AU2010300747A1 - Treating Notch1-antagonist-resistant cancer (s) using Notch3 antagonists - Google Patents
Treating Notch1-antagonist-resistant cancer (s) using Notch3 antagonists Download PDFInfo
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| PCT/US2010/050610 WO2011041336A2 (en) | 2009-09-30 | 2010-09-29 | Methods of treating cancer using notch antagonists |
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| AU2010300747A1 true AU2010300747A1 (en) | 2012-04-26 |
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Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2133796C1 (ru) * | 1997-10-09 | 1999-07-27 | ОАО "Томский электромеханический завод им.В.В.Вахрушева" | Люк смотрового колодца |
| JP2009539403A (ja) | 2006-06-13 | 2009-11-19 | オンコメッド ファーマシューティカルズ インコーポレイテッド | 癌を診断および処置するための組成物および方法 |
| US8088617B2 (en) | 2007-01-24 | 2012-01-03 | Oncomed Pharmaceuticals, Inc. | Antibodies that bind the glutamate ligand binding region of Notch1 |
| PE20090321A1 (es) * | 2007-06-04 | 2009-04-20 | Genentech Inc | Anticuerpos anti-notch1 nrr, metodo de preparacion y composicion farmaceutica |
| CA2729306C (en) | 2008-07-08 | 2015-08-18 | Oncomed Pharmaceuticals, Inc. | Notch-binding agents and antagonists and methods of use thereof |
| US9132189B2 (en) | 2008-07-08 | 2015-09-15 | Oncomed Pharmaceuticals, Inc. | Notch1 binding agents and methods of use thereof |
| RU2011151287A (ru) | 2009-06-18 | 2013-07-27 | Пфайзер Инк. | АНТИ Notch-1 АНТИТЕЛА |
| KR101580726B1 (ko) | 2010-12-15 | 2015-12-29 | 와이어쓰 엘엘씨 | 항-노치1 항체 |
| MX2015005810A (es) | 2012-11-07 | 2015-09-23 | Pfizer | Anticuerpos anti-notch y conjugados de anticuerpo-farmaco. |
| US9879083B2 (en) | 2012-12-19 | 2018-01-30 | Aveo Pharmaceuticals, Inc. | Anti-Notch3 antibodies |
| WO2014159242A1 (en) * | 2013-03-14 | 2014-10-02 | Novartis Ag | Notch 3 mutants and uses thereof |
| CN105246916A (zh) * | 2013-03-14 | 2016-01-13 | 诺华股份有限公司 | 针对notch 3的抗体 |
| MX2015011386A (es) * | 2013-03-15 | 2016-02-03 | Oncomed Pharm Inc | Metodo para tratar cancer pancreatico. |
| CN105764502A (zh) | 2013-07-26 | 2016-07-13 | 现代化制药公司 | 改善比生群及其类似物及衍生物的治疗益处的组合方法 |
| CA2936565C (en) | 2014-02-12 | 2020-08-11 | Genentech, Inc. | Anti-jagged1 antibodies and methods of use |
| BR112017000130A2 (pt) | 2014-07-11 | 2018-01-09 | Genentech Inc | método para atenuar a toxicidade associada à inibição da via de notch e método de tratamento do câncer |
| CN105585636B (zh) * | 2015-11-24 | 2020-03-03 | 南方医科大学 | 一种人NOTCH1 NICD蛋白Ser2162位点磷酸化抗体及其制备方法和应用 |
| ES2931955T3 (es) | 2016-04-29 | 2023-01-05 | Aveo Pharmaceuticals Inc | Anticuerpo anti-Notch3 |
| WO2024229406A1 (en) | 2023-05-04 | 2024-11-07 | Revolution Medicines, Inc. | Combination therapy for a ras related disease or disorder |
| US20250049810A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| US20250154171A1 (en) | 2023-10-12 | 2025-05-15 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025255438A1 (en) | 2024-06-07 | 2025-12-11 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
| GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| EP1690935A3 (en) | 1990-01-12 | 2008-07-30 | Abgenix, Inc. | Generation of xenogeneic antibodies |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US5661016A (en) | 1990-08-29 | 1997-08-26 | Genpharm International Inc. | Transgenic non-human animals capable of producing heterologous antibodies of various isotypes |
| US5633425A (en) | 1990-08-29 | 1997-05-27 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| JP2938569B2 (ja) | 1990-08-29 | 1999-08-23 | ジェンファーム インターナショナル，インコーポレイティド | 異種免疫グロブリンを作る方法及びトランスジェニックマウス |
| US5545806A (en) | 1990-08-29 | 1996-08-13 | Genpharm International, Inc. | Ransgenic non-human animals for producing heterologous antibodies |
| US5625126A (en) | 1990-08-29 | 1997-04-29 | Genpharm International, Inc. | Transgenic non-human animals for producing heterologous antibodies |
| GB9114948D0 (en) | 1991-07-11 | 1991-08-28 | Pfizer Ltd | Process for preparing sertraline intermediates |
| DE69637481T2 (de) | 1995-04-27 | 2009-04-09 | Amgen Fremont Inc. | Aus immunisierten Xenomäusen stammende menschliche Antikörper gegen IL-8 |
| EP0823941A4 (en) | 1995-04-28 | 2001-09-19 | Abgenix Inc | HUMAN ANTIBODIES DERIVED FROM IMMUNIZED XENO MOUSES |
| ES2301183T3 (es) | 1996-12-03 | 2008-06-16 | Amgen Fremont Inc. | Anticuerpo completamente humano que se une al receptor del egfr. |
| ATE531812T1 (de) | 1997-12-05 | 2011-11-15 | Scripps Research Inst | Humanisierung von nager-antikörpern |
| US20080181888A1 (en) | 2004-12-31 | 2008-07-31 | Ambrose Christine M | Polypeptides That Bind Br3 and Uses Thereof |
| CL2007002989A1 (es) | 2006-10-19 | 2008-05-16 | Genentech Inc | Anticuerpos anti-notch3; acido nucleico que los codifica; vector y celula que lo comprende; metodo de produccion; y su uso para el diagnostico de enfermedades relacionadas con notch3. |
| RU2461569C2 (ru) | 2006-10-19 | 2012-09-20 | Дженентек, Инк. | Агонистические антитела против notch3 и их применение для лечения notch3-ассоциированных заболеваний |
| KR101568049B1 (ko) | 2006-12-18 | 2015-11-11 | 제넨테크, 인크. | 항-ｎｏｔｃｈ3 길항제 항체 및 ｎｏｔｃｈ3-관련 질환의 예방 및 치료에 있어서 그의 용도 |
| US8088617B2 (en) * | 2007-01-24 | 2012-01-03 | Oncomed Pharmaceuticals, Inc. | Antibodies that bind the glutamate ligand binding region of Notch1 |
| EP2134356A2 (en) * | 2007-03-05 | 2009-12-23 | Board of Regents, The University of Texas System | Negative genetic regulation of cancer cell renewal in synergy with notch- or numb-specific immunotherapy |
| PE20090321A1 (es) | 2007-06-04 | 2009-04-20 | Genentech Inc | Anticuerpos anti-notch1 nrr, metodo de preparacion y composicion farmaceutica |
| CA2729306C (en) * | 2008-07-08 | 2015-08-18 | Oncomed Pharmaceuticals, Inc. | Notch-binding agents and antagonists and methods of use thereof |
| WO2010141249A2 (en) * | 2009-06-02 | 2010-12-09 | Merck Sharp & Dohme Corp. | Generation, characterization and uses thereof of anti-notch3 antibodies |
| RU2011151287A (ru) * | 2009-06-18 | 2013-07-27 | Пфайзер Инк. | АНТИ Notch-1 АНТИТЕЛА |
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2010
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- 2010-09-29 EP EP10762827.3A patent/EP2483311B1/en active Active
- 2010-09-29 AU AU2010300747A patent/AU2010300747A1/en not_active Abandoned
- 2010-09-29 MA MA34797A patent/MA33973B1/fr unknown
- 2010-09-29 PE PE2012000413A patent/PE20120998A1/es not_active Application Discontinuation
- 2010-09-29 PH PH1/2012/500574A patent/PH12012500574A1/en unknown
- 2010-09-29 ES ES10762827.3T patent/ES2580229T3/es active Active
- 2010-09-29 MX MX2012003851A patent/MX342250B/es active IP Right Grant
- 2010-09-29 JP JP2012532248A patent/JP6025563B2/ja active Active
- 2010-09-29 BR BR112012007252-8A patent/BR112012007252A2/pt not_active IP Right Cessation
- 2010-09-29 KR KR1020127010886A patent/KR101782180B1/ko not_active Expired - Fee Related
- 2010-09-29 CN CN201080054108.9A patent/CN102630229B/zh active Active
- 2010-09-29 CA CA2775880A patent/CA2775880A1/en not_active Abandoned
- 2010-09-29 WO PCT/US2010/050610 patent/WO2011041336A2/en not_active Ceased
- 2010-09-29 US US13/498,560 patent/US9200071B2/en active Active
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2012
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- 2012-03-16 ZA ZA2012/01984A patent/ZA201201984B/en unknown
- 2012-03-30 CL CL2012000800A patent/CL2012000800A1/es unknown
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- 2012-04-26 CR CR20120213A patent/CR20120213A/es unknown
- 2012-04-30 EC ECSP12011858 patent/ECSP12011858A/es unknown
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2015
- 2015-01-23 JP JP2015011573A patent/JP2015145362A/ja not_active Withdrawn
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2016
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Also Published As
| Publication number | Publication date |
|---|---|
| RU2012117619A (ru) | 2013-11-10 |
| ECSP12011858A (es) | 2012-06-29 |
| KR20120100952A (ko) | 2012-09-12 |
| EP2483311A2 (en) | 2012-08-08 |
| IL218662A0 (en) | 2012-05-31 |
| CN102630229A (zh) | 2012-08-08 |
| JP2017014219A (ja) | 2017-01-19 |
| JP2013506675A (ja) | 2013-02-28 |
| MA33973B1 (fr) | 2013-02-01 |
| JP2015145362A (ja) | 2015-08-13 |
| JP6025563B2 (ja) | 2016-11-16 |
| BR112012007252A2 (pt) | 2020-08-11 |
| US9200071B2 (en) | 2015-12-01 |
| US20120328608A1 (en) | 2012-12-27 |
| ES2580229T3 (es) | 2016-08-22 |
| PE20120998A1 (es) | 2012-08-14 |
| KR101782180B1 (ko) | 2017-10-23 |
| CR20120213A (es) | 2012-07-09 |
| EP2483311B1 (en) | 2016-05-18 |
| ZA201201984B (en) | 2013-05-29 |
| CN102630229B (zh) | 2015-03-04 |
| CA2775880A1 (en) | 2011-04-07 |
| PH12012500574A1 (en) | 2012-10-22 |
| WO2011041336A2 (en) | 2011-04-07 |
| HK1170505A1 (en) | 2013-03-01 |
| WO2011041336A3 (en) | 2012-05-03 |
| MX342250B (es) | 2016-09-22 |
| CL2012000800A1 (es) | 2012-08-31 |
| CO6531430A2 (es) | 2012-09-28 |
| MX2012003851A (es) | 2012-05-08 |
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