JP6917902B2 - Ｃｔｌａ４に結合する抗体医薬 - Google Patents
Ｃｔｌａ４に結合する抗体医薬 Download PDFInfo
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| US20160075772A1 (en) | 2014-09-12 | 2016-03-17 | Regeneron Pharmaceuticals, Inc. | Treatment of Fibrodysplasia Ossificans Progressiva |
| WO2016130986A1 (en) * | 2015-02-13 | 2016-08-18 | Sorrento Therapeutics, Inc. | Antibody therapeutics that bind ctla4 |
| SI3303394T1 (sl) | 2015-05-29 | 2020-10-30 | Agenus Inc. | Protitelesa proti-CTLA-4 in postopki njihove uporabe |
| NZ739503A (en) | 2015-07-16 | 2023-06-30 | Bioxcel Therapeutics Inc | A novel approach for treatment of cancer using immunomodulation |
| US11542332B2 (en) | 2016-03-26 | 2023-01-03 | Bioatla, Inc. | Anti-CTLA4 antibodies, antibody fragments, their immunoconjugates and uses thereof |
| JP7461741B2 (ja) | 2016-06-20 | 2024-04-04 | カイマブ・リミテッド | 抗ｐｄ－ｌ１およびｉｌ－２サイトカイン |
| WO2018035710A1 (en) * | 2016-08-23 | 2018-03-01 | Akeso Biopharma, Inc. | Anti-ctla4 antibodies |
| JP6976322B2 (ja) * | 2016-10-10 | 2021-12-08 | クラウン バイオサイエンス，インコーポレイテッド（タイツァン） | 新規抗ｃｔｌａ４抗体 |
| IL266918B2 (en) | 2016-12-07 | 2024-03-01 | Agenus Inc | Anti-ctla-4 antibodies and methods of use thereof |
| EP3585430A4 (en) | 2017-02-21 | 2020-12-09 | REMD Biotherapeutics, Inc. | TREATMENT OF CANCER WITH ANTIBODIES THAT BIND TO T-CYTOTOXIC T-LYMPHOCYTES ANTIGEN-4 (CTLA-4) |
| CN108124445B (zh) * | 2017-03-15 | 2021-05-04 | 苏州银河生物医药有限公司 | Ctla4抗体、其药物组合物及其用途 |
| KR102372274B1 (ko) | 2017-05-19 | 2022-03-08 | 우시 바이올로직스 (상하이) 컴퍼니 리미티드 | 세포독성 t-림프구-관련 단백질 4 (ctla-4)에 대한 신규의 단일클론 항체 |
| 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 |
| WO2019036855A1 (en) | 2017-08-21 | 2019-02-28 | Adagene Inc. | Anti-cd137 molecules and use thereof |
| IL275391B2 (en) * | 2017-12-20 | 2025-05-01 | Harbour Biomed Shanghai Co Ltd | Antibodies binding ctla-4 and uses thereof |
| WO2019148444A1 (en) * | 2018-02-02 | 2019-08-08 | Adagene Inc. | Anti-ctla4 antibodies and methods of making and using the same |
| WO2019148445A1 (en) | 2018-02-02 | 2019-08-08 | Adagene Inc. | Precision/context-dependent activatable antibodies, and methods of making and using the same |
| JP2021525576A (ja) * | 2018-05-31 | 2021-09-27 | ソレント・セラピューティクス・インコーポレイテッドＳｏｒｒｅｎｔｏ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | リンパ系を標的化した薬物送達方法 |
| US20210236547A1 (en) * | 2018-06-05 | 2021-08-05 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Rapid production, expansion, and increased purity of car-t cells using beads with protein l |
| CN110760002A (zh) * | 2018-07-25 | 2020-02-07 | 南京金斯瑞生物科技有限公司 | 人源化抗人ctla4单克隆抗体及其制备方法和用途 |
| IL291545B1 (en) * | 2018-10-31 | 2025-09-01 | Bioatla Llc | Anti-CTLA4 antibodies, antibody fragments, immunoconjugates thereof and uses thereof |
| CN113614109A (zh) | 2018-12-21 | 2021-11-05 | Ose免疫疗法公司 | 双功能抗pd-1/il-7分子 |
| CA3123050A1 (en) | 2018-12-26 | 2020-07-02 | City Of Hope | Activatable masked anti-ctla4 binding proteins |
| CN119930820A (zh) * | 2018-12-27 | 2025-05-06 | 吉加根公司 | 抗ctla-4结合蛋白及其使用方法 |
| WO2020165374A1 (en) | 2019-02-14 | 2020-08-20 | Ose Immunotherapeutics | Bifunctional molecule comprising il-15ra |
| WO2021011480A1 (en) * | 2019-07-12 | 2021-01-21 | The Research Foundation For The State University Of New York | Compositions and methods to block and bind cxcr4 to modulate cellular function |
| WO2021122866A1 (en) | 2019-12-17 | 2021-06-24 | Ose Immunotherapeutics | Bifunctional molecules comprising an il-7 variant |
| EP4110810A1 (en) | 2020-02-28 | 2023-01-04 | Orega Biotech | Combination therapies based on ctla4 and il-17b inhibitors |
| MX2022015948A (es) * | 2020-07-02 | 2023-04-05 | Gigagen Inc | Proteínas de unión anti-ctla-4 y métodos de uso de estas. |
| WO2022112198A1 (en) | 2020-11-24 | 2022-06-02 | Worldwide Innovative Network | Method to select the optimal immune checkpoint therapies |
| WO2022214653A1 (en) | 2021-04-09 | 2022-10-13 | Ose Immunotherapeutics | New scaffold for bifunctional molecules with improved properties |
| EP4320156A1 (en) | 2021-04-09 | 2024-02-14 | Ose Immunotherapeutics | Scaffold for bifunctioanl molecules comprising pd-1 or cd28 and sirp binding domains |
| WO2024003360A1 (en) | 2022-07-01 | 2024-01-04 | Institut Curie | Biomarkers and uses thereof for the treatment of neuroblastoma |
| WO2024028386A1 (en) | 2022-08-02 | 2024-02-08 | Ose Immunotherapeutics | Multifunctional molecule directed against cd28 |
| WO2024200823A1 (en) | 2023-03-30 | 2024-10-03 | Ose Immunotherapeutics | Lipid-based nanoparticle targeted at activated immune cells for the expression of immune cell enhancing molecule and use thereof |
| WO2024200820A1 (en) | 2023-03-30 | 2024-10-03 | Ose Immunotherapeutics | Method of synthesis of targeted lipid nanoparticle and uses thereof |
| WO2025242835A1 (en) | 2024-05-22 | 2025-11-27 | Ose Immunotherapeutics | Molecules comprising masking linkers and uses thereof for the treatment of cancer |
Family Cites Families (48)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL154598B (nl) | 1970-11-10 | 1977-09-15 | Organon Nv | Werkwijze voor het aantonen en bepalen van laagmoleculire verbindingen en van eiwitten die deze verbindingen specifiek kunnen binden, alsmede testverpakking. |
| US3901654A (en) | 1971-06-21 | 1975-08-26 | Biological Developments | Receptor assays of biologically active compounds employing biologically specific receptors |
| US3817827A (en) | 1972-03-30 | 1974-06-18 | Scott Paper Co | Soft absorbent fibrous webs containing elastomeric bonding material and formed by creping and embossing |
| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| US4098876A (en) | 1976-10-26 | 1978-07-04 | Corning Glass Works | Reverse sandwich immunoassay |
| JPS6023084B2 (ja) | 1979-07-11 | 1985-06-05 | 味の素株式会社 | 代用血液 |
| US4640835A (en) | 1981-10-30 | 1987-02-03 | Nippon Chemiphar Company, Ltd. | Plasminogen activator derivatives |
| US4496689A (en) | 1983-12-27 | 1985-01-29 | Miles Laboratories, Inc. | Covalently attached complex of alpha-1-proteinase inhibitor with a water soluble polymer |
| EP0206448B1 (en) | 1985-06-19 | 1990-11-14 | Ajinomoto Co., Inc. | Hemoglobin combined with a poly(alkylene oxide) |
| US4791192A (en) | 1986-06-26 | 1988-12-13 | Takeda Chemical Industries, Ltd. | Chemically modified protein with polyethyleneglycol |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| US6010902A (en) | 1988-04-04 | 2000-01-04 | Bristol-Meyers Squibb Company | Antibody heteroconjugates and bispecific antibodies for use in regulation of lymphocyte activity |
| US5859205A (en) * | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| GB9014932D0 (en) | 1990-07-05 | 1990-08-22 | Celltech Ltd | Recombinant dna product and method |
| JP3051145B2 (ja) | 1990-08-28 | 2000-06-12 | 住友製薬株式会社 | 新規なポリエチレングリコール誘導体修飾ペプチド |
| US5582996A (en) | 1990-12-04 | 1996-12-10 | The Wistar Institute Of Anatomy & Biology | Bifunctional antibodies and method of preparing same |
| DE4118120A1 (de) | 1991-06-03 | 1992-12-10 | Behringwerke Ag | Tetravalente bispezifische rezeptoren, ihre herstellung und verwendung |
| WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
| US5851795A (en) | 1991-06-27 | 1998-12-22 | Bristol-Myers Squibb Company | Soluble CTLA4 molecules and uses thereof |
| US6887471B1 (en) * | 1991-06-27 | 2005-05-03 | Bristol-Myers Squibb Company | Method to inhibit T cell interactions with soluble B7 |
| JPH05244982A (ja) | 1991-12-06 | 1993-09-24 | Sumitomo Chem Co Ltd | 擬人化ｂ−ｂ１０ |
| JP3589665B2 (ja) | 1992-10-23 | 2004-11-17 | イミュネックス・コーポレーション | 可溶性オリゴマー蛋白質の調製法 |
| US5932462A (en) | 1995-01-10 | 1999-08-03 | Shearwater Polymers, Inc. | Multiarmed, monofunctional, polymer for coupling to molecules and surfaces |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| GB9722131D0 (en) | 1997-10-20 | 1997-12-17 | Medical Res Council | Method |
| US20020142374A1 (en) | 1998-08-17 | 2002-10-03 | Michael Gallo | Generation of modified molecules with increased serum half-lives |
| SI2112166T1 (sl) * | 1998-12-23 | 2019-05-31 | Pfizer Inc. | Človeška monoklonska protitelesa proti CTLA-4 |
| CN1371416B (zh) * | 1999-08-24 | 2012-10-10 | 梅达里克斯公司 | 人ctla-4抗体及其应用 |
| GB9928787D0 (en) | 1999-12-03 | 2000-02-02 | Medical Res Council | Direct screening method |
| AU2001233027A1 (en) * | 2000-01-27 | 2001-08-07 | Genetics Institute, Llc | Antibodies against ctla4 (cd152), conjugates comprising same, and uses thereof |
| MXPA02012434A (es) * | 2000-06-16 | 2004-09-06 | Cambridge Antibody Tech | Anticuerpos que se unen inmunoespecificamente a estimulador de linfocitos ii. |
| US6938003B2 (en) | 2000-06-30 | 2005-08-30 | Mahesh Harpale | Method and apparatus for a credibility reporting system to augment an online exchange |
| GB0025144D0 (en) | 2000-10-13 | 2000-11-29 | Medical Res Council | Concatenated nucleic acid sequences |
| IL149701A0 (en) * | 2001-05-23 | 2002-11-10 | Pfizer Prod Inc | Use of anti-ctla-4 antibodies |
| BR0309254A (pt) * | 2002-04-12 | 2005-03-01 | Medarex Inc | Uso de um anticorpo anti-ctla-4 |
| MXPA05005921A (es) * | 2002-12-02 | 2005-10-19 | Abgenix Inc | Anticuerpos dirigidos a factor de necrosis tumoral y sus usos. |
| US20040202995A1 (en) | 2003-04-09 | 2004-10-14 | Domantis | Nucleic acids, proteins, and screening methods |
| KR100845354B1 (ko) * | 2004-03-26 | 2008-07-09 | 화이자 프로덕츠 인코포레이티드 | 항－ｃｔｌａ－4 항체의 용도 |
| ES2426725T3 (es) * | 2004-05-27 | 2013-10-24 | Crucell Holland B.V. | Método para identificar moléculas de unión que pueden neutralizar el virus de la rabia |
| CN101146552A (zh) * | 2005-03-23 | 2008-03-19 | 辉瑞产品有限公司 | 用ctla4抗体和激素疗法治疗前列腺癌 |
| WO2006101692A1 (en) * | 2005-03-23 | 2006-09-28 | Pfizer Products Inc. | Anti-ctla4 antibody and indolinone combination therapy for treatment of cancer |
| EP2240204A1 (en) * | 2008-02-04 | 2010-10-20 | Medarex, Inc. | Anti-clta-4 antibodies with reduced blocking of binding of ctla-4 to b7 and uses thereof |
| EA023148B1 (ru) * | 2008-08-25 | 2016-04-29 | Эмплиммьюн, Инк. | Композиции на основе антагонистов pd-1 и их применение |
| EP2679681B2 (en) * | 2011-02-25 | 2023-11-15 | Chugai Seiyaku Kabushiki Kaisha | FcgammaRIIB-specific FC antibody |
| GB201103955D0 (en) * | 2011-03-09 | 2011-04-20 | Antitope Ltd | Antibodies |
| PT2900694T (pt) * | 2012-09-27 | 2018-11-13 | Merus Nv | Anticorpos de igg biespecíficos como ativadores de células t |
| WO2016130986A1 (en) * | 2015-02-13 | 2016-08-18 | Sorrento Therapeutics, Inc. | Antibody therapeutics that bind ctla4 |
| US20170233476A1 (en) * | 2016-02-12 | 2017-08-17 | Sorrento Therapeutics, Inc. | Antibody Therapeutics That Bind CTLA4 |
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