DE69832178T3 - Trail bindender rezeptor - Google Patents
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- DE69832178T3 DE69832178T3 DE69832178T DE69832178T DE69832178T3 DE 69832178 T3 DE69832178 T3 DE 69832178T3 DE 69832178 T DE69832178 T DE 69832178T DE 69832178 T DE69832178 T DE 69832178T DE 69832178 T3 DE69832178 T3 DE 69832178T3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- 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
- C07K14/70578—NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- 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
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| DE69832178D1 DE69832178D1 (de) | 2005-12-08 |
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| US6313269B1 (en) * | 1997-03-14 | 2001-11-06 | Smithkline Beecham Corporation | Tumor necrosis factor related receptor, TR6 |
| US6872568B1 (en) | 1997-03-17 | 2005-03-29 | Human Genome Sciences, Inc. | Death domain containing receptor 5 antibodies |
| US20080248046A1 (en) * | 1997-03-17 | 2008-10-09 | Human Genome Sciences, Inc. | Death domain containing receptor 5 |
| US20040136951A1 (en) * | 1997-03-17 | 2004-07-15 | Human Genome Sciences, Inc. | Death domain containing receptor 5 |
| US20050233958A1 (en) * | 1997-03-17 | 2005-10-20 | Human Genome Sciences, Inc. | Death domain containing receptor 5 |
| ES2281126T3 (es) * | 1997-03-17 | 2007-09-16 | Human Genome Sciences, Inc. | Receptor 5 que contiene un dominio de muerte. |
| US6342369B1 (en) * | 1997-05-15 | 2002-01-29 | Genentech, Inc. | Apo-2-receptor |
| ATE516354T1 (de) * | 1997-05-15 | 2011-07-15 | Genentech Inc | Apo-2-rezeptor |
| US20100152426A1 (en) * | 1997-05-15 | 2010-06-17 | Ashkenazi Avi J | Apo-2 receptor fusion proteins |
| JP2001514888A (ja) * | 1997-08-15 | 2001-09-18 | アイドゥン ファーマシューティカルズ， インコーポレイテッド | Ｔｒａｉｌレセプター、これをコードする核酸、およびその使用方法 |
| ES2286856T3 (es) * | 1997-09-12 | 2007-12-01 | Biogen Idec Ma Inc. | Receptores train ricos en cisteina. |
| US6252050B1 (en) * | 1998-06-12 | 2001-06-26 | Genentech, Inc. | Method for making monoclonal antibodies and cross-reactive antibodies obtainable by the method |
| IL139419A0 (en) * | 1998-06-12 | 2001-11-25 | Genentech Inc | Monoclonal antibodies, cross-reactive antibodies and method for producing the same |
| US20050281821A1 (en) * | 1999-01-06 | 2005-12-22 | Flavia Pernasetti | Method and composition for angiogenesis inhibition |
| US6627199B1 (en) | 1999-07-09 | 2003-09-30 | Amgen Inc | Isolation, identification and characterization of tmst2, a novel member of the TNF-receptor supergene family |
| US6951738B2 (en) | 1999-07-16 | 2005-10-04 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptors TR13 and TR14 |
| AU780060B2 (en) * | 1999-07-16 | 2005-02-24 | Human Genome Sciences, Inc. | Human tumor necrosis factor receptors TR13 and TR14 |
| CA2381284A1 (en) | 1999-08-04 | 2001-02-15 | Amgen Inc. | Fhm, a novel member of the tnf ligand supergene family |
| WO2001010908A1 (en) | 1999-08-04 | 2001-02-15 | Amgen Inc. | Ntr3, a member of the tnf-receptor supergene family |
| JP2004515203A (ja) * | 1999-08-12 | 2004-05-27 | ヒューマン ジノーム サイエンシーズ， インコーポレイテッド | ヒト腫瘍壊死因子レセプターｔｒ１６ |
| US20030134788A1 (en) * | 1999-08-12 | 2003-07-17 | Baker Kevin P. | Human tumor necrosis factor receptor TR16 |
| WO2001023592A2 (en) * | 1999-09-27 | 2001-04-05 | Genentech, Inc. | Methods for making recombinant proteins using apoptosis inhibitors |
| AU2006201322A1 (en) * | 1999-09-27 | 2006-04-27 | Genentech, Inc. | Methods for making recombinant proteins using apoptosis inhibitors |
| IL150755A0 (en) | 2000-02-16 | 2003-02-12 | Genentech Inc | Uses of agonists and antagonists to modulate activity of tnf-related molecules |
| MXPA02010011A (es) | 2000-04-11 | 2003-04-25 | Genentech Inc | Anticuerpos multivalentes y usos para los mismos. |
| US7279160B2 (en) * | 2000-05-02 | 2007-10-09 | The Uab Research Foundation | Combinations of DR5 antibodies and other therapeutic agents |
| TWI318983B (en) * | 2000-05-02 | 2010-01-01 | Uab Research Foundation | An antibody selective for a tumor necrosis factor-related apoptosis-inducing ligand receptor and uses thereof |
| US7476383B2 (en) * | 2000-05-02 | 2009-01-13 | The Uab Research Foundation | Antibody selective for DR4 and uses thereof |
| KR100436089B1 (ko) * | 2000-07-06 | 2004-06-14 | 설대우 | 분비성 재조합 트라이머형의 트레일 단백질 생산을 위한 디엔에이 카세트, 테트라사이클린/독시사이클린-유도성아데노-관련 바이러스 벡터, 이 둘의 조합, 및 이들을이용한 유전자 치료 |
| US20040005314A1 (en) * | 2001-07-27 | 2004-01-08 | Enrique Escandon | Apo-2l receptor agonist and cpt-11 synergism |
| WO2002009755A2 (en) | 2000-07-27 | 2002-02-07 | Genentech, Inc. | Apo-2l receptor agonist and cpt-11 synergism |
| US20060062786A1 (en) * | 2000-11-08 | 2006-03-23 | Human Genome Sciences, Inc. | Antibodies that immunospecifically bind to TRAIL receptors |
| US20030228309A1 (en) * | 2000-11-08 | 2003-12-11 | Theodora Salcedo | Antibodies that immunospecifically bind to TRAIL receptors |
| CA2426710A1 (en) * | 2000-11-08 | 2002-10-10 | Human Genome Sciences, Inc. | Antibodies that immunospecifically bind to trail receptors |
| US20030139963A1 (en) * | 2000-12-08 | 2003-07-24 | Chickering D. Maxwell | Decision theoretic approach to targeted solicitation by maximizing expected profit increases |
| US20020155109A1 (en) * | 2001-04-20 | 2002-10-24 | Lynch David H. | Bispecific antibodies that bind TRAIL-R1 and TRAIL-R2 |
| US7115717B2 (en) * | 2001-05-18 | 2006-10-03 | Kirin Beer Kabushiki Kaisha | Anti-TRAIL-R antibodies |
| US20090226429A1 (en) * | 2001-05-25 | 2009-09-10 | Human Genome Sciences, Inc. | Antibodies That Immunospecifically Bind to TRAIL Receptors |
| US20050214209A1 (en) * | 2001-05-25 | 2005-09-29 | Human Genome Sciences, Inc. | Antibodies that immunospecifically bind to TRAIL receptors |
| US7361341B2 (en) * | 2001-05-25 | 2008-04-22 | Human Genome Sciences, Inc. | Methods of treating cancer using antibodies that immunospecifically bind to trail receptors |
| ES2437992T3 (es) | 2001-05-25 | 2014-01-15 | Human Genome Sciences, Inc. | Anticuerpos que se unen inmunoespecíficamente a los receptores de TRAIL |
| US20050129616A1 (en) * | 2001-05-25 | 2005-06-16 | Human Genome Sciences, Inc. | Antibodies that immunospecifically bind to TRAIL receptors |
| US7348003B2 (en) | 2001-05-25 | 2008-03-25 | Human Genome Sciences, Inc. | Methods of treating cancer using antibodies that immunospecifically bind to TRAIL receptors |
| CA2451680C (en) | 2001-07-03 | 2011-04-19 | Genentech, Inc. | Human dr4 antibodies and uses thereof |
| US20030082722A1 (en) * | 2001-08-08 | 2003-05-01 | Bingliang Fang | Method for amplifying expression from a cell specific promoter |
| JP2005508162A (ja) | 2001-10-02 | 2005-03-31 | ジェネンテック・インコーポレーテッド | Ａｐｏ−２リガンド変異体とその使用法 |
| IL161812A0 (en) | 2001-11-13 | 2005-11-20 | Genentech Inc | Apo2 ligand/trail formulations |
| US7741285B2 (en) | 2001-11-13 | 2010-06-22 | Genentech, Inc. | APO-2 ligand/trail formulations |
| US7842668B1 (en) | 2001-11-13 | 2010-11-30 | Genentech, Inc. | Apo-2 ligand/trail formulations |
| CA2471140A1 (en) * | 2001-12-20 | 2003-07-03 | Human Genome Sciences, Inc. | Antibodies that immunospecifically bind to trail receptors |
| EP1556076A4 (en) | 2002-06-24 | 2009-07-08 | Genentech Inc | APO-2 LIGAND / TRAIL VARIANTS AND ITS USES |
| PT1606318E (pt) * | 2003-03-26 | 2009-11-10 | Deutsches Krebsforsch | Proteínas de fusão de fc melhoradas |
| WO2005092927A1 (en) | 2004-03-23 | 2005-10-06 | Biogen Idec Ma Inc. | Receptor coupling agents and therapeutic uses thereof |
| AU2005271601A1 (en) | 2004-08-06 | 2006-02-16 | Genentech, Inc. | Assays and methods using biomarkers |
| MX2007001468A (es) * | 2004-08-06 | 2007-03-26 | Genentech Inc | Ensayos y metodos que utilizan biomarcadores. |
| BRPI0515615A (pt) * | 2004-09-08 | 2008-07-29 | Genentech Inc | métodos para tratar células cancerosas e doença imune relacionada |
| EP1802660A2 (en) * | 2004-09-08 | 2007-07-04 | Genentech, Inc. | Methods of using death receptor ligands and cd20 antibodies |
| JO3000B1 (ar) | 2004-10-20 | 2016-09-05 | Genentech Inc | مركبات أجسام مضادة . |
| US8029783B2 (en) | 2005-02-02 | 2011-10-04 | Genentech, Inc. | DR5 antibodies and articles of manufacture containing same |
| BRPI0606791A2 (pt) * | 2005-02-02 | 2010-02-09 | Uab Research Foundation | métodos de reverter ou prevenir a resistência de uma célula a um agonista do receptor da morte, de triar uma célula quanto a um biomarcador da resistência a um agonista do receptor da morte, de monitorar a resistência a um agonista do receptor da morte em um indivìduo, de induzir seletivamente a apoptose em uma célula alvo expressando um receptor da morte, de tratar de um indivìduo com cáncer, de tratar de um indivìduo com uma doença inflamatória ou autoimune, de bloquear a ligação da proteìna contendo card a um receptor da morte em uma célula, de bloquear a associação de um iap com o receptor da morte e de triar um modulador de uma proteìna contendo card, composição, ácido nucleico isolado, vetor, célula, e, polipeptìdeo isolado |
| US20090155247A1 (en) * | 2005-02-18 | 2009-06-18 | Ashkenazi Avi J | Methods of Using Death Receptor Agonists and EGFR Inhibitors |
| US20060188498A1 (en) * | 2005-02-18 | 2006-08-24 | Genentech, Inc. | Methods of using death receptor agonists and EGFR inhibitors |
| US7629315B2 (en) * | 2005-03-09 | 2009-12-08 | University Of Pittsburgh Of The Commonwealth System Of Higher Education | Compositions for blocking the inhibitory effect of human CRP on human leptin |
| PT1915626E (pt) | 2005-08-16 | 2012-02-03 | Genentech Inc | Sensibilidade da apoptose a apo2l/trail por ensaio de expressão de galnac-t14 em células/tecidos |
| CA2619654A1 (en) * | 2005-08-24 | 2007-03-01 | Cell Matrix | Combination therapies for inhibiting integrin-extracellular matrix interactions |
| AU2006318539B2 (en) | 2005-11-23 | 2012-09-13 | Genentech, Inc. | Methods and compositions related to B cell assays |
| US8957187B2 (en) | 2005-12-02 | 2015-02-17 | Genentech, Inc. | Binding polypeptides and uses thereof |
| US20070218504A1 (en) * | 2006-03-09 | 2007-09-20 | University Of Pittsburgh | Human leptin-derived polypeptides and uses thereof |
| JP2012504969A (ja) | 2008-10-10 | 2012-03-01 | アナフォア インコーポレイテッド | Ｔｒａｉｌ−ｒ１及びｔｒａｉｌ−ｒ２に結合するポリペプチド |
| WO2011043835A1 (en) * | 2009-10-09 | 2011-04-14 | Anaphore, Inc. | Polypeptides that bind il-23r |
| KR20120101050A (ko) | 2009-11-05 | 2012-09-12 | 더 유에이비 리서치 파운데이션 | 기저형 유전자형 암의 치료 방법 |
| US8703712B2 (en) | 2010-03-18 | 2014-04-22 | The Uab Research Foundation | Targeting cancer stem cells with DR5 agonists |
| RU2644678C1 (ru) | 2010-10-29 | 2018-02-13 | Дайити Санкио Компани, Лимитед | Новое антитело против dr5 |
| WO2012117336A2 (en) | 2011-02-28 | 2012-09-07 | Istituto Di Ricovero E Cura A Carattere Scientifico Materno-Infantile Burlo Garofolo - Ospedale Di Alta Specializzazione E Di Rilievo Nazionale Per La Salute Della Donna E Del Bambino | Apoptosis-inducing molecules and uses therefor |
| CA2834776A1 (en) | 2011-05-03 | 2012-11-08 | Genentech, Inc. | Therapeutic apo2l/trail polypeptides and death receptor agonist antibodies |
| CN102898526A (zh) * | 2011-07-28 | 2013-01-30 | 山东先声麦得津生物制药有限公司 | 一种肿瘤坏死因子相关凋亡诱导配体融合蛋白及其制备和应用 |
| WO2014159562A1 (en) | 2013-03-14 | 2014-10-02 | Bristol-Myers Squibb Company | Combination of dr5 agonist and anti-pd-1 antagonist and methods of use |
| GB201312155D0 (en) * | 2013-07-05 | 2013-08-21 | Ucl Business Plc | Therapeutic invention |
| WO2015138638A1 (en) | 2014-03-11 | 2015-09-17 | Theraly Pharmaceuticals, Inc. | Long acting trail receptor agonists for treatment of autoimmune diseases |
| US11007251B2 (en) | 2015-12-17 | 2021-05-18 | The Johns Hopkins University | Ameliorating systemic sclerosis with death receptor agonists |
| CN109195620B (zh) | 2016-04-07 | 2022-06-28 | 约翰霍普金斯大学 | 用死亡受体激动剂治疗胰腺炎和疼痛的组合物和方法 |
| EP3323428A1 (en) | 2016-11-17 | 2018-05-23 | CNRS Centre National de la Recherche Scientifique | Selective c-flip inhibitors as anticancer agents |
| EP3910331A1 (en) | 2020-05-15 | 2021-11-17 | iOmx Therapeutics AG | Intracellular kinase associated with resistance against t-cell mediated cytotoxicity, and uses thereof |
| GB202016058D0 (en) | 2020-10-09 | 2020-11-25 | Ucl Business Ltd | Therapeautic treatment |
| EP4257132A1 (en) | 2022-04-08 | 2023-10-11 | iOmx Therapeutics AG | Sik3 inhibitors for treating diseases resistant to death receptor signalling |
| WO2024175554A1 (en) | 2023-02-21 | 2024-08-29 | Institut Curie | Trail agonists for use in the treatment of cancer in patients having an activating alteration of fgfr3 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100510234B1 (ko) | 1995-06-29 | 2005-11-25 | 임뮤넥스 코포레이션 | 세포소멸을 유도하는 시토킨 |
| ES2284199T5 (es) | 1997-01-28 | 2011-11-14 | Human Genome Sciences, Inc. | Receptor 4 que contiene dominio de muerte (dr4: receptor 4 de muerte), miembro de la superfamilia de receptores de tnf y unión a trail (apo-2l). |
| US20010010924A1 (en) * | 1997-03-14 | 2001-08-02 | Keith Charles Deen | Tumor necrosis factor related receptor, tr6 polynecleotides |
| US6313269B1 (en) * | 1997-03-14 | 2001-11-06 | Smithkline Beecham Corporation | Tumor necrosis factor related receptor, TR6 |
| ES2281126T3 (es) * | 1997-03-17 | 2007-09-16 | Human Genome Sciences, Inc. | Receptor 5 que contiene un dominio de muerte. |
| US6872568B1 (en) * | 1997-03-17 | 2005-03-29 | Human Genome Sciences, Inc. | Death domain containing receptor 5 antibodies |
| EP1007562A4 (en) * | 1997-04-16 | 2000-09-27 | Millennium Pharm Inc | TANGO-63d AND TANGO-63e PROTEINS RELATED TO THE TUMOR NECROSIS FACTOR RECEPTOR |
| ATE516354T1 (de) * | 1997-05-15 | 2011-07-15 | Genentech Inc | Apo-2-rezeptor |
| US6342369B1 (en) * | 1997-05-15 | 2002-01-29 | Genentech, Inc. | Apo-2-receptor |
| AU8400398A (en) | 1997-07-11 | 1999-02-08 | Trustees Of The University Of Pennsylvania, The | Nucleic acid encoding a novel chemotherapy-induced protein, and methods of use |
| JP2001514888A (ja) | 1997-08-15 | 2001-09-18 | アイドゥン ファーマシューティカルズ， インコーポレイテッド | Ｔｒａｉｌレセプター、これをコードする核酸、およびその使用方法 |
| ES2286856T3 (es) | 1997-09-12 | 2007-12-01 | Biogen Idec Ma Inc. | Receptores train ricos en cisteina. |
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| IL131030A0 (en) | 2001-01-28 |
| EP1005488A4 (en) | 2003-03-05 |
| US6072047A (en) | 2000-06-06 |
| WO1998035986A1 (en) | 1998-08-20 |
| ATE308561T1 (de) | 2005-11-15 |
| EP1005488B2 (en) | 2011-12-14 |
| ES2251767T3 (es) | 2006-05-01 |
| US6569642B1 (en) | 2003-05-27 |
| EP1005488B1 (en) | 2005-11-02 |
| IL131030A (en) | 2011-02-28 |
| DE69832178T2 (de) | 2006-07-20 |
| EP1676857A2 (en) | 2006-07-05 |
| NZ336929A (en) | 2000-11-24 |
| ES2251767T9 (es) | 2012-10-17 |
| DE69832178D1 (de) | 2005-12-08 |
| ES2251767T5 (es) | 2012-03-07 |
| EP1005488A1 (en) | 2000-06-07 |
| HK1029796A1 (en) | 2001-04-12 |
| EP1676857A3 (en) | 2007-04-04 |
| EP1005488B9 (en) | 2012-04-18 |
| JP5031132B2 (ja) | 2012-09-19 |
| DK1005488T3 (da) | 2006-03-06 |
| JP2002514069A (ja) | 2002-05-14 |
| AU735686B2 (en) | 2001-07-12 |
| CA2279838A1 (en) | 1998-08-20 |
| US6642358B1 (en) | 2003-11-04 |
| DK1005488T4 (da) | 2012-01-16 |
| AU6650598A (en) | 1998-09-08 |
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