CA2859767C - Bispecific antibody molecule and use thereof for treatment of proliferative disease - Google Patents
Bispecific antibody molecule and use thereof for treatment of proliferative disease Download PDFInfo
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- CA2859767C CA2859767C CA2859767A CA2859767A CA2859767C CA 2859767 C CA2859767 C CA 2859767C CA 2859767 A CA2859767 A CA 2859767A CA 2859767 A CA2859767 A CA 2859767A CA 2859767 C CA2859767 C CA 2859767C
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Landscapes
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106999556A (zh) * | 2014-07-21 | 2017-08-01 | 武汉友芝友生物制药有限公司 | 细胞因子诱导的杀伤细胞的双特异性抗体介导的癌症治疗 |
Families Citing this family (169)
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| US20090162359A1 (en) | 2007-12-21 | 2009-06-25 | Christian Klein | Bivalent, bispecific antibodies |
| US9676845B2 (en) | 2009-06-16 | 2017-06-13 | Hoffmann-La Roche, Inc. | Bispecific antigen binding proteins |
| EP2647707B1 (en) | 2010-11-30 | 2018-09-12 | Chugai Seiyaku Kabushiki Kaisha | Cytotoxicity-inducing therapeutic agent |
| RU2607038C2 (ru) | 2011-02-28 | 2017-01-10 | Ф. Хоффманн-Ля Рош Аг | Антигенсвязывающие белки |
| CN103403025B (zh) | 2011-02-28 | 2016-10-12 | 弗·哈夫曼-拉罗切有限公司 | 单价抗原结合蛋白 |
| RU2632647C2 (ru) | 2011-04-22 | 2017-10-06 | Аптево Рисерч Энд Девелопмент Ллс | Белки, связывающие специфический мембранный антиген простаты, и соответствующие композиции и способы |
| US12466897B2 (en) | 2011-10-10 | 2025-11-11 | Xencor, Inc. | Heterodimeric human IgG1 polypeptides with isoelectric point modifications |
| DK2794658T3 (en) * | 2011-12-19 | 2017-06-19 | Synimmune Gmbh | BISPECIFIC ANTIBODY MOLECULE |
| WO2014076292A1 (en) * | 2012-11-19 | 2014-05-22 | Baliopharm Ag | Recombinant bispecific antibody binding to cd20 and cd95 |
| CA2898100C (en) | 2013-01-14 | 2023-10-10 | Xencor, Inc. | Novel heterodimeric proteins |
| EP2958942B1 (en) | 2013-02-20 | 2020-06-03 | Novartis AG | Effective targeting of primary human leukemia using anti-cd123 chimeric antigen receptor engineered t cells |
| US10858417B2 (en) | 2013-03-15 | 2020-12-08 | Xencor, Inc. | Heterodimeric proteins |
| HRP20251426T1 (hr) | 2013-05-06 | 2026-01-02 | Scholar Rock, Inc. | Sastavi i postupci za modulaciju faktora rasta |
| EP4067383A1 (en) | 2013-07-25 | 2022-10-05 | Cytomx Therapeutics Inc. | Multispecific antibodies, multispecific activatable antibodies and methods of using the same |
| EP2839842A1 (en) * | 2013-08-23 | 2015-02-25 | MacroGenics, Inc. | Bi-specific monovalent diabodies that are capable of binding CD123 and CD3 and uses thereof |
| RU2016115866A (ru) * | 2013-10-11 | 2017-11-16 | Ф. Хоффманн-Ля Рош Аг | Мультиспецифические антитела с обменянными доменами и одинаковыми вариабельными доменами легкой цепи |
| KR20230004939A (ko) * | 2014-02-07 | 2023-01-06 | 맥마스터 유니버시티 | 3기능성 t 세포-항원 커플러 및 이의 제조 방법 및 용도 |
| CN106062193B (zh) * | 2014-02-28 | 2020-08-25 | 安斯泰来制药株式会社 | 与人tlr2及人tlr4结合的双特异性抗体 |
| EP3725812B1 (en) * | 2014-03-03 | 2023-09-27 | Academia Sinica | Bi-specific antibodies and uses thereof |
| US11485790B2 (en) | 2014-04-07 | 2022-11-01 | Chugai Seiyaku Kabushiki Kaisha | Immunoactivating antigen-binding molecule |
| MX2016014434A (es) | 2014-05-13 | 2017-02-23 | Chugai Pharmaceutical Co Ltd | Molecula de union a antigeno redirigida a celulas t para celulas que tienen funcion de inmunosupresion. |
| CA2952727A1 (en) * | 2014-06-27 | 2015-12-30 | Innate Pharma | Multispecific nkp46 binding proteins |
| PE20170286A1 (es) | 2014-07-01 | 2017-03-30 | Pfizer | Diacuerpos heterodimericos biespecificos y sus usos |
| CN104558192B (zh) * | 2015-01-21 | 2018-12-28 | 武汉友芝友生物制药有限公司 | 一种双特异性抗体her2xcd3的构建及应用 |
| MX2017001011A (es) | 2014-07-21 | 2018-05-28 | Novartis Ag | Tratamiento de cancer de usando un receptor quimerico de antigeno anti-bcma. |
| KR20170037625A (ko) | 2014-07-21 | 2017-04-04 | 노파르티스 아게 | Cll-1 키메라 항원 수용체를 사용한 암의 치료 |
| WO2016014974A2 (en) | 2014-07-25 | 2016-01-28 | Cytomx Therapeutics, Inc. | Anti-cd3 antibodies, activatable anti-cd3 antibodies, multispecific anti-cd3 antibodies, multispecific activatable anti-cd3 antibodies, and methods of using the same |
| EP2985294A1 (en) | 2014-08-14 | 2016-02-17 | Deutsches Krebsforschungszentrum | Recombinant antibody molecule and its use for target cell restricted T cell activation |
| AU2015305531B2 (en) | 2014-08-19 | 2021-05-20 | Novartis Ag | Anti-CD123 chimeric antigen receptor (CAR) for use in cancer treatment |
| EP3191526B1 (en) | 2014-09-12 | 2023-02-22 | The Board of Trustees of the Leland Stanford Junior University | Wnt signaling agonist molecules |
| WO2016077638A1 (en) * | 2014-11-12 | 2016-05-19 | Memorial Sloan Kettering Cancer Center | Anti-chondroitin sulfate proteoglycan 4 antibodies and uses thereof |
| US9879087B2 (en) | 2014-11-12 | 2018-01-30 | Siamab Therapeutics, Inc. | Glycan-interacting compounds and methods of use |
| IL278574B2 (en) | 2014-11-12 | 2024-11-01 | Seagen Inc | Glycan-interacting compounds and methods of use |
| US10259887B2 (en) | 2014-11-26 | 2019-04-16 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and tumor antigens |
| MX2017006918A (es) | 2014-11-26 | 2018-01-25 | Xencor Inc | Anticuerpos heterodimericos que se unen a cd3 y cd38. |
| CN110894240B (zh) | 2014-11-26 | 2022-04-15 | 森科股份有限公司 | 结合cd3和肿瘤抗原的异二聚体抗体 |
| EP3029067A1 (en) | 2014-12-01 | 2016-06-08 | Deutsches Krebsforschungszentrum | Use of blocking-reagents for reducing unspecific T cell-activation |
| HRP20250129T1 (hr) | 2014-12-15 | 2025-04-11 | The Regents Of The University Of California | Bispecifični or-gate kimerni antigenski receptor koji reagira na cd19 i cd20 |
| EP3237005B1 (en) * | 2014-12-22 | 2024-09-18 | Systimmune, Inc. | Bispecific tetravalent antibodies and methods of making and using thereof |
| CN105821029A (zh) * | 2015-01-04 | 2016-08-03 | 彭霞 | 异源融合基因修饰的癌细胞/树突状细胞融合肿瘤疫苗及其制备方法 |
| CN104774268B (zh) * | 2015-01-21 | 2018-09-28 | 武汉友芝友生物制药有限公司 | 一种双特异性抗体egfr×cd3的构建及应用 |
| CN104558193B (zh) * | 2015-01-21 | 2019-01-11 | 武汉友芝友生物制药有限公司 | 一种靶向鼠t淋巴细胞cd3和人肿瘤抗原her2的双特异性抗体制备方法及应用 |
| CN104628866B (zh) * | 2015-01-21 | 2018-03-27 | 中国药科大学 | 一种靶向vegfr2的抗体融合蛋白的制备及其用途 |
| CN104592391B (zh) * | 2015-01-21 | 2020-08-21 | 武汉友芝友生物制药有限公司 | 一种双特异性抗体EpCAM×CD3的构建及应用 |
| CN104788567B (zh) * | 2015-01-21 | 2019-03-26 | 武汉友芝友生物制药有限公司 | 一种靶向鼠T淋巴细胞CD3和人肿瘤抗原EpCAM的双特异性抗体制备方法及应用 |
| CN104592395B (zh) * | 2015-01-27 | 2017-11-14 | 中国药科大学 | Vegfr2单链抗体与mica融合蛋白的制备方法及用途 |
| WO2016207867A1 (en) | 2015-02-25 | 2016-12-29 | Université Du Luxembourg | Nat8l and n-acetylaspartate in cancer |
| EP3064507A1 (en) | 2015-03-06 | 2016-09-07 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Fusion proteins comprising a binding protein and an interleukin-15 polypeptide having a reduced affinity for IL15ra and therapeutic uses thereof |
| WO2016166139A1 (en) | 2015-04-14 | 2016-10-20 | Eberhard Karls Universität Tübingen | Bispecific fusion proteins for enhancing immune responses of lymphocytes against tumor cells |
| WO2016178996A1 (en) | 2015-05-01 | 2016-11-10 | The Regents Of The University Of California | Glycan-dependent immunotherapeutic molecules |
| CN115109158A (zh) | 2015-05-07 | 2022-09-27 | 阿吉纳斯公司 | 抗ox40抗体及其使用方法 |
| US20180194861A1 (en) * | 2015-07-10 | 2018-07-12 | Abbvie Inc. | IgM- or IgE-Modified Binding Proteins and Uses Thereof |
| TWI829617B (zh) * | 2015-07-31 | 2024-01-21 | 德商安美基研究（慕尼黑）公司 | Ｆｌｔ３及ｃｄ３抗體構築體 |
| TWI796283B (zh) | 2015-07-31 | 2023-03-21 | 德商安美基研究（慕尼黑）公司 | Ｍｓｌｎ及ｃｄ３抗體構築體 |
| EA039859B1 (ru) * | 2015-07-31 | 2022-03-21 | Эмджен Рисерч (Мюник) Гмбх | Биспецифические конструкты антител, связывающие egfrviii и cd3 |
| TWI744242B (zh) | 2015-07-31 | 2021-11-01 | 德商安美基研究（慕尼黑）公司 | Egfrviii及cd3抗體構築體 |
| CN107106682B (zh) | 2015-08-26 | 2021-05-25 | 比森医疗股份有限公司 | 多特异性抗体平台和相关方法 |
| LU92815B1 (en) | 2015-09-04 | 2017-03-20 | Univ Luxembourg | Inhibitor of dj-1 for therapy |
| CN108367004B (zh) | 2015-09-21 | 2022-09-13 | 阿帕特夫研究和发展有限公司 | Cd3结合多肽 |
| AR106188A1 (es) | 2015-10-01 | 2017-12-20 | Hoffmann La Roche | Anticuerpos anti-cd19 humano humanizados y métodos de utilización |
| WO2017055398A2 (en) | 2015-10-02 | 2017-04-06 | F. Hoffmann-La Roche Ag | Bispecific antibodies specific for a costimulatory tnf receptor |
| CR20180171A (es) * | 2015-10-07 | 2018-05-03 | Hoffmann La Roche | Anticuerpos biespecíficos con tetravalencia para un receptor de fnt coestimulador |
| WO2017066136A2 (en) * | 2015-10-13 | 2017-04-20 | Eureka Therapeutics, Inc. | Antibody agents specific for human cd19 and uses thereof |
| BR112018009004A8 (pt) | 2015-11-03 | 2019-02-26 | Ambrx Inc | conjugados anti-cd3-folato e seus usos |
| EP3373969A4 (en) | 2015-11-12 | 2019-08-14 | Siamab Therapeutics, Inc. | GLYCANINTERAGING COMPOUNDS AND METHOD OF USE |
| EP3374389A1 (en) * | 2015-11-13 | 2018-09-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Anti- nkg2d single domain antibodies and uses thereof |
| EP3378488A4 (en) | 2015-11-18 | 2019-10-30 | Chugai Seiyaku Kabushiki Kaisha | METHOD FOR IMPROVING THE HUMORAL IMMUNE REACTION |
| 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 |
| WO2017096179A1 (en) | 2015-12-02 | 2017-06-08 | Agenus Inc. | Antibodies and methods of use thereof |
| EP3192810A1 (en) * | 2016-01-14 | 2017-07-19 | Deutsches Krebsforschungszentrum | Psma binding antibody and uses thereof |
| CN114716557A (zh) | 2016-02-03 | 2022-07-08 | 安进研发（慕尼黑）股份有限公司 | Psma和cd3双特异性t细胞接合抗体构建体 |
| WO2017158339A1 (en) * | 2016-03-15 | 2017-09-21 | Cancer Research Technology Limited | Antibodies and related molecules and uses thereof |
| JP7082604B2 (ja) * | 2016-03-21 | 2022-06-08 | マレンゴ・セラピューティクス，インコーポレーテッド | 多重特異性および多機能性分子ならびにその使用 |
| US11104738B2 (en) | 2016-04-04 | 2021-08-31 | Hemogenyx Pharmaceuticals Llc | Monoclonal antibodies to human FLT3/FLK2 receptor protein |
| EP3439699A4 (en) | 2016-04-04 | 2019-11-20 | Hemogenyx LLC | METHOD FOR ELIMINATING HEMATOPOETIC STEM CELLS / HEMATOPOIDIC PRECURSOR CELLS (HSC / HP) IN A PATIENT WITH BI-SPECIFIC ANTIBODIES |
| EP4050032A1 (en) | 2016-06-28 | 2022-08-31 | Xencor, Inc. | Heterodimeric antibodies that bind somatostatin receptor 2 |
| CN107556388A (zh) * | 2016-06-30 | 2018-01-09 | 中国科学院深圳先进技术研究院 | 抗CD44v6和CD3特异性双靶向抗体、含该双靶向抗体表达盒的微环DNA及应用 |
| GB201611530D0 (en) * | 2016-07-01 | 2016-08-17 | Alligator Bioscience Ab | Novel polypeptides |
| CN106632681B (zh) | 2016-10-11 | 2017-11-14 | 北京东方百泰生物科技有限公司 | 抗egfr和抗cd3双特异抗体及其应用 |
| WO2018071913A2 (en) * | 2016-10-14 | 2018-04-19 | Dana-Farber Cancer Institute, Inc. | Modular tetrameric bispecific antibody platform |
| WO2018089628A1 (en) | 2016-11-09 | 2018-05-17 | Agenus Inc. | Anti-ox40 antibodies, anti-gitr antibodies, and methods of use thereof |
| WO2018094143A1 (en) | 2016-11-17 | 2018-05-24 | Siamab Therapeutics, Inc. | Glycan-interacting compounds and methods of use |
| JP7350313B2 (ja) | 2016-12-16 | 2023-09-26 | ブルーフィン バイオメディシン， インコーポレイテッド | 抗ｃｕｂドメイン含有タンパク質１（ｃｄｃｐ１）抗体、抗体薬物コンジュゲート、およびその使用方法 |
| BR112019013189A2 (pt) | 2017-01-03 | 2019-12-10 | Hoffmann La Roche | moléculas de ligação ao antígeno biespecífica, polinucleotídeo, célula hospedeira, método de produção da molécula de ligação ao antígeno biespecífica, composição farmacêutica, uso, métodos para inibir o crescimento de células tumorais em um indivíduo e para tratar o câncer ou uma doença infecciosa |
| CA3053010A1 (en) * | 2017-02-08 | 2018-08-16 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins for activation of natural killer cells and therapeutic uses thereof to treat cancer |
| US20200095327A1 (en) * | 2017-02-08 | 2020-03-26 | Dragonfly Therapeutics, Inc. | Antibody heavy chain variable domains targeting the nkg2d receptor |
| CA3054079A1 (en) | 2017-02-20 | 2018-08-23 | Dragonfly Therapeutics, Inc. | Proteins binding her2, nkg2d and cd16 |
| BR112019018043A2 (pt) | 2017-03-03 | 2020-04-07 | Seattle Genetics Inc | método de tratamento de câncer, e, conjugado de anticorpo-fármaco |
| CN113603780B (zh) * | 2017-03-28 | 2022-07-01 | 礼进生物医药科技（上海）有限公司 | 用于增强肿瘤微环境中免疫应答的治疗剂和方法 |
| EP3601345A1 (en) * | 2017-03-29 | 2020-02-05 | H. Hoffnabb-La Roche Ag | Bispecific antigen binding molecule for a costimulatory tnf receptor |
| CN110382542B (zh) | 2017-03-29 | 2023-06-09 | 豪夫迈·罗氏有限公司 | 针对共刺激性tnf受体的双特异性抗原结合分子 |
| JP7381345B2 (ja) * | 2017-05-16 | 2023-11-15 | ザ・ジョンズ・ホプキンス・ユニバーシティ | Ｍａｎａボディおよび使用方法 |
| CN108948195B (zh) * | 2017-05-23 | 2022-05-31 | 胡毅 | 一种抗egfr/pd-l1双靶向抗体、其制备方法及用途 |
| CA3064714A1 (en) * | 2017-05-23 | 2018-11-29 | Dragonfly Therapeutics, Inc. | A protein binding nkg2d, cd16 and a tumor-associated antigen |
| KR102693777B1 (ko) * | 2017-06-02 | 2024-08-08 | 화이자 인코포레이티드 | Flt3에 특이적인 항체 및 이의 용도 |
| CN119899277A (zh) * | 2017-06-02 | 2025-04-29 | 辉瑞公司 | 靶向flt3的嵌合抗原受体 |
| WO2019023097A1 (en) * | 2017-07-26 | 2019-01-31 | Smet Pharmaceutical Inc | ASYMMETRIC BISPECIFIC ANTIBODIES AND THEIR USE |
| EA202090387A1 (ru) * | 2017-07-31 | 2020-05-21 | Драгонфлай Терапьютикс, Инк. | Белки, связывающие nkg2d, cd16 и flt3 |
| JP2020533002A (ja) | 2017-09-13 | 2020-11-19 | ラディミューン セラピュティックス， インク．Ｒａｄｉｍｍｕｎｅ Ｔｈｅｒａｐｅｕｔｉｃｓ， Ｉｎｃ． | メラニン抗体及びその使用 |
| AU2018348093A1 (en) * | 2017-10-10 | 2020-05-28 | Sanofi | Anti-CD38 antibodies and combinations with anti-CD3 and anti-CD28 antibodies |
| AU2018349093A1 (en) | 2017-10-12 | 2020-05-28 | Mcmaster University | T cell-antigen coupler with Y182T mutation and methods and uses thereof |
| BR112020007309A2 (pt) | 2017-10-14 | 2020-09-29 | Cytomx Therapeutics, Inc. | anticorpos, anticorpos ativáveis, anticorpos biespecíficos e anticorpos ativáveis biespecíficos e métodos de uso dos mesmos |
| US11312770B2 (en) | 2017-11-08 | 2022-04-26 | Xencor, Inc. | Bispecific and monospecific antibodies using novel anti-PD-1 sequences |
| CN111655729B (zh) | 2017-12-19 | 2023-10-20 | 瑟罗泽恩奥普瑞汀公司 | 抗卷曲蛋白抗体和使用方法 |
| AU2018393076B2 (en) | 2017-12-19 | 2025-11-20 | Surrozen Operating, Inc. | Anti-LRP5/6 antibodies and methods of use |
| WO2019126398A1 (en) | 2017-12-19 | 2019-06-27 | Surrozen, Inc. | Wnt surrogate molecules and uses thereof |
| WO2019139987A1 (en) | 2018-01-09 | 2019-07-18 | Elstar Therapeutics, Inc. | Calreticulin binding constructs and engineered t cells for the treatment of diseases |
| JP2021512914A (ja) | 2018-02-08 | 2021-05-20 | ドラゴンフライ セラピューティクス， インコーポレイテッド | ナチュラルキラー細胞を活性化する多特異的結合タンパク質を伴うがんの併用療法 |
| DK3749346T3 (da) | 2018-02-08 | 2024-09-09 | Dragonfly Therapeutics Inc | Antistof variable domænekombinationer rettet mod nkg2d-receptoren |
| SG11202007945UA (en) | 2018-02-20 | 2020-09-29 | Dragonfly Therapeutics Inc | Multi-specific binding proteins that bind cd33, nkg2d, and cd16, and methods of use |
| JP7288913B2 (ja) | 2018-03-14 | 2023-06-08 | アフィメッド ゲゼルシャフト ミット ベシュレンクテル ハフツンク | 二重特異性ｅｇｆｒ／ｃｄ１６抗原結合タンパク質 |
| US12152073B2 (en) | 2018-03-14 | 2024-11-26 | Marengo Therapeutics, Inc. | Multifunctional molecules that bind to calreticulin and uses thereof |
| EP3773911A2 (en) | 2018-04-04 | 2021-02-17 | Xencor, Inc. | Heterodimeric antibodies that bind fibroblast activation protein |
| AU2019271263A1 (en) * | 2018-05-16 | 2020-12-03 | Dragonfly Therapeutics, Inc. | Protein binding NKG2D, CD16 and a fibroblast activation protein |
| EP3796977A4 (en) * | 2018-05-17 | 2022-03-02 | The Board of Trustees of the Leland Stanford Junior University | RECEPTOR INHIBITION BY PHOSPHATASE RECRUITMENT |
| EA202091977A1 (ru) * | 2018-05-28 | 2021-02-09 | Драгонфлай Терапьютикс, Инк. | Мультиспецифические связывающие белки, которые связывают cd33, nkg2d и cd16, и способы применения |
| CN110540593B (zh) * | 2018-05-29 | 2022-05-17 | 上海药明生物技术有限公司 | 新型的抗cd3/抗cd20双特异性抗体 |
| MX2020013443A (es) | 2018-06-13 | 2021-02-26 | Novartis Ag | Receptores de antigeno quimerico de bcma y usos de los mismos. |
| US12473360B2 (en) | 2018-06-14 | 2025-11-18 | Bioatla, Inc. | Multi-specific antibody constructs |
| WO2019243564A1 (en) | 2018-06-21 | 2019-12-26 | Technische Universitaet Muenchen | Hepatitis b and/or hepatitis d-permissive cells and animals |
| CN112955465A (zh) | 2018-07-03 | 2021-06-11 | 马伦戈治疗公司 | 抗tcr抗体分子及其用途 |
| CN112689642B (zh) * | 2018-07-17 | 2025-01-17 | 特拉姆维拉免疫美国有限公司 | 具有各种不同的构建物优化的t细胞抗原偶联物 |
| US10640562B2 (en) | 2018-07-17 | 2020-05-05 | Mcmaster University | T cell-antigen coupler with various construct optimizations |
| US11110123B2 (en) | 2018-07-17 | 2021-09-07 | Triumvira Immunologics Usa, Inc. | T cell-antigen coupler with various construct optimizations |
| KR20250112921A (ko) | 2018-08-08 | 2025-07-24 | 드래곤플라이 쎄라퓨틱스, 인크. | Nkg2d, cd16 및 종양 관련 항원에 결합하는 단백질 |
| EA202091888A1 (ru) | 2018-08-08 | 2020-10-23 | Драгонфлай Терапьютикс, Инк. | Вариабельные домены антител, нацеленные на рецептор nkg2d |
| WO2020033630A1 (en) | 2018-08-08 | 2020-02-13 | Dragonfly Therapeutics, Inc. | Multi-specific binding proteins that bind bcma, nkg2d and cd16, and methods of use |
| EP3847196A4 (en) | 2018-09-07 | 2023-01-04 | ITabMed (HK) Limited | BISPECIFIC ANTIGEN BINDING PROTEINS AND USES THEREOF |
| EP3849538A4 (en) | 2018-09-10 | 2022-06-29 | Mirati Therapeutics, Inc. | Combination therapies |
| MY205658A (en) * | 2018-09-11 | 2024-11-04 | Deutsches Krebsforschungszentrumstiftung Des Ffentlichen Rechts | Improved anti-flt₃ antigen binding proteins |
| EP3623383A1 (en) | 2018-09-11 | 2020-03-18 | Deutsches Krebsforschungszentrum, Stiftung des öffentlichen Rechts | Improved bispecific flt3xcd3 antigen binding proteins |
| WO2020102233A1 (en) * | 2018-11-13 | 2020-05-22 | Jn Biosciences Llc | Bispecific antibodies for activation of immune cells |
| MY198034A (en) * | 2018-12-21 | 2023-07-27 | Hoffmann La Roche | Tumor-targeted agonistic cd28 antigen binding molecules |
| WO2020132810A1 (en) * | 2018-12-24 | 2020-07-02 | Generon (Shanghai) Corporation Ltd. | Multispecific antigen binding proteins capable of binding cd19 and cd3, and use thereof |
| CN114026122B (zh) | 2019-02-21 | 2024-12-31 | 马伦戈治疗公司 | 结合t细胞相关癌细胞的多功能分子及其用途 |
| CN119039441A (zh) | 2019-02-21 | 2024-11-29 | 马伦戈治疗公司 | 与nkp30结合的抗体分子及其用途 |
| CN109776683B (zh) * | 2019-03-19 | 2020-04-07 | 益科思特(北京)医药科技发展有限公司 | 一种双特异性抗体及其制备方法与应用 |
| US11912767B2 (en) | 2019-03-22 | 2024-02-27 | Regeneron Pharmaceuticals, Inc. | EGFR × CD28 multispecific antibodies |
| BR112021022135A2 (pt) * | 2019-05-06 | 2023-02-28 | Univ Brown | Anticorpos biespecíficos contra chi3l1 e pd1 com efeitos citotóxicos mediados por célula t realçados sobre células de tumor |
| JOP20210297A1 (ar) | 2019-05-08 | 2023-01-30 | Janssen Biotech Inc | مواد وطرق لحث المناعة التي تساهم فيها الخلايا التائية |
| MX2022004430A (es) * | 2019-10-15 | 2022-07-19 | Dragonfly Therapeutics Inc | Proteinas que se unen al receptor activador de celulas asesinas naturales grupo 2 miembro d (nkg2d), al cumulo de diferenciacion 16 (cd16) y a la tirosina cinasa 3 similar a fms (flt3). |
| EP3822288A1 (en) | 2019-11-18 | 2021-05-19 | Deutsches Krebsforschungszentrum, Stiftung des öffentlichen Rechts | Antibodies targeting, and other modulators of, the cd276 antigen, and uses thereof |
| CN116234829A (zh) | 2020-01-03 | 2023-06-06 | 马伦戈治疗公司 | 抗tcr抗体分子及其用途 |
| BR112022013633A2 (pt) * | 2020-01-09 | 2022-09-13 | Biomunex Pharmaceuticals | Anticorpos multiespecíficos que ligam tanto células mait quanto tumorais |
| CN113088495B (zh) * | 2020-01-09 | 2024-08-16 | 苏州方德门达新药开发有限公司 | 工程改造的t细胞、其制备及应用 |
| TWI869528B (zh) | 2020-01-13 | 2025-01-11 | 美商威特拉公司 | C5ar1抗體分子及其用途 |
| CN115605512A (zh) * | 2020-03-13 | 2023-01-13 | 詹森生物科技公司（Us） | 用于调节δ链介导的免疫的材料和方法 |
| US20240239912A1 (en) * | 2020-04-10 | 2024-07-18 | The Board Of Trustees Of The Leland Stanford Junior University | Targeted reduction of activated immune cells |
| BR112022021884A2 (pt) | 2020-05-06 | 2022-12-20 | Dragonfly Therapeutics Inc | Proteínas que se ligam a nkg2d, cd16 e clec12a |
| WO2021231976A1 (en) | 2020-05-14 | 2021-11-18 | Xencor, Inc. | Heterodimeric antibodies that bind prostate specific membrane antigen (psma) and cd3 |
| GB2595299B (en) | 2020-05-21 | 2022-08-03 | Mabsolve Ltd | Modified immunoglobulin FC regions |
| IL297880A (en) * | 2020-06-23 | 2023-01-01 | Hoffmann La Roche | Agonistic cd28 antigen binding molecules targeting her2 |
| KR102607909B1 (ko) * | 2020-08-19 | 2023-12-01 | 젠코어 인코포레이티드 | 항-cd28 조성물 |
| UY39488A (es) | 2020-10-28 | 2022-04-29 | Janssen Biotech Inc | Composiciones y métodos para modular la inmunidad mediada por la cadena delta gamma |
| AU2021368272A1 (en) * | 2020-11-02 | 2023-06-08 | Attralus, Inc. | Sap fc fusion proteins and methods of use |
| KR20230098317A (ko) | 2020-11-03 | 2023-07-03 | 도이체스크레브스포르슝스젠트룸스티프퉁데스외펜트리헨레크츠 | 표적 세포가 제한되는, 공동자극, 이중특이적 및 2가 항-cd28 항체 |
| KR20230148837A (ko) | 2021-02-25 | 2023-10-25 | 라이엘 이뮤노파마, 인크. | Ror1 표적화 키메라 항원 수용체 |
| WO2022180172A1 (en) | 2021-02-26 | 2022-09-01 | Bayer Aktiengesellschaft | Inhibitors of il-11 or il-11ra for use in the treatment of abnormal uterine bleeding |
| CN117222663A (zh) | 2021-03-03 | 2023-12-12 | 蜻蜓疗法股份有限公司 | 使用结合nkg2d、cd16和肿瘤相关抗原的多特异性结合蛋白治疗癌症的方法 |
| EP4305067A1 (en) | 2021-03-09 | 2024-01-17 | Xencor, Inc. | Heterodimeric antibodies that bind cd3 and cldn6 |
| US11859012B2 (en) | 2021-03-10 | 2024-01-02 | Xencor, Inc. | Heterodimeric antibodies that bind CD3 and GPC3 |
| US12016923B2 (en) | 2021-06-01 | 2024-06-25 | Triumvira Immunologics Usa, Inc. | Claudin 18.2 T cell-antigen couplers and uses thereof |
| US11453723B1 (en) | 2021-06-25 | 2022-09-27 | Mcmaster University | BCMA T cell-antigen couplers and uses thereof |
| WO2023164510A1 (en) | 2022-02-23 | 2023-08-31 | Xencor, Inc. | Anti-cd28 x anti-psma antibodies |
| EP4582106A1 (en) | 2022-08-29 | 2025-07-09 | Daiichi Sankyo Company, Limited | Antibody-drug conjugate including mutant fc region |
| WO2024170555A1 (en) | 2023-02-14 | 2024-08-22 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Il-15 fusion proteins with improved properties |
| EP4527851A1 (en) | 2023-09-22 | 2025-03-26 | Bayer Aktiengesellschaft | Bispecific antibodies binding ltbr and lrrc15 |
| WO2025147512A1 (en) * | 2024-01-02 | 2025-07-10 | Eli Lilly And Company | Immunogenicity assessment platform for biotherapeutic proteins |
| WO2025185760A1 (en) * | 2024-03-08 | 2025-09-12 | Itabmed Biopharmaceutical (Shanghai) Co., Ltd. | Multispecific antigen binding proteins and uses thereof |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9809951D0 (en) * | 1998-05-08 | 1998-07-08 | Univ Cambridge Tech | Binding molecules |
| WO2006031994A2 (en) | 2004-09-14 | 2006-03-23 | Xencor, Inc. | Monomeric immunoglobulin fc domains |
| EP1810980A1 (en) * | 2004-10-28 | 2007-07-25 | Osaka University | Interleukin-6 inhibitors |
| AU2006239851B2 (en) | 2005-04-26 | 2011-06-16 | Medimmune, Llc | Modulation of antibody effector function by hinge domain engineering |
| UA101142C2 (ru) * | 2006-03-17 | 2013-03-11 | Байоджэн Айдэк Ма Инк. | Способ разработки антитела |
| EA015992B1 (ru) * | 2006-03-17 | 2012-01-30 | Байоджен Айдек Эмэй Инк. | Стабилизированное антитело и многовалентная антигенсвязывающая молекула на его основе, способы получения и использования вышеназванного стабилизированного антитела |
| KR20100058509A (ko) * | 2007-07-31 | 2010-06-03 | 메디뮨 엘엘씨 | 다중특이적 에피토프 결합 단백질 및 이의 용도 |
| TWI464262B (zh) * | 2007-09-26 | 2014-12-11 | 中外製藥股份有限公司 | 抗體固定區的變異 |
| PL2310412T3 (pl) | 2008-06-20 | 2018-10-31 | Novartis Ag | Immunoglobuliny o zmniejszonej agregacji |
| EP2470568A2 (en) * | 2009-08-29 | 2012-07-04 | Abbott Laboratories | Therapeutic dll4 binding proteins |
| JP2013507926A (ja) * | 2009-10-14 | 2013-03-07 | メリマック ファーマシューティカルズ インコーポレーティッド | ＩＧＦ−１Ｒ及びＥｒｂＢ３シグナル伝達を標的とする二重特異的結合剤及びその使用 |
| EP2516468B1 (en) * | 2009-12-23 | 2016-03-02 | Synimmune GmbH | Anti-flt3 antibodies and methods of using the same |
| CA2855864A1 (en) * | 2011-11-17 | 2013-05-23 | Gundram Jung | Bi-specific antibodies for treating b-cell mediated autoimmune diseases or auto-reactive b-cells |
| DK2794658T3 (en) * | 2011-12-19 | 2017-06-19 | Synimmune Gmbh | BISPECIFIC ANTIBODY MOLECULE |
| EP2985294A1 (en) * | 2014-08-14 | 2016-02-17 | Deutsches Krebsforschungszentrum | Recombinant antibody molecule and its use for target cell restricted T cell activation |
| EP3192810A1 (en) * | 2016-01-14 | 2017-07-19 | Deutsches Krebsforschungszentrum | Psma binding antibody and uses thereof |
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2012
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- 2012-11-12 ES ES12798623.0T patent/ES2628075T3/es active Active
- 2012-11-12 EP EP12798623.0A patent/EP2794658B1/en active Active
- 2012-11-12 LT LTEP12798623.0T patent/LT2794658T/lt unknown
- 2012-11-12 CN CN201280070091.5A patent/CN104203981A/zh active Pending
- 2012-11-12 BR BR112014015018-4A patent/BR112014015018A2/pt not_active Application Discontinuation
- 2012-11-12 HR HRP20170658TT patent/HRP20170658T1/hr unknown
- 2012-11-12 US US14/366,669 patent/US9718893B2/en active Active
- 2012-11-12 CA CA2859767A patent/CA2859767C/en not_active Expired - Fee Related
- 2012-11-12 JP JP2014547791A patent/JP6441079B2/ja active Active
- 2012-11-12 WO PCT/EP2012/072364 patent/WO2013092001A1/en not_active Ceased
- 2012-11-12 SI SI201230939A patent/SI2794658T1/sl unknown
- 2012-11-12 HU HUE12798623A patent/HUE033245T2/hu unknown
- 2012-11-12 EA EA201400709A patent/EA201400709A1/ru unknown
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2017
- 2017-06-27 US US15/634,990 patent/US20180057608A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106999556A (zh) * | 2014-07-21 | 2017-08-01 | 武汉友芝友生物制药有限公司 | 细胞因子诱导的杀伤细胞的双特异性抗体介导的癌症治疗 |
Also Published As
| Publication number | Publication date |
|---|---|
| US9718893B2 (en) | 2017-08-01 |
| US20150119555A1 (en) | 2015-04-30 |
| EA201400709A1 (ru) | 2016-08-31 |
| LT2794658T (lt) | 2017-05-10 |
| BR112014015018A2 (pt) | 2020-10-27 |
| EP2794658B1 (en) | 2017-03-15 |
| EP2794658A1 (en) | 2014-10-29 |
| SI2794658T1 (sl) | 2017-05-31 |
| JP2015502373A (ja) | 2015-01-22 |
| ES2628075T3 (es) | 2017-08-01 |
| DK2794658T3 (en) | 2017-06-19 |
| JP6441079B2 (ja) | 2018-12-19 |
| HUE033245T2 (hu) | 2017-11-28 |
| HRP20170658T1 (hr) | 2017-06-30 |
| CN104203981A (zh) | 2014-12-10 |
| US20180057608A1 (en) | 2018-03-01 |
| CA2859767A1 (en) | 2013-06-27 |
| WO2013092001A1 (en) | 2013-06-27 |
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