CA3066555A1 - Cd38 modulating antibody - Google Patents
Cd38 modulating antibody Download PDFInfo
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- CA3066555A1 CA3066555A1 CA3066555A CA3066555A CA3066555A1 CA 3066555 A1 CA3066555 A1 CA 3066555A1 CA 3066555 A CA3066555 A CA 3066555A CA 3066555 A CA3066555 A CA 3066555A CA 3066555 A1 CA3066555 A1 CA 3066555A1
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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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Applications Claiming Priority (25)
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| US201762517149P | 2017-06-08 | 2017-06-08 | |
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| US201762517745P | 2017-06-09 | 2017-06-09 | |
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| US201762582676P | 2017-11-07 | 2017-11-07 | |
| US201762582653P | 2017-11-07 | 2017-11-07 | |
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| PCT/EP2018/065243 WO2018224685A1 (en) | 2017-06-08 | 2018-06-08 | Cd38 modulating antibody |
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| CN111032693B (zh) | 2017-08-16 | 2023-09-26 | 黑带医疗有限公司 | Cd38调节抗体 |
| CN110144008B (zh) * | 2018-02-12 | 2021-03-19 | 杭州尚健生物技术有限公司 | Cd38蛋白抗体及其应用 |
| KR20210114963A (ko) | 2019-01-11 | 2021-09-24 | 오메로스 코포레이션 | 암을 치료하기 위한 방법 및 조성물 |
| AU2020211728A1 (en) | 2019-01-23 | 2021-08-12 | Encefa | CD31 competitors and uses thereof |
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| CN113874397A (zh) | 2019-03-29 | 2021-12-31 | 艾库斯生物科学有限公司 | 利用鉴定的腺苷指纹治疗癌症 |
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| CN114457028A (zh) * | 2020-10-30 | 2022-05-10 | 未来智人再生医学研究院(广州)有限公司 | 一种表达cd38抗体的多能干细胞及其衍生物与应用 |
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| US8877688B2 (en) | 2007-09-14 | 2014-11-04 | Adimab, Llc | Rationally designed, synthetic antibody libraries and uses therefor |
| CA2697193C (en) | 2007-09-14 | 2017-06-06 | Adimab, Inc. | Rationally designed, synthetic antibody libraries and uses therefor |
| DK2342220T3 (da) | 2008-10-06 | 2021-08-09 | Univ British Columbia | Metoder og systemer til forudsigelse af misfoldede proteinepitoper |
| CA2773240C (en) | 2009-09-22 | 2015-11-10 | Volker Sandig | Process for producing molecules containing specialized glycan structures |
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| JOP20210044A1 (ar) | 2010-12-30 | 2017-06-16 | Takeda Pharmaceuticals Co | الأجسام المضادة لـ cd38 |
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| BR112015021521A2 (pt) | 2013-03-15 | 2017-10-10 | Genentech Inc | anticorpos anti-crth2 e métodos para seu uso |
| US10675352B2 (en) | 2014-02-14 | 2020-06-09 | Centrose, Llc | Extracellular targeted drug conjugates |
| TN2017000532A1 (en) | 2014-03-28 | 2019-04-12 | Xencor Inc | Bispecific antibodies that bind to cd38 and cd3. |
| MA40894A (fr) | 2014-11-04 | 2017-09-12 | Glenmark Pharmaceuticals Sa | Immunoglobulines hétéro-dimères reciblant des lymphocytes t cd3/cd38 et leurs procédés de production |
| AU2015355126B9 (en) | 2014-12-01 | 2020-03-26 | Inovio Pharmaceuticals, Inc. | DNA antibody constructs and method of using same |
| US10059774B2 (en) | 2015-04-08 | 2018-08-28 | Sorrento Therapeutics, Inc. | Antibody therapeutics that bind CD38 |
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| FI3313441T3 (fi) | 2015-06-24 | 2024-03-28 | Janssen Biotech Inc | Kiinteiden kasvainten immunomodulaatio ja hoito spesifisesti cd38:aa sitovilla vasta-aineilla |
| US10358497B2 (en) | 2015-09-29 | 2019-07-23 | Amgen Inc. | Methods of treating cardiovascular disease with an ASGR inhibitor |
| CN115594765A (zh) | 2015-10-02 | 2023-01-13 | 豪夫迈·罗氏有限公司（Ch） | 对共刺激性tnf受体特异性的双特异性抗体 |
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