CA3132198A1 - Anti-cancer combination therapies comprising ctla-4 and pd-1 blocking agents - Google Patents
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- CA3132198A1 CA3132198A1 CA3132198A CA3132198A CA3132198A1 CA 3132198 A1 CA3132198 A1 CA 3132198A1 CA 3132198 A CA3132198 A CA 3132198A CA 3132198 A CA3132198 A CA 3132198A CA 3132198 A1 CA3132198 A1 CA 3132198A1
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- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
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Landscapes
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- Veterinary Medicine (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US201962817749P | 2019-03-13 | 2019-03-13 | |
| US62/817,749 | 2019-03-13 | ||
| PCT/US2020/021783 WO2020185722A2 (en) | 2019-03-13 | 2020-03-10 | Anti-cancer combination therapies comprising ctla-4 and pd-1 blocking agents |
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| CA3132198A1 true CA3132198A1 (en) | 2020-09-17 |
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| US (1) | US12358986B2 (en, 2012) |
| EP (1) | EP3937979A4 (en, 2012) |
| JP (1) | JP7581225B2 (en, 2012) |
| KR (1) | KR20210141539A (en, 2012) |
| CN (1) | CN113631189A (en, 2012) |
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| BR (1) | BR112021017892A8 (en, 2012) |
| CA (1) | CA3132198A1 (en, 2012) |
| MA (1) | MA55316A (en, 2012) |
| MX (1) | MX2021010997A (en, 2012) |
| WO (1) | WO2020185722A2 (en, 2012) |
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| JP7694922B2 (ja) * | 2021-01-29 | 2025-06-18 | ミンフィ ファーマシューティカル （ハンチョウ） リミテッド | 抗原結合タンパク質およびその使用 |
| IL307494A (en) * | 2021-04-14 | 2023-12-01 | Akeso Pharmaceuticals Inc | Use of antibody in anti-tumor treatment |
| TW202241512A (zh) * | 2021-04-21 | 2022-11-01 | 中國商和鉑醫藥（上海）有限責任公司 | 結合ctla-4的抗體及其用途 |
| KR20230110141A (ko) | 2022-01-14 | 2023-07-21 | 영남대학교 산학협력단 | PD-L1 단백질에 특이적으로 결합하는 Fab 단편 및 이의 용도 |
| EP4522654A1 (en) * | 2022-05-12 | 2025-03-19 | BioNTech SE | Monoclonal antibodies directed against programmed death-1 protein and their use in medicine |
| WO2025042997A1 (en) * | 2023-08-21 | 2025-02-27 | Agenus Inc. | Methods of treating colorectal cancer using a combination of a ctla-4 inhibitor and a pd-1 inhibitor |
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| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| US5885573A (en) | 1993-06-01 | 1999-03-23 | Arch Development Corporation | Methods and materials for modulation of the immunosuppressive activity and toxicity of monoclonal antibodies |
| US7109003B2 (en) | 1998-12-23 | 2006-09-19 | Abgenix, Inc. | Methods for expressing and recovering human monoclonal antibodies to CTLA-4 |
| KR100942863B1 (ko) | 1999-08-24 | 2010-02-17 | 메다렉스, 인코포레이티드 | 인간 씨티엘에이-4 항체 및 그의 용도 |
| US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
| US20060235208A1 (en) | 2002-09-27 | 2006-10-19 | Xencor, Inc. | Fc variants with optimized properties |
| AU2003279719B8 (en) | 2002-09-27 | 2009-01-08 | Xencor Inc. | Optimized Fc variants and methods for their generation |
| EP2418278A3 (en) | 2005-05-09 | 2012-07-04 | Ono Pharmaceutical Co., Ltd. | Human monoclonal antibodies to programmed death 1(PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapeutics |
| US8907065B2 (en) | 2006-12-15 | 2014-12-09 | Ablynx N.V. | Polypeptides that modulate the interaction between cells of the immune system |
| CA2855098C (en) | 2007-06-18 | 2018-02-27 | Merck Sharp & Dohme B.V. | Antibodies to human programmed death receptor pd-1 |
| CA2697032C (en) | 2007-08-22 | 2021-09-14 | The Regents Of The University Of California | Activatable binding polypeptides and methods of identification and use thereof |
| WO2009030285A1 (en) | 2007-09-07 | 2009-03-12 | Ablynx N.V. | Binding molecules with multiple binding sites, compositions comprising the same and uses thereof |
| EP2262837A4 (en) | 2008-03-12 | 2011-04-06 | Merck Sharp & Dohme | PD-1 BINDING PROTEINS |
| JP5851842B2 (ja) | 2009-01-12 | 2016-02-03 | サイトムエックス セラピューティクス, インク.CytomX Therapeutics, Inc. | 改変した抗体組成物、それを作製および使用する方法 |
| JP2013523098A (ja) | 2010-03-29 | 2013-06-17 | ザイムワークス，インコーポレイテッド | 強化又は抑制されたエフェクター機能を有する抗体 |
| PT2691417T (pt) | 2011-03-29 | 2018-10-31 | Roche Glycart Ag | Variantes de fc de anticorpos |
| HRP20190574T1 (hr) | 2012-12-03 | 2019-05-17 | Bristol-Myers Squibb Company | Poboljšanje anti-kancerogene aktivnosti imunomodulatornih fc fuzijskih proteina |
| JP6612214B2 (ja) | 2013-05-20 | 2019-11-27 | ジェネンテック， インコーポレイテッド | 抗トランスフェリン受容体抗体及び使用方法 |
| TWI681969B (zh) | 2014-01-23 | 2020-01-11 | 美商再生元醫藥公司 | 針對ｐｄ-１的人類抗體 |
| WO2015176033A1 (en) * | 2014-05-15 | 2015-11-19 | Bristol-Myers Squibb Company | Treatment of lung cancer using a combination of an anti-pd-1 antibody and another anti-cancer agent |
| CN105296433B (zh) | 2014-08-01 | 2018-02-09 | 中山康方生物医药有限公司 | 一种ctla4抗体、其药物组合物及其用途 |
| HRP20201756T8 (hr) | 2014-11-21 | 2021-08-20 | Bristol-Myers Squibb Company | Antitijela koja sadrže modificirane regije teškog lanca |
| US10196445B1 (en) | 2015-03-17 | 2019-02-05 | Bristol-Myers Squibb Company | Ipilimumab variant with enhanced ADCC |
| HUE050750T2 (hu) | 2015-05-29 | 2021-01-28 | Agenus Inc | CTLA-4 elleni antitestek és eljárások alkalmazásukra |
| CA3003777A1 (en) | 2015-11-18 | 2017-05-26 | Merck Sharp & Dohme Corp. | Pd1/ctla4 binders |
| US11072657B2 (en) * | 2015-11-18 | 2021-07-27 | Bristol-Myers Squibb Company | Treatment of lung cancer using a combination of an anti-PD-1 antibody and an anti-CTLA-4 antibody |
| JO3744B1 (ar) | 2015-11-18 | 2021-01-31 | Merck Sharp & Dohme | مواد ربط لـpd1 و/ أو lag3 |
| AU2016355569B2 (en) | 2015-11-18 | 2020-01-02 | Merck Sharp & Dohme Llc | CTLA4 binders |
| US10596257B2 (en) | 2016-01-08 | 2020-03-24 | Hoffmann-La Roche Inc. | Methods of treating CEA-positive cancers using PD-1 axis binding antagonists and anti-CEA/anti-CD3 bispecific antibodies |
| JP7039582B2 (ja) | 2016-11-03 | 2022-03-22 | ブリストル－マイヤーズ スクイブ カンパニー | 活性化可能な抗ｃｔｌａ－４抗体およびその使用 |
| JP2020512354A (ja) * | 2017-03-31 | 2020-04-23 | メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． | Ｐｄ−１のアンタゴニストと抗ｃｔｌａ４抗体との組み合わせでがんを処置するための組成物および方法 |
| MA50501A (fr) * | 2017-05-02 | 2020-09-09 | Merck Sharp & Dohme | Formulations stables d'anticorps anti-ctla4 seuls et en combinaison avec des anticorps anti-récepteur de mort programmée 1 (pd-1) et leurs procédés d'utilisation |
| JP2020522486A (ja) | 2017-06-01 | 2020-07-30 | サイトメックス セラピューティクス インコーポレイテッド | 活性化可能抗ｐｄｌ１抗体、およびその使用方法 |
| TWI799432B (zh) | 2017-07-27 | 2023-04-21 | 美商再生元醫藥公司 | 抗ctla-4抗體及其用途 |
| CN119792515A (zh) * | 2018-02-13 | 2025-04-11 | 默沙东有限责任公司 | 用抗pd-1抗体和抗ctla-4抗体治疗癌症的方法 |
-
2020
- 2020-03-10 MX MX2021010997A patent/MX2021010997A/es unknown
- 2020-03-10 CA CA3132198A patent/CA3132198A1/en active Pending
- 2020-03-10 JP JP2021553837A patent/JP7581225B2/ja active Active
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| MA55316A (fr) | 2022-01-19 |
| US20220411507A1 (en) | 2022-12-29 |
| KR20210141539A (ko) | 2021-11-23 |
| MX2021010997A (es) | 2021-10-01 |
| WO2020185722A2 (en) | 2020-09-17 |
| EP3937979A2 (en) | 2022-01-19 |
| BR112021017892A8 (pt) | 2023-01-31 |
| JP7581225B2 (ja) | 2024-11-12 |
| BR112021017892A2 (en, 2012) | 2021-12-07 |
| WO2020185722A3 (en) | 2020-11-12 |
| CN113631189A (zh) | 2021-11-09 |
| AU2020234785A1 (en) | 2021-08-19 |
| US12358986B2 (en) | 2025-07-15 |
| JP2022525071A (ja) | 2022-05-11 |
| EP3937979A4 (en) | 2023-03-08 |
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