CN114127106A - 人源化抗VEGF Fab抗体片段及其用途 - Google Patents
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Abstract
本发明属于肿瘤免疫治疗领域，涉及人源化抗VEGF Fab抗体片段。本发明公开编码所述抗体片段的核酸序列(包括重/轻链可变区)、含有所述核酸序列的载体、药物组合物和试剂盒。本发明公开的抗VEGF Fab抗体片段可以以高亲和力特异性结合VEGF，阻断VEGF与受体VEGFR2结合，还能中和VEGF对HUVEC细胞的增殖作用。相比于全长结构，Fab片段的抗体具有更强的穿透性，和更低的胃肠道穿孔、高血压和出血等毒副作用且不能激发补体级联反应，从而降低引发眼内炎和自身免疫炎症反应的风险，可用于临床治疗多种以脉络膜新生血管为特征的眼病，包括但不局限于年龄相关性老年黄斑变性(AMD)、糖尿病性黄斑水肿(DME)、视网膜水肿、退行性近视、脉络膜新生血管(CNV)。
Description
PCT国内申请，说明书已公开。
Claims (25)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2019106573118 | 2019-07-19 | ||
| CN201910657311 | 2019-07-19 | ||
| PCT/CN2020/102560 WO2021013065A1 (zh) | 2019-07-19 | 2020-07-17 | 人源化抗VEGF Fab抗体片段及其用途 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114127106A true CN114127106A (zh) | 2022-03-01 |
| CN114127106B CN114127106B (zh) | 2024-01-12 |
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| CN202080051385.8A Active CN114127106B (zh) | 2019-07-19 | 2020-07-17 | 人源化抗VEGF Fab抗体片段及其用途 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20220135665A1 (zh) |
| EP (1) | EP4043490A4 (zh) |
| JP (1) | JP7229419B2 (zh) |
| KR (1) | KR20220034868A (zh) |
| CN (1) | CN114127106B (zh) |
| AU (1) | AU2020316495A1 (zh) |
| BR (1) | BR112022001021A2 (zh) |
| CA (1) | CA3150046C (zh) |
| MX (1) | MX2022000780A (zh) |
| WO (1) | WO2021013065A1 (zh) |
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| KR20220071177A (ko) * | 2019-07-19 | 2022-05-31 | 사이노셀테크 엘티디. | 인간화 항-vegf 단클론 항체 |
| CN116568542A (zh) | 2020-12-18 | 2023-08-08 | 日产自动车株式会社 | 内燃机的催化剂暖机控制方法以及催化剂暖机控制装置 |
| WO2024055996A1 (zh) * | 2022-09-14 | 2024-03-21 | 寻济生物科技（北京）有限公司 | 一种抗vegfa抗体或其抗原结合片段及其应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104761643A (zh) * | 2003-08-01 | 2015-07-08 | 健泰科生物技术公司 | 抗-vegf抗体 |
| CN107108727A (zh) * | 2014-05-01 | 2017-08-29 | 科学和技术研究全国委员会（科尼特） | 对人vegf‑a有异常强的结合亲和力并具有与人vegf‑b的交叉反应性的抗人vegf抗体 |
| CN108137681A (zh) * | 2015-09-23 | 2018-06-08 | 豪夫迈·罗氏有限公司 | 抗-vegf抗体的优化的变体 |
| US20190202904A1 (en) * | 2016-09-07 | 2019-07-04 | University Of Toronto | Synthetic antibodies against vegf and their uses |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5179017A (en) | 1980-02-25 | 1993-01-12 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4634665A (en) | 1980-02-25 | 1987-01-06 | The Trustees Of Columbia University In The City Of New York | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4399216A (en) | 1980-02-25 | 1983-08-16 | The Trustees Of Columbia University | Processes for inserting DNA into eucaryotic cells and for producing proteinaceous materials |
| US4510245A (en) | 1982-11-18 | 1985-04-09 | Chiron Corporation | Adenovirus promoter system |
| GB8308235D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Polypeptides |
| US5168062A (en) | 1985-01-30 | 1992-12-01 | University Of Iowa Research Foundation | Transfer vectors and microorganisms containing human cytomegalovirus immediate-early promoter-regulatory DNA sequence |
| US4968615A (en) | 1985-12-18 | 1990-11-06 | Ciba-Geigy Corporation | Deoxyribonucleic acid segment from a virus |
| IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
| DK0590058T3 (da) | 1991-06-14 | 2004-03-29 | Genentech Inc | Humaniseret heregulin-antistof |
| IL138608A0 (en) | 1998-04-02 | 2001-10-31 | Genentech Inc | Antibody variants and fragments thereof |
| US6194551B1 (en) | 1998-04-02 | 2001-02-27 | Genentech, Inc. | Polypeptide variants |
| US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
| US7667004B2 (en) * | 2001-04-17 | 2010-02-23 | Abmaxis, Inc. | Humanized antibodies against vascular endothelial growth factor |
| CN102286101B (zh) * | 2011-08-08 | 2013-05-08 | 常州亚当生物技术有限公司 | 抗VEGF单克隆抗体Fab片段Vasculizumab及其应用 |
| US11007259B2 (en) * | 2016-01-06 | 2021-05-18 | Order-Made Medical Research Inc. | High-affinity anti-VEGF antibody |
-
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104761643A (zh) * | 2003-08-01 | 2015-07-08 | 健泰科生物技术公司 | 抗-vegf抗体 |
| CN107108727A (zh) * | 2014-05-01 | 2017-08-29 | 科学和技术研究全国委员会（科尼特） | 对人vegf‑a有异常强的结合亲和力并具有与人vegf‑b的交叉反应性的抗人vegf抗体 |
| CN108137681A (zh) * | 2015-09-23 | 2018-06-08 | 豪夫迈·罗氏有限公司 | 抗-vegf抗体的优化的变体 |
| US20190202904A1 (en) * | 2016-09-07 | 2019-07-04 | University Of Toronto | Synthetic antibodies against vegf and their uses |
Non-Patent Citations (2)
| Title |
|---|
| SHARON D SOLOMON, ET AL.: "Anti-vascular endothelial growth factor for neovascular age-related macular degeneration", COCHRANE DATABASE SYST REV ., vol. 3, no. 3, pages 28 - 30 * |
| 肖博;王红燕;: "抗VEGF治疗眼底病变的研究进展", 继续医学教育, no. 08, pages 154 - 156 * |
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| AU2020316495A1 (en) | 2022-02-03 |
| US20220135665A1 (en) | 2022-05-05 |
| JP2022537072A (ja) | 2022-08-23 |
| WO2021013065A1 (zh) | 2021-01-28 |
| MX2022000780A (es) | 2022-02-14 |
| EP4043490A4 (en) | 2023-08-16 |
| CA3150046A1 (en) | 2021-01-28 |
| BR112022001021A2 (pt) | 2022-04-12 |
| JP7229419B2 (ja) | 2023-02-27 |
| KR20220034868A (ko) | 2022-03-18 |
| CA3150046C (en) | 2023-11-14 |
| CN114127106B (zh) | 2024-01-12 |
| EP4043490A1 (en) | 2022-08-17 |
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