JP7046903B2 - 可溶性線維芽細胞成長因子受容体３（ｓＦＧＦＲ３）ポリペプチドおよびその使用 - Google Patents
可溶性線維芽細胞成長因子受容体３（ｓＦＧＦＲ３）ポリペプチドおよびその使用 Download PDFInfo
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- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
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| EA201591324A1 (ru) | 2013-01-16 | 2016-01-29 | Инсерм (Энститю Насьональ Де Ля Сантэ Э Де Ля Решерш Медикаль) | Полипептид растворимого рецептора 3 фактора роста фибробластов (fgr3) для применения с целью предотвращения или лечения нарушений, связанных с замедлением роста скелета |
| RU2751483C2 (ru) | 2016-07-07 | 2021-07-14 | Пфайзер Инк. | Полипептиды, являющиеся растворимыми рецепторами 3 фактора роста фибробластов (sfgfr3), и пути их применения |
| CA3076396A1 (en) * | 2017-09-20 | 2019-03-28 | Pfizer Inc. | Treatment of abnormal visceral fat deposition using soluble fibroblast growth factor receptor 3 (sfgfr3) polypeptides |
| WO2020243478A1 (en) * | 2019-05-29 | 2020-12-03 | Massachusetts Eye And Ear Infirmary | Fibroblast growth factor 2 (fgf2) for treatment of human sensorineural hearing loss |
| US11625937B2 (en) * | 2020-04-06 | 2023-04-11 | Toyota Motor Engineering & Manufacturing North America, Inc. | Methods and systems for monitoring human body weight with vehicle sensors and big data AI analytics |
| WO2022106976A1 (en) | 2020-11-18 | 2022-05-27 | Pfizer Inc. | Stable pharmaceutical formulations of soluble fgfr3 decoys |
| WO2022254319A1 (en) | 2021-06-01 | 2022-12-08 | Pfizer Inc. | Cell culture method for producing sfgfr3 polypeptide |
| WO2024104922A1 (en) | 2022-11-14 | 2024-05-23 | Ascendis Pharma Growth Disorders A/S | Method of improving skeletal muscle function |
| WO2024194300A1 (en) | 2023-03-20 | 2024-09-26 | Ascendis Pharma Growth Disorders A/S | Method of treatment of a thoracolumbar deformity in a human subject with achondroplasia |
| CN116284327A (zh) * | 2023-03-28 | 2023-06-23 | 中国药科大学 | 一种靶向肿瘤的成纤维细胞生长因子19的重组蛋白及其应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011084711A2 (en) | 2009-12-17 | 2011-07-14 | Five Prime Therapeutics, Inc. | Hair growth methods using fgfr3 extracellular domains |
| JP2011529705A (ja) | 2008-08-04 | 2011-12-15 | ファイブ プライム セラピューティックス インコーポレイテッド | Ｆｇｆｒ細胞外ドメイン酸性領域突然変異タンパク質 |
| JP2016506912A (ja) | 2013-01-16 | 2016-03-07 | アンセルムＩｎｓｅｒｍ | 骨格成長遅延障害の予防または処置における使用のための、可溶性線維芽細胞増殖因子受容体３（ｆｇｒ３）ポリペプチド |
Family Cites Families (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8308236D0 (en) | 1983-03-25 | 1983-05-05 | Celltech Ltd | Dna vectors |
| DK0833620T3 (da) | 1995-06-12 | 2003-01-13 | Yeda Res & Dev | FGFR3, en markør for mesenkymale progenitorceller |
| US7067144B2 (en) | 1998-10-20 | 2006-06-27 | Omeros Corporation | Compositions and methods for systemic inhibition of cartilage degradation |
| US20040109850A1 (en) | 2000-12-18 | 2004-06-10 | Neelam Jaiswal | Treatment of bone disorders by modulation of fgfr3 |
| IL142118A0 (en) | 2001-03-20 | 2002-03-10 | Prochon Biotech Ltd | Method and composition for treatment of skeletal dysplasias |
| IL159177A0 (en) | 2001-06-20 | 2004-06-01 | Prochon Biotech Ltd | Antibodies that block receptor protein tyrosine kinase activation, methods of screening for and uses thereof |
| BRPI0203172B8 (pt) | 2001-09-28 | 2021-05-25 | Nakao Kazuwa | composição farmacêutica para acondroplasia |
| JP2003104908A (ja) | 2001-09-28 | 2003-04-09 | Ichikazu Nakao | 軟骨無形成症治療剤 |
| IL156495A0 (en) | 2003-06-17 | 2004-01-04 | Prochon Biotech Ltd | Use of fgfr3 antagonists for treating t cell mediated diseases |
| ATE533853T1 (de) | 2004-02-24 | 2011-12-15 | Allergan Inc | Botulinumtoxin-screening-assays |
| EP2083081A1 (en) | 2005-07-22 | 2009-07-29 | Five Prime Therapeutics, Inc. | Compositions and methods of treating disease with FGFR fusion proteins |
| CA2655504A1 (en) | 2006-06-15 | 2007-12-21 | Fibron Ltd. | Antibodies blocking fibroblast growth factor receptor activation and methods of use thereof |
| EP2083846B1 (en) | 2006-09-28 | 2015-07-15 | Hepacore Ltd. | N-terminal fgf variants having increased receptor selectivity and uses thereof |
| WO2008133873A2 (en) | 2007-04-25 | 2008-11-06 | Aveo Pharmaceuticals, Inc. | Fgf-binding fusion proteins |
| US8426396B2 (en) | 2008-01-08 | 2013-04-23 | Shriners Hospitals For Children | Treatment for achondroplasia |
| WO2010002862A2 (en) | 2008-07-01 | 2010-01-07 | Aveo Pharmaceuticals, Inc. | Fibroblast growth factor receptor 3 (fgfr3) binding proteins |
| TWI381848B (zh) | 2008-10-20 | 2013-01-11 | Imclone Llc | 抗纖維母細胞生長因子受體-3 (fgfr-3) 抗體及包含其之醫藥組合物 |
| AU2010229994B2 (en) | 2009-03-25 | 2016-08-18 | Genentech, Inc. | Anti-FGFR3 antibodies and methods using same |
| EP2478003A4 (en) | 2009-09-15 | 2013-05-29 | Five Prime Therapeutics Inc | HAIR GROWTH METHODS USING THE EXTRACELLULAR DOMAINS OF FGFR4 |
| US8614183B2 (en) | 2009-11-13 | 2013-12-24 | Five Prime Therapeutics, Inc. | Use of FGFR1 extra cellular domain proteins to treat cancers characterized by ligand-dependent activating mutations in FGFR2 |
| WO2011088196A2 (en) | 2010-01-14 | 2011-07-21 | Yale University | Inhibitors of receptor tyrosine kinases (rtk) and methods of use thereof |
| US8481038B2 (en) | 2010-11-15 | 2013-07-09 | Five Prime Therapeutics, Inc. | Treatment of cancer with elevated dosages of soluble FGFR1 fusion proteins |
| CA2823066A1 (en) | 2010-12-27 | 2012-07-05 | Alexion Pharma International Sarl | Compositions comprising natriuretic peptides and methods of use thereof |
| CN102219860B (zh) | 2011-05-20 | 2012-09-12 | 烟台荣昌生物工程有限公司 | FGFR-Fc融合蛋白及其用途 |
| EA030440B1 (ru) | 2011-10-24 | 2018-08-31 | Галозим, Инк. | Сопровождающая диагностика для терапии антигиалуронановым агентом и способы ее применения |
| FR2984325A1 (fr) | 2011-12-14 | 2013-06-21 | Sanofi Sa | Derives de pyrazolopyridine, leur procede de preparation et leur application en therapeutique |
| AU2013295805B2 (en) | 2012-07-24 | 2019-05-02 | The Trustees Of Columbia University In The City Of New York | Fusion proteins and methods thereof |
| KR20150037876A (ko) | 2012-07-27 | 2015-04-08 | 제넨테크, 인크. | Fgfr3 관련 상태의 치료 방법 |
| EP4223770A3 (en) | 2012-11-05 | 2023-10-18 | Foundation Medicine, Inc. | Novel fusion molecules and uses thereof |
| NZ722377A (en) | 2014-01-24 | 2022-09-30 | Ngm Biopharmaceuticals Inc | Binding proteins and methods of use thereof |
| EP3242888B8 (en) * | 2015-01-07 | 2021-06-02 | Pfizer Inc. | Soluble fgfr3 decoys for treating skeletal growth disorders |
| RU2751483C2 (ru) | 2016-07-07 | 2021-07-14 | Пфайзер Инк. | Полипептиды, являющиеся растворимыми рецепторами 3 фактора роста фибробластов (sfgfr3), и пути их применения |
| CA3076396A1 (en) | 2017-09-20 | 2019-03-28 | Pfizer Inc. | Treatment of abnormal visceral fat deposition using soluble fibroblast growth factor receptor 3 (sfgfr3) polypeptides |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011529705A (ja) | 2008-08-04 | 2011-12-15 | ファイブ プライム セラピューティックス インコーポレイテッド | Ｆｇｆｒ細胞外ドメイン酸性領域突然変異タンパク質 |
| WO2011084711A2 (en) | 2009-12-17 | 2011-07-14 | Five Prime Therapeutics, Inc. | Hair growth methods using fgfr3 extracellular domains |
| JP2016506912A (ja) | 2013-01-16 | 2016-03-07 | アンセルムＩｎｓｅｒｍ | 骨格成長遅延障害の予防または処置における使用のための、可溶性線維芽細胞増殖因子受容体３（ｆｇｒ３）ポリペプチド |
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