JP5577345B2 - 線維芽細胞成長因子受容体３（ｆｇｆｒ−３）阻害剤および治療方法 - Google Patents
線維芽細胞成長因子受容体３（ｆｇｆｒ−３）阻害剤および治療方法 Download PDFInfo
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| MX2015011428A (es) | 2013-03-06 | 2016-02-03 | Genentech Inc | Metodos para tratar y prevenir la resistencia a los farmacos para el cancer. |
| TWI541022B (zh) | 2013-12-18 | 2016-07-11 | 應克隆公司 | 針對纖維母細胞生長因子受體－３（ｆｇｆｒ３）之化合物及治療方法 |
| EP3122776B1 (en) | 2014-03-25 | 2021-04-28 | Regeneron Pharmaceuticals, Inc. | Fgf21 receptor agonists and uses thereof |
| EP3151857A4 (en) * | 2014-06-03 | 2018-04-18 | Merck Sharp & Dohme Corp. | Anti-blys antibodies |
| CN107073121A (zh) | 2014-06-13 | 2017-08-18 | 基因泰克公司 | 治疗及预防癌症药物抗性的方法 |
| MX384149B (es) * | 2014-09-05 | 2025-03-14 | Hyperfine Inc | Aumento ferromagnético para formación de imagenes por resonancia magnética. |
| KR102470456B1 (ko) | 2014-09-26 | 2022-11-23 | 얀센 파마슈티카 엔.브이. | Fgfr 억제제를 사용한 치료에 반응할 암 환자를 확인하는 데 있어서 fgfr 돌연변이 유전자 패널의 사용 |
| SG11201706727XA (en) * | 2015-02-19 | 2017-09-28 | Bioclin Therapeutics Inc | Methods, compositions, and kits for treatment of cancer |
| US20180237424A1 (en) | 2015-03-03 | 2018-08-23 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Fgfr3 antagonists |
| TW201711702A (zh) | 2015-06-04 | 2017-04-01 | 應克隆公司 | 使用針對纖維母細胞生長因子受體３（ｆｇｆｒ３）之化合物的療法 |
| WO2017100642A1 (en) | 2015-12-11 | 2017-06-15 | Regeneron Pharmaceuticals, Inc. | Methods for reducing or preventing growth of tumors resistant to egfr and/or erbb3 blockade |
| MX2018016257A (es) | 2016-07-07 | 2019-11-21 | Therachon Sas | Polipéptidos del receptor 3 del factor de crecimiento de fibroblastos solubles (sfgfr3) y usos de los mismos. |
| US20180244785A1 (en) * | 2017-01-09 | 2018-08-30 | Merrimack Pharmaceuticals, Inc. | Anti-fgfr antibodies and methods of use |
| AR123306A1 (es) | 2020-08-21 | 2022-11-16 | Genzyme Corp | Anticuerpos fgfr3 y métodos de uso |
| CN114015770B (zh) * | 2021-12-30 | 2022-04-26 | 佛山市第三人民医院(佛山市精神卫生中心) | 精神分裂全外周血rna标志物fgfr3及其应用 |
| US20240173426A1 (en) * | 2022-11-14 | 2024-05-30 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for fibroblast growth factor receptor 3-mediated delivery to astrocytes |
| IL322053A (en) | 2023-01-13 | 2025-09-01 | Regeneron Pharma | FGFR3 binding molecules and methods of using them |
| WO2025240335A1 (en) | 2024-05-13 | 2025-11-20 | Regeneron Pharmaceuticals, Inc. | Fgfr3 binding molecules and methods of use thereof |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| AU612370B2 (en) | 1987-05-21 | 1991-07-11 | Micromet Ag | Targeted multifunctional proteins |
| JP2005500034A (ja) | 2001-06-20 | 2005-01-06 | プロション バイオテク リミテッド | 受容体型タンパク質チロシンキナーゼ活性化を遮断する抗体、そのスクリーニング方法、及びその使用 |
| CA2550245A1 (en) | 2003-12-19 | 2005-07-21 | Five Prime Therapeutics, Inc. | Fibroblast growth factor receptors 1, 2, 3, and 4 as targets for therapeutic intervention |
| MX2008014978A (es) * | 2006-06-06 | 2008-12-09 | Crucell Holland Bv | Moleculas de union humanas que tienen actividad exterminadora contra enterococos y staphylococcus aureus y usos de las mismas. |
| US8192927B2 (en) * | 2006-09-07 | 2012-06-05 | Crucell Holland B.V. | Human bind molecules capable of neutralizing influenza virus h5n1 and uses thereof |
| ES2453592T3 (es) * | 2007-08-02 | 2014-04-08 | Novimmune Sa | Anticuerpos anti-RANTES y métodos de uso de los mismos |
| KR102057826B1 (ko) * | 2008-04-11 | 2019-12-20 | 추가이 세이야쿠 가부시키가이샤 | 복수 분자의 항원에 반복 결합하는 항원 결합 분자 |
| US8187601B2 (en) | 2008-07-01 | 2012-05-29 | Aveo Pharmaceuticals, Inc. | Fibroblast growth factor receptor 3 (FGFR3) binding proteins |
| AR073770A1 (es) * | 2008-10-20 | 2010-12-01 | Imclone Llc | Anticuerpo aislado que se enlaza especificamente con, e induce la degradacion del receptor-3 del factor de crecimiento del fibroblasto humano (fgfr-3), fragmento de enlace fgfr-3 humano del mismo, composicion farmaceutica y producto que lo comprenden |
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| UA101681C2 (ru) | 2013-04-25 |
| KR20110056554A (ko) | 2011-05-30 |
| US20100098696A1 (en) | 2010-04-22 |
| EA021584B1 (ru) | 2015-07-30 |
| CA2741127C (en) | 2015-06-02 |
| BRPI0919832A8 (pt) | 2019-01-08 |
| CN103524620A (zh) | 2014-01-22 |
| CN102186884B (zh) | 2014-08-13 |
| US20120009200A1 (en) | 2012-01-12 |
| AU2009307841B2 (en) | 2013-09-12 |
| TWI381848B (zh) | 2013-01-11 |
| IL211807A0 (en) | 2011-06-30 |
| WO2010048026A3 (en) | 2010-07-15 |
| ZA201101938B (en) | 2012-08-29 |
| AR073770A1 (es) | 2010-12-01 |
| MX2011004317A (es) | 2011-06-24 |
| JP2012505912A (ja) | 2012-03-08 |
| EP2342232A2 (en) | 2011-07-13 |
| WO2010048026A2 (en) | 2010-04-29 |
| KR101370798B1 (ko) | 2014-03-14 |
| US8182815B2 (en) | 2012-05-22 |
| BRPI0919832A2 (pt) | 2015-12-15 |
| AU2009307841A1 (en) | 2010-04-29 |
| TW201026325A (en) | 2010-07-16 |
| CN102186884A (zh) | 2011-09-14 |
| US8043618B2 (en) | 2011-10-25 |
| US20120219563A1 (en) | 2012-08-30 |
| EA201170590A1 (ru) | 2011-10-31 |
| CA2741127A1 (en) | 2010-04-29 |
| US8404240B2 (en) | 2013-03-26 |
| NZ592369A (en) | 2013-02-22 |
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