CA3031330C - Bispecific anti-her2 antibody - Google Patents
Bispecific anti-her2 antibody Download PDFInfo
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- CA3031330C CA3031330C CA3031330A CA3031330A CA3031330C CA 3031330 C CA3031330 C CA 3031330C CA 3031330 A CA3031330 A CA 3031330A CA 3031330 A CA3031330 A CA 3031330A CA 3031330 C CA3031330 C CA 3031330C
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- A61K39/39558—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against tumor tissues, cells, antigens
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Landscapes
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| CN201610584242.9A CN107446045A (zh) | 2016-07-22 | 2016-07-22 | 一种抗her2的抗体、其药物组合物及用途 |
| CN201610584242.9 | 2016-07-22 | ||
| US15/461,732 US9745382B1 (en) | 2016-07-22 | 2017-03-17 | Bispecific anti-HER2 antibody |
| US15/461,732 | 2017-03-17 | ||
| PCT/CN2017/093816 WO2018014864A1 (en) | 2016-07-22 | 2017-07-21 | Bispecific anti-her2 antibody |
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| CA3031330A1 CA3031330A1 (en) | 2018-01-25 |
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| WO2019094608A1 (en) | 2017-11-08 | 2019-05-16 | Denali Therapeutics Inc. | Anti-bace1 antibodies and methods of use thereof |
| CA3093477A1 (en) * | 2018-03-13 | 2019-09-19 | Zymeworks Inc. | Anti-her2 biparatopic antibody-drug conjugates and methods of use |
| WO2020000458A1 (zh) * | 2018-06-29 | 2020-01-02 | 深圳市博奥康生物科技有限公司 | 一种特异靶向人NGL基因的gRNA导向序列及其应用 |
| WO2020000452A1 (zh) * | 2018-06-29 | 2020-01-02 | 深圳市博奥康生物科技有限公司 | 一种靶向人NGL基因的新型RNAi干扰片段、RNAi载体及其制备方法和其应用 |
| AR115998A1 (es) * | 2018-08-22 | 2021-03-25 | Denali Therapeutics Inc | Polipéptidos anti-her2 y métodos de uso de los mismos |
| US20210188994A1 (en) * | 2018-08-29 | 2021-06-24 | United Biopharma Inc. | Afucosylated antibodies and manufacture thereof |
| WO2020156555A1 (zh) * | 2019-02-03 | 2020-08-06 | 苏州康聚生物科技有限公司 | 抗her2的双特异性抗体及其应用 |
| US20210238305A1 (en) * | 2019-03-01 | 2021-08-05 | Remegen Co., Ltd. | Antibody for her2 concomitant diagnosis immunohistochemical detection and application thereof |
| CN111848805B (zh) * | 2019-04-30 | 2023-05-05 | 非同（成都）生物科技有限公司 | 用于肿瘤免疫治疗的具有双Her2位点的双特异性抗体 |
| CN118955711A (zh) * | 2020-04-30 | 2024-11-15 | 正大天晴药业集团股份有限公司 | 靶向her2的抗原结合构建体及用途 |
| WO2021247718A1 (en) * | 2020-06-03 | 2021-12-09 | The Broad Institute, Inc. | Antagonistic biparatopic antibodies that specifically bind fibroblast growth factor receptor 2 and methods of using same |
| EP4190818A4 (en) * | 2020-07-28 | 2024-08-07 | Bio-Thera Solutions, Ltd. | ANTI-HER2 ANTIBODY AND ITS USE |
| CN114539413A (zh) * | 2020-11-25 | 2022-05-27 | 三生国健药业（上海）股份有限公司 | 结合her2的多价双特异性抗体、其制备方法和用途 |
| EP4386006A1 (en) * | 2021-07-05 | 2024-06-19 | Jiangsu Alphamab Biopharmaceuticals Co., Ltd. | Antibody-drug conjugate and application thereof |
| CN113817065B (zh) * | 2021-09-06 | 2023-04-18 | 深圳市乐土生物医药有限公司 | 一种抗her2的多肽及其用途 |
| CA3263784A1 (en) * | 2022-08-05 | 2024-02-08 | Janssen Biotech, Inc. | TRANSFERRIN RECEPTOR BINDING PROTEINS FOR THE TREATMENT OF BRAIN TUMORS |
| CN120051495A (zh) * | 2022-08-05 | 2025-05-27 | 詹森生物科技公司 | 用于治疗脑肿瘤的cd98结合构建体 |
| WO2024155891A2 (en) * | 2023-01-20 | 2024-07-25 | Washington University | Lilrb4/ilt3 antagonist compositions and methods of use thereof |
| WO2024183623A1 (zh) * | 2023-03-03 | 2024-09-12 | 盛禾(中国)生物制药有限公司 | 一种抗her2抗体在制备治疗癌症的药物中的用途 |
| WO2024183622A1 (zh) * | 2023-03-03 | 2024-09-12 | 盛禾(中国)生物制药有限公司 | 一种抗her2抗体在制备治疗癌症的药物中的用途 |
| WO2025124463A1 (zh) * | 2023-12-12 | 2025-06-19 | 上海宝济药业股份有限公司 | 抗her2的双特异性抗体及其应用 |
| CN118206662A (zh) * | 2024-05-14 | 2024-06-18 | 中国人民解放军军事科学院军事医学研究院 | 一种靶向Her2的新型单克隆抗体及其应用 |
| CN119462959B (zh) * | 2024-10-24 | 2025-12-19 | 南京元迈细胞生物科技有限公司 | 嵌合抗原受体及其修饰的细胞 |
Family Cites Families (10)
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| WO1989006692A1 (en) | 1988-01-12 | 1989-07-27 | Genentech, Inc. | Method of treating tumor cells by inhibiting growth factor receptor function |
| AU675916B2 (en) | 1991-06-14 | 1997-02-27 | Genentech Inc. | Method for making humanized antibodies |
| DK2263691T3 (da) | 2002-07-15 | 2012-10-22 | Hoffmann La Roche | Behandling af cancer med det rekombinante humaniserede monoklonale anti-ErbB2-antistof 2C4 (rhuMAb-2C4) |
| RU2015141529A (ru) * | 2013-04-05 | 2017-05-15 | Дженентек, Инк. | Антитела и биспецифические антитела к il-4 и их применение |
| JP6817064B2 (ja) * | 2013-11-27 | 2021-01-20 | ザイムワークス，インコーポレイテッド | Ｈｅｒ２を標的とする二重特異性抗原結合性コンストラクト |
| EP3327038B1 (en) | 2013-12-20 | 2020-09-23 | F. Hoffmann-La Roche AG | Bispecific her2 antibodies and methods of use |
| JP2017512765A (ja) * | 2014-04-11 | 2017-05-25 | メディミューン，エルエルシー | 二重特異性ｈｅｒ２抗体 |
| CN105017421B (zh) | 2014-04-16 | 2017-12-26 | 中国人民解放军海军总医院 | 一种抗her2双特异性抗体及其制备方法与应用 |
| RU2725093C2 (ru) * | 2014-04-25 | 2020-06-29 | Дженентек, Инк. | Способы лечения раннего рака молочной железы трастузумабом-mcc-dm1 и пертузумабом |
| CN110658340B (zh) * | 2015-01-08 | 2023-10-31 | 苏州康宁杰瑞生物科技有限公司 | 具有共同轻链的双特异性抗体或抗体混合物 |
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| CN107446045A (zh) | 2017-12-08 |
| US9745382B1 (en) | 2017-08-29 |
| EP3487888A1 (en) | 2019-05-29 |
| CN109715671B (zh) | 2020-08-21 |
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