CN109071678A - 神经生长因子融合蛋白、制备方法及其用途 - Google Patents
神经生长因子融合蛋白、制备方法及其用途 Download PDFInfo
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- CN109071678A CN109071678A CN201780017018.4A CN201780017018A CN109071678A CN 109071678 A CN109071678 A CN 109071678A CN 201780017018 A CN201780017018 A CN 201780017018A CN 109071678 A CN109071678 A CN 109071678A
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
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- C07K2319/00—Fusion polypeptide
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Abstract
神经生长因子融合蛋白、制备方法及其用途，属于生物制药领域。一种神经生长因子融合蛋白，通式为A‑B或A‑L‑B；其中A为神经生长因子，L为连接肽，B为IgG的Fc部分、或IgG的Fc部分的类似物、或IgG的Fc部分的片段。优点是：所述的神经生长因子融合蛋白具有比野生型NGF更高的生物活性，半衰期可延长17倍以上，大大减少了用药频率，药效得到了明显提高。
Description
PCT国内申请，说明书已公开。
Claims (21)
- PCT国内申请，权利要求书已公开。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610159303 | 2016-03-18 | ||
| CN2016101593037 | 2016-03-18 | ||
| PCT/CN2017/077025 WO2017157325A1 (zh) | 2016-03-18 | 2017-03-17 | 神经生长因子融合蛋白、制备方法及其用途 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109071678A true CN109071678A (zh) | 2018-12-21 |
| CN109071678B CN109071678B (zh) | 2022-05-20 |
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| CN201780017019.9A Active CN109153709B (zh) | 2016-03-18 | 2017-03-17 | 神经生长因子突变体 |
| CN202210214938.8A Active CN114671941B (zh) | 2016-03-18 | 2017-03-17 | 神经生长因子突变体 |
| CN201780017018.4A Active CN109071678B (zh) | 2016-03-18 | 2017-03-17 | 神经生长因子融合蛋白、制备方法及其用途 |
| CN202210214942.4A Withdrawn CN114671942A (zh) | 2016-03-18 | 2017-03-17 | 神经生长因子突变体 |
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| CN202210214934.XA Active CN114671940B (zh) | 2016-03-18 | 2017-03-17 | 神经生长因子突变体 |
| CN201780017019.9A Active CN109153709B (zh) | 2016-03-18 | 2017-03-17 | 神经生长因子突变体 |
| CN202210214938.8A Active CN114671941B (zh) | 2016-03-18 | 2017-03-17 | 神经生长因子突变体 |
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| CN202210214942.4A Withdrawn CN114671942A (zh) | 2016-03-18 | 2017-03-17 | 神经生长因子突变体 |
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| EP (3) | EP3431507B1 (zh) |
| CN (5) | CN114671940B (zh) |
| DK (1) | DK3431507T3 (zh) |
| ES (1) | ES2966133T3 (zh) |
| HU (1) | HUE064504T2 (zh) |
| WO (2) | WO2017157326A1 (zh) |
Families Citing this family (7)
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|---|---|---|---|---|
| HUE064504T2 (hu) | 2016-03-18 | 2024-03-28 | Staidson Beijing Biopharmaceuticals Co Ltd | Idegi növekedési faktort tartalmazó fúziós fehérje, valamint elõállítási eljárása és alkalmazása |
| CN113845583B (zh) * | 2020-06-28 | 2023-08-11 | 江苏中新医药有限公司 | 一种修饰的重组人神经生长因子及其制备方法 |
| WO2022105847A1 (en) | 2020-11-19 | 2022-05-27 | Staidson (Beijing) Biopharmaceuticals Co. , Ltd. | Long-acting nerve growth factor polypeptides and uses thereof |
| CN115894705A (zh) * | 2021-09-30 | 2023-04-04 | 三生国健药业（上海）股份有限公司 | 一种β-NGF融合蛋白、其制备方法及用途 |
| WO2023088351A1 (zh) * | 2021-11-19 | 2023-05-25 | 舒泰神（北京）生物制药股份有限公司 | 神经生长因子在制备用于治疗或改善生殖系统疾病的药物中的用途 |
| EP4342485A1 (en) * | 2022-09-23 | 2024-03-27 | Dompe' Farmaceutici S.P.A. | Ngf for the treatment of spasticity |
| CN115813951B (zh) * | 2022-11-10 | 2023-07-21 | 北京昱龙盛世生物科技有限公司 | 转基因干细胞及其用于治疗失眠症或睡眠障碍的用途 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1698883A (zh) * | 2004-05-21 | 2005-11-23 | 舒泰神（北京）药业有限公司 | 神经生长因子在制备有效减轻体重的药物中的应用 |
| US20090137471A1 (en) * | 1997-04-29 | 2009-05-28 | Presta Leonard G | Ngf variants |
| CN102665759A (zh) * | 2009-11-19 | 2012-09-12 | 默克雪兰诺有限公司 | 人源化抗il-22ra抗体 |
| CN105273087A (zh) * | 2014-07-14 | 2016-01-27 | 复旦大学 | NGF-Fc融合蛋白及其制备方法 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5349055A (en) | 1992-03-06 | 1994-09-20 | Persson Hakan B | Nerve growth factor having altered receptor binding specificities |
| US5728803A (en) | 1994-06-03 | 1998-03-17 | Genentech, Inc. | Pantropic neurotrophic factors |
| EP1689865A2 (en) * | 2003-10-23 | 2006-08-16 | Monika Holmberg | A novel mutated nerve growth factor beta gene, proteins encoded thereby, and products and methods related thereto |
| ATE409741T1 (de) * | 2004-01-19 | 2008-10-15 | Nsgene As | Nervenwachstumsfaktor sezernierende menschliche therapeutische zellen |
| ITRM20060367A1 (it) * | 2006-07-13 | 2008-01-14 | Lay Line Genomics Spa | Muteine del hngf usi terapeutici e composizioni farmaceutiche |
| CN101260398B (zh) * | 2007-03-07 | 2013-06-05 | 舒泰神（北京）生物制药股份有限公司 | 神经生长因子基因定位改造动物及其制备方法和应用 |
| EP2231179A2 (en) | 2007-12-20 | 2010-09-29 | Cytos Biotechnology AG | Ngf conjugates and uses thereof |
| WO2012075340A2 (en) * | 2010-12-01 | 2012-06-07 | Alderbio Holdings Llc | Anti-ngf compositions and use thereof |
| CN102898514B (zh) * | 2011-07-28 | 2015-04-29 | 中国人民解放军军事医学科学院生物工程研究所 | 重组人神经生长因子缺失突变体及其制备方法和用途 |
| CN103159843B (zh) | 2011-12-19 | 2014-11-05 | 中国科学院生物物理研究所 | 具有低免疫副作用的神经生长因子突变体的制备方法及其药物应用价值 |
| CN103376248B (zh) | 2012-04-26 | 2016-06-01 | 舒泰神（北京）生物制药股份有限公司 | 神经生长因子活性定量测定方法 |
| HUE064504T2 (hu) | 2016-03-18 | 2024-03-28 | Staidson Beijing Biopharmaceuticals Co Ltd | Idegi növekedési faktort tartalmazó fúziós fehérje, valamint elõállítási eljárása és alkalmazása |
-
2017
- 2017-03-17 HU HUE17765867A patent/HUE064504T2/hu unknown
- 2017-03-17 WO PCT/CN2017/077038 patent/WO2017157326A1/zh active Application Filing
- 2017-03-17 CN CN202210214934.XA patent/CN114671940B/zh active Active
- 2017-03-17 US US16/085,984 patent/US11883464B2/en active Active
- 2017-03-17 CN CN201780017019.9A patent/CN109153709B/zh active Active
- 2017-03-17 CN CN202210214938.8A patent/CN114671941B/zh active Active
- 2017-03-17 US US16/085,977 patent/US11213568B2/en active Active
- 2017-03-17 EP EP17765867.1A patent/EP3431507B1/en active Active
- 2017-03-17 DK DK17765867.1T patent/DK3431507T3/da active
- 2017-03-17 CN CN201780017018.4A patent/CN109071678B/zh active Active
- 2017-03-17 WO PCT/CN2017/077025 patent/WO2017157325A1/zh active Application Filing
- 2017-03-17 EP EP23203486.8A patent/EP4292649A3/en active Pending
- 2017-03-17 ES ES17765867T patent/ES2966133T3/es active Active
- 2017-03-17 EP EP17765868.9A patent/EP3431494B1/en active Active
- 2017-03-17 CN CN202210214942.4A patent/CN114671942A/zh not_active Withdrawn
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2021
- 2021-11-19 US US17/455,870 patent/US20220088136A1/en not_active Abandoned
-
2023
- 2023-02-07 US US18/165,801 patent/US20230241169A1/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090137471A1 (en) * | 1997-04-29 | 2009-05-28 | Presta Leonard G | Ngf variants |
| CN1698883A (zh) * | 2004-05-21 | 2005-11-23 | 舒泰神（北京）药业有限公司 | 神经生长因子在制备有效减轻体重的药物中的应用 |
| CN102665759A (zh) * | 2009-11-19 | 2012-09-12 | 默克雪兰诺有限公司 | 人源化抗il-22ra抗体 |
| CN105273087A (zh) * | 2014-07-14 | 2016-01-27 | 复旦大学 | NGF-Fc融合蛋白及其制备方法 |
Non-Patent Citations (1)
| Title |
|---|
| NIRANJANA,K.R.P.等: "GenBank：AEV43323.1", 《GENBANK》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| HUE064504T2 (hu) | 2024-03-28 |
| CN109153709B (zh) | 2022-05-27 |
| US20200331977A1 (en) | 2020-10-22 |
| US11883464B2 (en) | 2024-01-30 |
| ES2966133T3 (es) | 2024-04-18 |
| WO2017157325A1 (zh) | 2017-09-21 |
| CN114671940A (zh) | 2022-06-28 |
| DK3431507T3 (da) | 2024-01-02 |
| CN114671940B (zh) | 2023-09-26 |
| EP3431507B1 (en) | 2023-11-22 |
| EP4292649A3 (en) | 2024-02-21 |
| US20190105373A1 (en) | 2019-04-11 |
| US20220088136A1 (en) | 2022-03-24 |
| CN114671941A (zh) | 2022-06-28 |
| WO2017157326A1 (zh) | 2017-09-21 |
| EP3431507A4 (en) | 2019-08-14 |
| CN114671941B (zh) | 2023-09-26 |
| EP3431507A1 (en) | 2019-01-23 |
| EP4292649A2 (en) | 2023-12-20 |
| CN109071678B (zh) | 2022-05-20 |
| EP3431494B1 (en) | 2024-05-01 |
| CN109153709A (zh) | 2019-01-04 |
| US20230241169A1 (en) | 2023-08-03 |
| CN114671942A (zh) | 2022-06-28 |
| EP3431494A4 (en) | 2020-01-01 |
| US11213568B2 (en) | 2022-01-04 |
| EP3431494A1 (en) | 2019-01-23 |
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