JP2013505732A5 - - Google Patents
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- JP2013505732A5 JP2013505732A5 JP2012531338A JP2012531338A JP2013505732A5 JP 2013505732 A5 JP2013505732 A5 JP 2013505732A5 JP 2012531338 A JP2012531338 A JP 2012531338A JP 2012531338 A JP2012531338 A JP 2012531338A JP 2013505732 A5 JP2013505732 A5 JP 2013505732A5
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| BR112016006929A2 (pt) | 2013-10-11 | 2017-09-19 | Hoffmann La Roche | Anticorpo, ácido nucleico, vetor de expressão, célula hospedeira, métodos de preparação de anticorpo, de tratamento de pacientes e de geração de um anticorpo, composição farmacêutica e uso do anticorpo |
| ES2900898T3 (es) | 2014-04-07 | 2022-03-18 | Chugai Pharmaceutical Co Ltd | Anticuerpos biespecíficos inmunoactivadores |
| CA2947157A1 (en) | 2014-05-13 | 2015-11-19 | Chugai Seiyaku Kabushiki Kaisha | T cell-redirected antigen-binding molecule for cells having immunosuppression function |
| KR20170063946A (ko) * | 2014-10-08 | 2017-06-08 | 에프. 호프만-라 로슈 아게 | Fap 및 dr5에 특이적인 이중특이성 항체와 화학요법제의 병용요법 |
| WO2016077638A1 (en) * | 2014-11-12 | 2016-05-19 | Memorial Sloan Kettering Cancer Center | Anti-chondroitin sulfate proteoglycan 4 antibodies and uses thereof |
| DK3489256T3 (da) | 2014-11-14 | 2021-05-25 | Hoffmann La Roche | Antigenbindende molekyler omfattende en TNF-familieligandtrimer |
| US11566082B2 (en) | 2014-11-17 | 2023-01-31 | Cytiva Bioprocess R&D Ab | Mutated immunoglobulin-binding polypeptides |
| WO2016087416A1 (en) | 2014-12-03 | 2016-06-09 | F. Hoffmann-La Roche Ag | Multispecific antibodies |
| WO2016103205A1 (en) * | 2014-12-23 | 2016-06-30 | Universita' Degli Studi Di Parma | Pro-apoptotic anti-ng2/cspg4 antibodies and their uses for disease therapy |
| AU2015380455A1 (en) | 2015-01-26 | 2017-08-03 | Macrogenics, Inc. | Multivalent molecules comprising DR5-binding domains |
| CN104818295A (zh) * | 2015-02-03 | 2015-08-05 | 武汉友芝友生物制药有限公司 | 制备和筛选表达双特异性抗体细胞株的方法 |
| EP3973980A1 (en) | 2015-03-31 | 2022-03-30 | F. Hoffmann-La Roche AG | Antigen binding molecules comprising a trimeric tnf family ligand |
| AR106188A1 (es) | 2015-10-01 | 2017-12-20 | Hoffmann La Roche | Anticuerpos anti-cd19 humano humanizados y métodos de utilización |
| MA43017A (fr) | 2015-10-02 | 2018-08-08 | Hoffmann La Roche | Anticorps bispécifiques spécifiques d'un récepteur de co-stimulation du tnf |
| WO2017055395A1 (en) * | 2015-10-02 | 2017-04-06 | F. Hoffmann-La Roche Ag | Anti-cd3xrob04 bispecific t cell activating antigen binding molecules |
| WO2017086367A1 (ja) | 2015-11-18 | 2017-05-26 | 中外製薬株式会社 | 免疫抑制機能を有する細胞に対するｔ細胞リダイレクト抗原結合分子を用いた併用療法 |
| JP6925278B2 (ja) | 2015-11-18 | 2021-08-25 | 中外製薬株式会社 | 液性免疫応答の増強方法 |
| CN109311949B (zh) | 2016-05-11 | 2022-09-16 | 思拓凡生物工艺研发有限公司 | 储存分离基质的方法 |
| US10654887B2 (en) | 2016-05-11 | 2020-05-19 | Ge Healthcare Bio-Process R&D Ab | Separation matrix |
| US10730908B2 (en) | 2016-05-11 | 2020-08-04 | Ge Healthcare Bioprocess R&D Ab | Separation method |
| WO2017194593A1 (en) | 2016-05-11 | 2017-11-16 | Ge Healthcare Bioprocess R&D Ab | Method of cleaning and/or sanitizing a separation matrix |
| US10703774B2 (en) | 2016-09-30 | 2020-07-07 | Ge Healthcare Bioprocess R&D Ab | Separation method |
| JP7031934B2 (ja) | 2016-05-11 | 2022-03-08 | サイティバ・バイオプロセス・アールアンドディ・アクチボラグ | 分離マトリックス |
| US10889615B2 (en) | 2016-05-11 | 2021-01-12 | Cytiva Bioprocess R&D Ab | Mutated immunoglobulin-binding polypeptides |
| US10513537B2 (en) | 2016-05-11 | 2019-12-24 | Ge Healthcare Bioprocess R&D Ab | Separation matrix |
| US12448411B2 (en) | 2016-09-30 | 2025-10-21 | Cytiva Bioprocess R&D Ab | Separation method |
| EP3360898A1 (en) * | 2017-02-14 | 2018-08-15 | Boehringer Ingelheim International GmbH | Bispecific anti-tnf-related apoptosis-inducing ligand receptor 2 and anti-cadherin 17 binding molecules for the treatment of cancer |
| US11613785B2 (en) | 2017-01-09 | 2023-03-28 | Onkosxcel Therapeutics, Llc | Predictive and diagnostic methods for prostate cancer |
| EP3710482A4 (en) * | 2017-11-14 | 2021-08-18 | University Of Virginia Patent Foundation | COMPOSITIONS AND METHODS OF MANUFACTURING AND USING BISPECIFIC ANTIBODIES |
| KR20210009421A (ko) | 2018-06-14 | 2021-01-26 | 바이오아트라, 엘엘씨 | 다중 특이적 항체 구조체 |
| US12194000B2 (en) * | 2018-08-01 | 2025-01-14 | The Wistar Institute Of Anatomy And Biology | Optimized synthetic consensus immunogenic compositions targeting chondroitin sulfate proteoglycan 4 (CSPG4) |
| CR20240246A (es) * | 2021-12-20 | 2024-07-19 | Hoffmann La Roche | Anticuerpos agonistas anti-ltbr y anticuerpos biespecificos que los comprenden |
| EP4554677A1 (en) | 2022-07-15 | 2025-05-21 | Boehringer Ingelheim International GmbH | Binding molecules for the treatment of cancer |
| AU2023375570A1 (en) | 2022-11-10 | 2025-06-12 | Immuvia Inc | Cytotoxic bispecific antibodies binding to dr5 and muc16 and uses thereof |
| US12351650B2 (en) | 2023-06-30 | 2025-07-08 | Genmab A/S | Antibodies binding to fibroblast activation protein alpha and death receptor 4 |
| WO2025098480A1 (zh) * | 2023-11-10 | 2025-05-15 | 信达生物制药(苏州)有限公司 | 抗dr5和ceacam5的双特异性抗体及其用途 |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU600575B2 (en) | 1987-03-18 | 1990-08-16 | Sb2, Inc. | Altered antibodies |
| US5202238A (en) | 1987-10-27 | 1993-04-13 | Oncogen | Production of chimeric antibodies by homologous recombination |
| US5204244A (en) | 1987-10-27 | 1993-04-20 | Oncogen | Production of chimeric antibodies by homologous recombination |
| US5580774A (en) | 1989-07-31 | 1996-12-03 | Eli Lilly And Company | Chimeric antibodies directed against a human glycoprotein antigen |
| GB9317423D0 (en) * | 1993-08-21 | 1993-10-06 | Imp Cancer Res Tech | Monoclonal antibodies |
| DE10034607A1 (de) * | 2000-07-20 | 2002-02-07 | Gundram Jung | Multispezifisches Reagenz zur selektiven Stimulierung von Zelloberflächenrezeptoren |
| DE10045591A1 (de) * | 2000-09-15 | 2002-04-04 | Klaus Pfizenmaier | Ortsspezifische, antikörpervermittelte Aktivierung proapoptotischer Zytokine - AMAIZe (Antibody-Mediated Apoptosis Inducing Zytokine) |
| US20020155109A1 (en) * | 2001-04-20 | 2002-10-24 | Lynch David H. | Bispecific antibodies that bind TRAIL-R1 and TRAIL-R2 |
| US7232888B2 (en) | 2002-07-01 | 2007-06-19 | Massachusetts Institute Of Technology | Antibodies against tumor surface antigens |
| SG151294A1 (en) * | 2004-03-23 | 2009-04-30 | Biogen Idec Inc | Receptor coupling agents and therapeutic uses thereof |
| US7632497B2 (en) * | 2004-11-10 | 2009-12-15 | Macrogenics, Inc. | Engineering Fc Antibody regions to confer effector function |
| EP2311880A3 (en) * | 2005-01-05 | 2011-07-27 | Biogen Idec MA Inc. | Cripto binding molecules |
| US8029783B2 (en) * | 2005-02-02 | 2011-10-04 | Genentech, Inc. | DR5 antibodies and articles of manufacture containing same |
| TWI671403B (zh) | 2005-03-31 | 2019-09-11 | 中外製藥股份有限公司 | 控制組裝之多肽的製造方法 |
| SG187746A1 (en) | 2010-08-13 | 2013-03-28 | Roche Glycart Ag | Anti-fap antibodies and methods of use |
| UA118028C2 (uk) | 2013-04-03 | 2018-11-12 | Рош Глікарт Аг | Біспецифічне антитіло, специфічне щодо fap і dr5, антитіло, специфічне щодо dr5, і спосіб їх застосування |
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2010
- 2010-09-27 CA CA 2773515 patent/CA2773515C/en not_active Expired - Fee Related
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- 2010-09-27 MX MX2012003598A patent/MX2012003598A/es active IP Right Grant
- 2010-09-27 EP EP10757604.3A patent/EP2483310B1/en active Active
- 2010-09-27 US US13/498,390 patent/US9481730B2/en not_active Expired - Fee Related
- 2010-09-27 AU AU2010303142A patent/AU2010303142B2/en not_active Ceased
- 2010-09-27 PL PL10757604T patent/PL2483310T3/pl unknown
- 2010-09-27 HR HRP20141032AT patent/HRP20141032T1/hr unknown
- 2010-09-27 CN CN201080043541.2A patent/CN102574921B/zh not_active Expired - Fee Related
- 2010-09-27 DK DK10757604.3T patent/DK2483310T3/da active
- 2010-09-27 KR KR1020127007953A patent/KR101508043B1/ko not_active Expired - Fee Related
- 2010-09-27 BR BR112012006326A patent/BR112012006326A2/pt not_active Application Discontinuation
- 2010-09-27 WO PCT/EP2010/064209 patent/WO2011039126A1/en not_active Ceased
- 2010-09-27 JP JP2012531338A patent/JP5695059B2/ja not_active Expired - Fee Related
- 2010-09-27 SI SI201030786T patent/SI2483310T1/sl unknown
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