 레볼루션 메디슨즈, 인크. | Ras 억제제의 결정형 |
| AU2024265078A1 (en) | 2023-05-04 | 2025-12-11 | Revolution Medicines, Inc. | Combination therapy for a ras related disease or disorder |
| IL326136A (en) | 2023-08-07 | 2026-03-01 | Revolution Medicines Inc | RMC-6291 for use in the treatment of a disease or disorder associated with the RAS protein |
| KR20260042550A (ko) | 2023-08-24 | 2026-03-31 | 다이호야쿠힌고교 가부시키가이샤 | 세다주리딘 및 아자시티딘의 고정 용량 조합물 |
| US20250154171A1 (en) | 2023-10-12 | 2025-05-15 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025085748A1 (en) | 2023-10-20 | 2025-04-24 | Merck Sharp & Dohme Llc | Small molecule inhibitors of kras proteins |
| TW202542151A (zh) | 2023-12-22 | 2025-11-01 | 美商銳格醫藥有限公司 | Sos1抑制劑及其用途 |
| TW202602929A (zh) | 2024-03-21 | 2026-01-16 | 美商思進公司 | Cd25抗體、抗體-藥物共軛體及彼等之用途 |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
| US20250375445A1 (en) | 2024-06-07 | 2025-12-11 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025265060A1 (en) | 2024-06-21 | 2025-12-26 | Revolution Medicines, Inc. | Therapeutic compositions and methods for managing treatment-related effects |
| WO2026006747A1 (en) | 2024-06-28 | 2026-01-02 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026015790A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015801A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015796A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015825A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Use of ras inhibitor for treating pancreatic cancer |
| WO2026050446A1 (en) | 2024-08-29 | 2026-03-05 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026072904A2 (en) | 2024-09-26 | 2026-04-02 | Revolution Medicines, Inc. | Compositions and methods for treating lung cancer |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2147729T3 (es) * | 1991-01-31 | 2000-10-01 | Cor Therapeutics Inc | Dominios de la region extracelular de polipeptidos receptores de factor de crecimiento derivado de plaquetas humano. |
| JPH07506242A (ja) | 1992-01-09 | 1995-07-13 | ヘルシンキ ユニバーシティ ホルディング リミテッド | Tie,新規内皮細胞受容体チロシンキナーゼ |
| US5955291A (en) | 1992-01-09 | 1999-09-21 | Alitalo; Kari | Antibodies recognizing tie receptor tyrosine kinase and uses thereof |
| WO1994000469A1 (en) * | 1992-06-26 | 1994-01-06 | Immunex Corporation | Novel tyrosine kinase |
| US5681714A (en) | 1992-07-30 | 1997-10-28 | Mount Sinai Hospital Corporation | Nucleic acid encoding tek receptor tyrosine kinase |
| JPH06315382A (ja) | 1993-05-06 | 1994-11-15 | Toshio Suda | Tie−2受容体をコードするdna及びtie−2受容体 |
| AU8143094A (en) * | 1993-11-12 | 1995-05-29 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | (tie-2), a novel receptor tyrosine kinase |
| AUPM379494A0 (en) | 1994-02-10 | 1994-03-03 | Ludwig Institute For Cancer Research | Immunointeractive molecules - ii |
| US5814464A (en) | 1994-10-07 | 1998-09-29 | Regeneron Pharma | Nucleic acids encoding TIE-2 ligand-2 |
| NZ328371A (en) | 1994-12-23 | 1999-05-28 | Ludwig Inst Cancer Res | Method of detecting a ligand capable of binding the receptor protein neuroepithelial tyrosine kinase (nyk) and its use in therapeutic compositions |
| WO1996031598A1 (en) | 1995-04-06 | 1996-10-10 | Regeneron Pharmaceuticals, Inc. | Tie-2 ligands, methods of making and uses thereof |
| US6033903A (en) * | 1995-06-02 | 2000-03-07 | Applied Research Systems, ARS Holding N.V. | Method of expressing and secreting soluble extracellular domains of human gonadotropin hormone receptors |
| US6306395B1 (en) * | 1996-05-02 | 2001-10-23 | Mochida Pharmaceutical Co., Ltd. | Fas antigen derivatives |
| AU5154098A (en) | 1996-10-31 | 1998-05-22 | Duke University | Soluble tie2 receptor |
| US6376653B1 (en) | 1998-09-28 | 2002-04-23 | Smithkline Beecham Plc | Tie2 antagonist antibodies |
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2000
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- 2000-06-07 JP JP2001502586A patent/JP4587626B2/ja not_active Expired - Fee Related
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| CY1105078T1 (el) | 2009-11-04 |
| US6413932B1 (en) | 2002-07-02 |
| IL146482A0 (en) | 2002-07-25 |
| NZ516258A (en) | 2004-02-27 |
| JP2003501090A (ja) | 2003-01-14 |
| JP4587626B2 (ja) | 2010-11-24 |
| EP1187918A1 (en) | 2002-03-20 |
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