RU2298013C2 - Антитело, обладающее селективностью по отношению к рецептору лиганда, индуцирующему апоптоз, ассоциированный с фактором некроза опухоли, и его использование - Google Patents
Антитело, обладающее селективностью по отношению к рецептору лиганда, индуцирующему апоптоз, ассоциированный с фактором некроза опухоли, и его использование Download PDFInfo
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Families Citing this family (83)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7528239B1 (en) | 1997-02-13 | 2009-05-05 | Immunex Corporation | Receptor that binds trail |
| US6872568B1 (en) | 1997-03-17 | 2005-03-29 | Human Genome Sciences, Inc. | Death domain containing receptor 5 antibodies |
| AU747635B2 (en) | 1997-03-17 | 2002-05-16 | Human Genome Sciences, Inc. | Death domain containing receptor 5 |
| JP2002543151A (ja) * | 1999-05-04 | 2002-12-17 | 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 | 死ドメイン含有レセプター５ |
| 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 |
| US7279160B2 (en) | 2000-05-02 | 2007-10-09 | The Uab Research Foundation | Combinations of DR5 antibodies and other therapeutic agents |
| US20030228309A1 (en) * | 2000-11-08 | 2003-12-11 | Theodora Salcedo | Antibodies that immunospecifically bind to TRAIL receptors |
| US20060062786A1 (en) * | 2000-11-08 | 2006-03-23 | Human Genome Sciences, Inc. | Antibodies that immunospecifically bind to TRAIL receptors |
| AU2003222427B8 (en) | 2000-11-17 | 2010-04-29 | Vascular Biogenics Ltd. | Promoters exhibiting endothelial cell specificity and methods of using same |
| US8071740B2 (en) * | 2000-11-17 | 2011-12-06 | Vascular Biogenics Ltd. | Promoters exhibiting endothelial cell specificity and methods of using same for regulation of angiogenesis |
| CN100475848C (zh) | 2001-05-18 | 2009-04-08 | 麒麟麦酒株式会社 | 抗trail-r抗体 |
| US20050214209A1 (en) * | 2001-05-25 | 2005-09-29 | Human Genome Sciences, Inc. | 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 |
| US7361341B2 (en) | 2001-05-25 | 2008-04-22 | Human Genome Sciences, Inc. | Methods of treating cancer using antibodies that immunospecifically bind to trail receptors |
| 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 |
| US20090226429A1 (en) * | 2001-05-25 | 2009-09-10 | Human Genome Sciences, Inc. | Antibodies That Immunospecifically Bind to TRAIL Receptors |
| EP2277887A3 (en) | 2001-10-19 | 2011-02-16 | Vascular Biogenics Ltd. | Polynucleotide constructs, pharmaceutical compositions and methods for targeted downregulation of angiogenesis and anticancer therapy |
| ES2357225T3 (es) * | 2001-11-01 | 2011-04-20 | Uab Research Foundation | Combinaciones de anticuerpos anti-dr5 y anticuerpos anti-dr4 y otros agentes terapéuticos. |
| AU2002360307B2 (en) * | 2001-11-01 | 2008-01-17 | The Uab Research Foundation | Combinations of DR5 antibody and other therapeutic agents |
| KR20040070254A (ko) * | 2001-12-20 | 2004-08-06 | 휴먼 게놈 사이언시즈, 인코포레이티드 | Ｔｒａｉｌ 수용체에 면역특이적으로 결합하는 항체 |
| US20050069549A1 (en) | 2002-01-14 | 2005-03-31 | William Herman | Targeted ligands |
| DE10210427A1 (de) * | 2002-03-09 | 2003-10-09 | Hans Konrad Mueller-Hermelink | Humaner monoklonaler Antikörper |
| CA2491669A1 (en) | 2002-07-04 | 2004-01-15 | Oncomab Gmbh | Neoplasm specific antibodies and uses thereof |
| AU2008201431B2 (en) * | 2002-11-27 | 2011-11-24 | Irm, Llc | Methods and compositions for inducing Apoptosis in cancer cells |
| WO2004050895A2 (en) * | 2002-11-27 | 2004-06-17 | Irm Llc | Methods and compositions for inducing apoptosis in cancer cells |
| DE10311248A1 (de) | 2003-03-14 | 2004-09-30 | Müller-Hermelink, Hans Konrad, Prof. Dr. | Humaner monoklonaler Antikörper |
| DE10353175A1 (de) | 2003-11-14 | 2005-06-16 | Müller-Hermelink, Hans Konrad, Prof. Dr. | Humaner monoklonaler Antikörper mit fettsenkender Wirkung |
| EP1531162A1 (en) | 2003-11-14 | 2005-05-18 | Heinz Vollmers | Adenocarcinoma specific antibody SAM-6, and uses thereof |
| EP1756162A1 (en) | 2004-03-23 | 2007-02-28 | Biogen Idec MA Inc. | Receptor coupling agents and therapeutic uses thereof |
| CN100427505C (zh) * | 2004-08-19 | 2008-10-22 | 中国医学科学院基础医学研究所 | 抗人肿瘤坏死因子相关凋亡诱导配体的受体dr5单克隆抗体（ad5-10）及其制法与用途 |
| NZ554390A (en) * | 2004-12-13 | 2010-07-30 | Cephalon Australia Vic Pty Ltd | Osteoprotegerin variant proteins |
| CN101495646A (zh) | 2005-02-02 | 2009-07-29 | Uab研究基金会 | 与降低对细胞凋亡诱导性死亡受体激动剂的抗性有关的试剂和方法 |
| US8029783B2 (en) | 2005-02-02 | 2011-10-04 | Genentech, Inc. | DR5 antibodies and articles of manufacture containing same |
| JP5004154B2 (ja) * | 2005-04-06 | 2012-08-22 | 一般財団法人化学及血清療法研究所 | 組換え抗ボツリヌス神経毒素抗体 |
| JP5372500B2 (ja) | 2005-06-17 | 2013-12-18 | トレラクス リクイデーティング トラスト | Ｉｌｔ３結合分子およびその使用 |
| CN101300273B (zh) * | 2005-08-31 | 2013-05-22 | 安姆根有限公司 | Trail受体2多肽和抗体 |
| PE20071101A1 (es) * | 2005-08-31 | 2007-12-21 | Amgen Inc | Polipeptidos y anticuerpos |
| US8168181B2 (en) | 2006-02-13 | 2012-05-01 | Alethia Biotherapeutics, Inc. | Methods of impairing osteoclast differentiation using antibodies that bind siglec-15 |
| KR20090031359A (ko) | 2006-05-16 | 2009-03-25 | 교와 핫꼬 기린 가부시키가이샤 | 단백질의 고분비 생산 방법 |
| EP2041180B8 (en) * | 2006-06-19 | 2014-03-05 | Liquidating Trust | Ilt3 binding molecules and uses therefor |
| KR100847010B1 (ko) * | 2006-07-05 | 2008-07-17 | 아주대학교산학협력단 | 세포사멸 수용체 5 (ｄｒ5)에 특이적으로 결합하는 항체 및이를 포함하는 암 예방 또는 치료용 조성물 |
| KR100804126B1 (ko) | 2007-02-09 | 2008-02-19 | 아주대학교산학협력단 | 종양 괴사 인자―관련 세포사멸―유도 리간드의 수용체에특이적으로 결합하는 1가의 인간 단일클론 항체 및 그의항원결합 단편 |
| PE20090765A1 (es) * | 2007-06-08 | 2009-07-10 | Irm Llc | Metodos y composiciones para inducir la apoptosis en celulas cancerosas |
| JPWO2009020093A1 (ja) * | 2007-08-09 | 2010-11-04 | 第一三共株式会社 | デスドメイン含有受容体発現細胞にアポトーシスを誘導するイムノリポソーム |
| US8409825B2 (en) | 2007-10-31 | 2013-04-02 | National Institute Of Advanced Industrial Science And Technology | Method for high-level secretory production of protein |
| WO2010047509A2 (ko) * | 2008-10-24 | 2010-04-29 | 아주대학교 산학협력단 | 친화도와 안정성이 향상된 항 ｄｒ5 항체, 및 이를 포함하는 암 예방 또는 치료용 조성물 |
| WO2011038159A2 (en) * | 2009-09-24 | 2011-03-31 | Seattle Genetics, Inc. | Dr5 ligand drug conjugates |
| US9068019B2 (en) | 2009-10-19 | 2015-06-30 | Hanall Biopharma Co., Ltd. | Modified human tumor necrosis factor receptor-1 polypeptide or fragment thereof, and method for preparing same |
| BR112012010698A2 (pt) | 2009-11-05 | 2016-11-29 | Uab Research Foundation | método para tratamento de um sujeito com câncer, método de triagem de uma célula de câncer de mama, e , anticorpo |
| WO2011084623A1 (en) | 2009-12-16 | 2011-07-14 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Method of sensitizing cancer cells to the cytotoxic effects of death receptor ligands in cancer treatment |
| US9120855B2 (en) | 2010-02-10 | 2015-09-01 | Novartis Ag | Biologic compounds directed against death receptor 5 |
| CN102985439B9 (zh) | 2010-02-12 | 2016-08-03 | 制药科学股份有限公司 | Iap bir结构域结合化合物 |
| US8703712B2 (en) | 2010-03-18 | 2014-04-22 | The Uab Research Foundation | Targeting cancer stem cells with DR5 agonists |
| MX344200B (es) * | 2010-10-29 | 2016-12-08 | Daiichi Sankyo Co Ltd | Novedoso anticuerpo anti-dr5. |
| EP3138581B1 (en) | 2011-03-17 | 2019-01-02 | The University of Birmingham | Re-directed immunotherapy |
| CA2834776A1 (en) * | 2011-05-03 | 2012-11-08 | Genentech, Inc. | Therapeutic apo2l/trail polypeptides and death receptor agonist antibodies |
| CN104507969A (zh) | 2012-07-19 | 2015-04-08 | 阿莱斯亚生物疗法股份有限公司 | 抗siglec-15抗体 |
| CN103074425B (zh) * | 2012-12-29 | 2014-01-01 | 深圳市第三人民医院 | Cd263基因的用途 |
| US10035847B2 (en) | 2013-10-02 | 2018-07-31 | The Rockefeller University | Amyloid protofibril antibodies and methods of use thereof |
| CN104710533A (zh) * | 2013-12-12 | 2015-06-17 | 中国科学院深圳先进技术研究院 | sDR5-Fc融合蛋白及其用途 |
| CA2972990A1 (en) | 2015-01-20 | 2016-07-28 | Beatrice Tien-Yi WANG | Tumor necrosis factor (tnf) superfamily receptor binding molecules and uses thereof |
| US10501552B2 (en) | 2015-01-26 | 2019-12-10 | Macrogenics, Inc. | Multivalent molecules comprising DR5-binding domains |
| CN105061604B (zh) * | 2015-08-19 | 2018-03-16 | 河南大学 | sDR5‑Fc融合蛋白突变体及其应用 |
| MX391162B (es) | 2015-10-30 | 2025-03-21 | Galaxy Biotech Llc | Anticuerpos altamente potentes que se unen a receptor de muerte 4 y receptor de muerte 5 |
| BR112018011100A2 (en) | 2015-12-01 | 2018-12-04 | Genmab B.V. | antibody, composition, nucleic acid construct, expression vector, host cell, method for treating an individual having a cancer, kit of parts, and use of an antibody or composition. |
| CN106924735A (zh) * | 2015-12-29 | 2017-07-07 | 上海交通大学医学院附属瑞金医院 | 多巴胺1类受体激动剂在制备肿瘤治疗药物中的用途 |
| WO2017139485A1 (en) | 2016-02-09 | 2017-08-17 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Method of sensitizing cancer cells to the cytotoxic effects of apoptosis inducing ligands in cancer treatment |
| EP3423495B1 (en) | 2016-03-01 | 2021-10-20 | Yissum Research Development Company of The Hebrew University of Jerusalem Ltd. | Antibodies specific to human poliovirus receptor (pvr) |
| KR101926166B1 (ko) * | 2016-05-24 | 2018-12-06 | 재단법인 아산사회복지재단 | 수용체 시너지 활성을 이용한 nk 세포의 활성도 검사 방법 및 이를 이용한 nk 세포의 활성도가 관련된 질환의 진단 방법 |
| EP3574017A1 (en) | 2017-01-27 | 2019-12-04 | Kymab Limited | Anti-opg antibodies |
| KR101926834B1 (ko) | 2017-03-21 | 2018-12-07 | 동아에스티 주식회사 | 항-dr5 항체 및 그의 용도 |
| MX2019014407A (es) | 2017-06-07 | 2020-02-05 | Genmab Bv | Anticuerpos terapeuticos basados en hexameros de inmunoglobulina g (igg) mutados. |
| KR101951025B1 (ko) | 2017-08-17 | 2019-02-21 | 서울대학교산학협력단 | 세포사멸 수용체 저해제를 유효성분으로 포함하는 cx3cl1 케모카인 과발현으로 인한 질환 예방 또는 치료용 조성물 |
| AU2018338205A1 (en) * | 2017-09-22 | 2020-05-07 | Immunogen, Inc. | Separation of triple-light chain antibodies using cation exchange chromatography |
| WO2019100193A1 (zh) * | 2017-11-21 | 2019-05-31 | 深圳先进技术研究院 | 抗dr5的抗体及其制备方法和应用 |
| WO2019100194A1 (zh) * | 2017-11-21 | 2019-05-31 | 深圳先进技术研究院 | 抗dr5的抗体及其制备方法和应用 |
| CN108251443A (zh) * | 2018-01-23 | 2018-07-06 | 深圳市人民医院 | 一种tnfrsf10c重组质粒、制备方法及其应用 |
| WO2019173499A1 (en) | 2018-03-06 | 2019-09-12 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | 17-beta-hydroxywithanolides and use thereof in treating cancer |
| CN110305211A (zh) | 2018-03-20 | 2019-10-08 | 鸿运华宁（杭州）生物医药有限公司 | Gipr抗体及其与glp-1的融合蛋白质，以及其药物组合物和应用 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2073722C1 (ru) * | 1990-12-28 | 1997-02-20 | Фармиталиа Карло Эрба С.Р.Л. | Моноклональное антитело, продуцируемое штаммом гибридных культивируемых клеток мыши mus musculus l. есасс n 90110707, f(ab)-фрагмент моноклонального антитела, продуцируемого штаммом гибридных культивируемых клеток мыши mus musculus l. есасс n 90110707, f(ab)*002-фрагмент моноклонального антитела, продуцируемого штаммом гибридных культивируемых клеток мыши mus musculus l. есасс n 90110707, штамм гибридных культивируемых клеток мыши mus musculus l., продуцирующий моноклональное антитело и способ получения штамма гибридных культивируемых клеток мыши mus musculus l. есасс n 90110707 |
Family Cites Families (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) * | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
| US6812327B1 (en) | 1996-10-25 | 2004-11-02 | Human Genome Sciences, Inc. | Neutrokine-alpha polypeptides |
| WO1998032856A1 (en) | 1997-01-28 | 1998-07-30 | Human Genome Sciences, Inc. | Death domain containing receptor 4 (dr4: death receptor 4), member of the tnf-receptor superfamily and binding to trail (ap02-l) |
| US6433147B1 (en) | 1997-01-28 | 2002-08-13 | Human Genome Sciences, Inc. | Death domain containing receptor-4 |
| US6072047A (en) * | 1997-02-13 | 2000-06-06 | Immunex Corporation | Receptor that binds trail |
| US6313269B1 (en) | 1997-03-14 | 2001-11-06 | Smithkline Beecham Corporation | Tumor necrosis factor related receptor, TR6 |
| AU747635B2 (en) | 1997-03-17 | 2002-05-16 | Human Genome Sciences, Inc. | Death domain containing receptor 5 |
| US6872568B1 (en) * | 1997-03-17 | 2005-03-29 | Human Genome Sciences, Inc. | Death domain containing receptor 5 antibodies |
| AU734758B2 (en) | 1997-04-01 | 2001-06-21 | Sankyo Company Limited | Anti-fas antibodies |
| AU7126498A (en) | 1997-04-16 | 1998-11-11 | Millennium Pharmaceuticals, Inc. | Tumor necrosis factor receptor related proteins tango-63d and tango-63e |
| ES2293682T5 (es) | 1997-05-15 | 2011-11-17 | Genentech, Inc. | Anticuerpo anti-apo2. |
| US6342369B1 (en) * | 1997-05-15 | 2002-01-29 | Genentech, Inc. | Apo-2-receptor |
| WO1999002653A1 (en) | 1997-07-11 | 1999-01-21 | Trustees Of The University Of Pennsylvania | Nucleic acid encoding a novel chemotherapy-induced protein, and methods of use |
| AU8395798A (en) * | 1997-07-15 | 1999-02-10 | Immunex Corporation | Trail receptor |
| AU3710597A (en) | 1997-08-06 | 1999-03-01 | Laboratorio Medinfar-Produtos Farmaceuticos, Lda | Dna integration into "mycobacterium spp." genome by trans-complementation using a site-specific integration system |
| ATE233887T1 (de) * | 1997-08-13 | 2003-03-15 | Sortech Ag | Sorptionsspeicher, anordnung und verfahren zur speicherung von wärme |
| US6417328B2 (en) * | 1997-08-15 | 2002-07-09 | Thomas Jefferson Univeristy | Trail receptors, nucleic acids encoding the same, and methods of use thereof |
| AU9376498A (en) | 1997-09-05 | 1999-03-22 | University Of Washington | Tumor necrosis factor family receptors and ligands, encoding nucleic acids and related binding agents |
| ES2286856T3 (es) | 1997-09-12 | 2007-12-01 | Biogen Idec Ma Inc. | Receptores train ricos en cisteina. |
| US7105640B2 (en) * | 1997-10-17 | 2006-09-12 | Genentech, Inc. | Anti-pro792 antibodies |
| PT1053256E (pt) | 1998-01-26 | 2011-09-28 | Genentech Inc | Anticorpos para o receptor de morte 4 (dr4) e utilizações destes |
| US20040120947A1 (en) | 1998-01-26 | 2004-06-24 | Genentech, Inc. | DR4 antibodies and uses thereof |
| US6252050B1 (en) | 1998-06-12 | 2001-06-26 | Genentech, Inc. | Method for making monoclonal antibodies and cross-reactive antibodies obtainable by the method |
| WO2000061757A1 (en) | 1999-04-12 | 2000-10-19 | Genentech, Inc. | Tumor necrosis factor homologs and nucleic acids encoding the same |
| JP2002543151A (ja) | 1999-05-04 | 2002-12-17 | 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 | 死ドメイン含有レセプター５ |
| WO2000067793A1 (en) | 1999-05-06 | 2000-11-16 | Human Genome Sciences, Inc. | Death domain containing receptor 4 |
| IL146448A0 (en) | 1999-05-28 | 2002-07-25 | Genentech Inc | Dr4 antibodies and uses thereof |
| ES2267547T3 (es) | 1999-06-09 | 2007-03-16 | Genentech, Inc. | Sinergia de antagonista de receptores del ligando apo-2l y de cpt-11. |
| US6294546B1 (en) | 1999-08-30 | 2001-09-25 | The Broad Of Trustees Of The Leland Stanford Junior University | Uses of diterpenoid triepoxides as an anti-proliferative agent |
| JP2003510253A (ja) | 1999-09-15 | 2003-03-18 | ジェネンテック・インコーポレーテッド | Ａｐｏ−２レセプター抗体 |
| MXPA02010011A (es) | 2000-04-11 | 2003-04-25 | Genentech Inc | Anticuerpos multivalentes y usos para los mismos. |
| US7476383B2 (en) * | 2000-05-02 | 2009-01-13 | The Uab Research Foundation | Antibody selective for DR4 and uses thereof |
| 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 |
| US7279160B2 (en) | 2000-05-02 | 2007-10-09 | The Uab Research Foundation | Combinations of DR5 antibodies and other therapeutic agents |
| CA2426710A1 (en) | 2000-11-08 | 2002-10-10 | 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 |
| US6965023B2 (en) * | 2000-11-17 | 2005-11-15 | The Burnham Institute | Death domain proteins |
| AU2002366430B2 (en) | 2001-07-03 | 2008-09-18 | Genentech, Inc. | Human DR4 antibodies and uses thereof |
| AU2002360307B2 (en) | 2001-11-01 | 2008-01-17 | The Uab Research Foundation | Combinations of DR5 antibody and other therapeutic agents |
| ES2357225T3 (es) | 2001-11-01 | 2011-04-20 | Uab Research Foundation | Combinaciones de anticuerpos anti-dr5 y anticuerpos anti-dr4 y otros agentes terapéuticos. |
-
2001
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- 2001-05-02 AU AU5936601A patent/AU5936601A/xx active Pending
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2073722C1 (ru) * | 1990-12-28 | 1997-02-20 | Фармиталиа Карло Эрба С.Р.Л. | Моноклональное антитело, продуцируемое штаммом гибридных культивируемых клеток мыши mus musculus l. есасс n 90110707, f(ab)-фрагмент моноклонального антитела, продуцируемого штаммом гибридных культивируемых клеток мыши mus musculus l. есасс n 90110707, f(ab)*002-фрагмент моноклонального антитела, продуцируемого штаммом гибридных культивируемых клеток мыши mus musculus l. есасс n 90110707, штамм гибридных культивируемых клеток мыши mus musculus l., продуцирующий моноклональное антитело и способ получения штамма гибридных культивируемых клеток мыши mus musculus l. есасс n 90110707 |
Non-Patent Citations (1)
| Title |
|---|
| GRIFFITH T.S. et al., Functional analysis of TRAIL receptors using monoclonal antibodies, 1999, J. Immunol., v.162, n.5, p.2597-2605. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2681730C2 (ru) * | 2012-07-25 | 2019-03-12 | Селлдекс Терапьютикс Инк. | Антитела против kit и их применения |
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