CN118085103A - 用于治疗疼痛的化合物和方法 - Google Patents
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| CN201580017113.5A CN106459190A (zh) | 2014-02-02 | 2015-02-02 | 用于治疗疼痛的化合物和方法 |
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| EP3696193A1 (en) * | 2014-02-02 | 2020-08-19 | MedImmune Limited | Chimeric protein composed of ngf antagonist domain and a tnfa antagonist domain |
| US9862760B2 (en) * | 2015-09-16 | 2018-01-09 | Novartis Ag | Polyomavirus neutralizing antibodies |
| CN111132997A (zh) | 2017-09-21 | 2020-05-08 | 默克专利有限公司 | 包含fgf-18部分的融合蛋白 |
| WO2021142573A1 (zh) * | 2020-01-13 | 2021-07-22 | 丁邦 | 一种融合蛋白及其制法和用途 |
| KR20230084199A (ko) * | 2020-09-28 | 2023-06-12 | 메디뮨 리미티드 | 통증 치료를 위한 화합물 및 방법 |
| CN114574444B (zh) * | 2020-12-01 | 2024-05-03 | 达达生物技术(北京)有限公司 | 自体纤维母细胞在制备抗类风湿关节炎药物中的应用 |
| TWI821881B (zh) * | 2021-01-29 | 2023-11-11 | 醫研生物科技有限公司 | 腫瘤壞死因子α重組抗體及其用途 |
| CN116179667A (zh) * | 2022-09-21 | 2023-05-30 | 福建中妆技术研究有限公司 | 基于斑马鱼模型中trpv1信号通路筛选皮肤疼痛舒缓原料的试剂盒及应用 |
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| EP1846451B1 (en) * | 2005-01-24 | 2013-05-15 | Medimmune Limited | Human antibodies against human ngf |
| MX380352B (es) * | 2006-06-12 | 2025-03-12 | Aptevo Res & Development Llc | Proteinas de union multivalentes monocatenarias con funcion efectora. |
| GB0624500D0 (en) * | 2006-12-07 | 2007-01-17 | Istituto Superiore Di Sanito | A novel passive vaccine for candida infections |
| US7691980B2 (en) | 2007-01-09 | 2010-04-06 | Bio-Rad Laboratories, Inc. | Enhanced capacity and purification of antibodies by mixed mode chromatography in the presence of aqueous-soluble nonionic organic polymers |
| KR20100021601A (ko) * | 2007-05-14 | 2010-02-25 | 바이오겐 아이덱 엠에이 인코포레이티드 | 단일-쇄 Ｆｃ(ＳｃＦｃ) 부분, 이를 포함하는 결합 폴리펩타이드, 및 이에 관련된 방법 |
| WO2009092014A1 (en) | 2008-01-18 | 2009-07-23 | Gagnon Peter S | Enhanced purification of antibodies and antibody fragments by apatite chromatography |
| BRPI0913406A2 (pt) | 2008-06-03 | 2018-01-09 | Abbott Lab | imunoglobulinas de domínio variável duplo e usos das mesmas |
| US8822645B2 (en) * | 2008-07-08 | 2014-09-02 | Abbvie Inc. | Prostaglandin E2 dual variable domain immunoglobulins and uses thereof |
| JP2011016676A (ja) * | 2009-07-07 | 2011-01-27 | Sumitomo Electric Ind Ltd | 窒化物半導体基板の製造方法 |
| US8716450B2 (en) * | 2009-10-15 | 2014-05-06 | Abbvie Inc. | Dual variable domain immunoglobulins and uses thereof |
| CA2782320A1 (en) | 2009-12-02 | 2011-06-09 | Acceleron Pharma Inc. | Compositions and methods for increasing serum half-life of fc fusion proteins |
| KR20130010123A (ko) * | 2010-04-07 | 2013-01-25 | 아비에 인코포레이티드 | ＴＮＦ-α 결합 단백질 |
| DK2714738T3 (en) * | 2011-05-24 | 2019-01-28 | Zyngenia Inc | MULTIVALENT AND MONOVALENT MULTISPECIFIC COMPLEXES AND THEIR APPLICATIONS |
| EP2776061B1 (en) | 2011-11-07 | 2019-08-14 | MedImmune, LLC | Multispecific and multivalent binding proteins and uses thereof |
| TW201333033A (zh) | 2011-12-30 | 2013-08-16 | Abbvie Inc | 雙可變域免疫球蛋白及其用途 |
| WO2014106001A2 (en) * | 2012-12-28 | 2014-07-03 | Abbvie, Inc. | Dual specific binding proteins having a receptor sequence |
| TW201446800A (zh) | 2013-03-15 | 2014-12-16 | Abbvie Inc | 針對ＴＮＦα之雙特異性結合蛋白 |
| EP3696193A1 (en) | 2014-02-02 | 2020-08-19 | MedImmune Limited | Chimeric protein composed of ngf antagonist domain and a tnfa antagonist domain |
| CA2874083C (en) * | 2014-12-05 | 2024-01-02 | Universite Laval | Tdp-43-binding polypeptides useful for the treatment of neurodegenerative diseases |
| US20210009671A1 (en) | 2019-05-10 | 2021-01-14 | Medimmune Limited | Compounds and methods for treating pain |
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