JP6568110B2 - フォリスタチンポリペプチドによる障害の処置のための方法および組成物 - Google Patents
フォリスタチンポリペプチドによる障害の処置のための方法および組成物 Download PDFInfo
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- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
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- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
- C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
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- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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Landscapes
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| CA2898121A1 (en) | 2013-01-25 | 2014-07-31 | Shire Human Genetic Therapies, Inc. | Follistatin in treating duchenne muscular dystrophy |
| US10010498B2 (en) | 2014-06-04 | 2018-07-03 | Acceleron Pharma Inc. | Methods for treatment of amyotrophic lateral sclerosis with follistatin fusion proteins |
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| CN114699529A (zh) | 2014-06-13 | 2022-07-05 | 阿塞勒隆制药公司 | 用于治疗溃疡的方法和组合物 |
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| US12246042B2 (en) | 2018-08-29 | 2025-03-11 | Myos Corp. | Methods for alleviating, inhibiting or reversing muscle disuse atrophy in mammals |
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| AU2022214780A1 (en) * | 2021-01-26 | 2023-09-07 | Immunis, Inc. | Molecular superstructure and methods of use thereof |
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| US5041538A (en) | 1987-08-28 | 1991-08-20 | The Salk Institute For Biological Studies | Mammalian follistatin |
| US5182375A (en) | 1987-08-28 | 1993-01-26 | The Salk Institute For Biological Studies | DNA encoding follistatin |
| DE69233480T2 (de) | 1991-02-08 | 2006-01-05 | Progenics Pharmaceuticals, Inc. | CD4-gamma2- und CD4-IgG2-Chimären |
| EP0661993B1 (en) | 1992-09-16 | 1997-05-07 | Genentech, Inc. | Protection against liver damage by hgf |
| DE69434934D1 (de) | 1993-10-14 | 2007-04-12 | Harvard College | Verfahren zur induzierung und zur erhaltung neuronalen zellen |
| US6686198B1 (en) | 1993-10-14 | 2004-02-03 | President And Fellows Of Harvard College | Method of inducing and maintaining neuronal cells |
| US5541087A (en) | 1994-09-14 | 1996-07-30 | Fuji Immunopharmaceuticals Corporation | Expression and export technology of proteins as immunofusins |
| US5545616A (en) | 1994-09-22 | 1996-08-13 | Genentech, Inc. | Method for predicting and/or preventing preterm labor |
| GB2306481A (en) | 1995-10-21 | 1997-05-07 | Univ Manchester | Pharmaceutical comprising a stimulator of activin and/or inhibin |
| WO1999006559A1 (en) | 1997-08-01 | 1999-02-11 | The Johns Hopkins University School Of Medicine | Methods to identify growth differentiation factor (gdf) receptors |
| US6891082B2 (en) | 1997-08-01 | 2005-05-10 | The Johns Hopkins University School Of Medicine | Transgenic non-human animals expressing a truncated activintype II receptor |
| US6656475B1 (en) | 1997-08-01 | 2003-12-02 | The Johns Hopkins University School Of Medicine | Growth differentiation factor receptors, agonists and antagonists thereof, and methods of using same |
| US6004937A (en) | 1998-03-09 | 1999-12-21 | Genetics Institute, Inc. | Use of follistatin to modulate growth and differentiation factor 8 [GDF-8] and bone morphogenic protein 11 [BMP-11] |
| JP2003517580A (ja) | 1999-01-21 | 2003-05-27 | メタモーフイクス・インコーポレーテツド | 増殖分化因子インヒビター及びそれらの用途 |
| CA2365449A1 (en) | 1999-04-19 | 2000-10-26 | Kyowa Hakko Kogyo Co., Ltd. | Inhibitor of the growth of androgen-independent tumor |
| WO2001009368A1 (en) | 1999-07-30 | 2001-02-08 | The General Hospital Corporation | Follistatin antagonists |
| JP4487376B2 (ja) | 2000-03-31 | 2010-06-23 | 味の素株式会社 | 腎疾患治療剤 |
| AUPR638101A0 (en) | 2001-07-13 | 2001-08-09 | Bioa Pty Limited | Composition and method for treatment of disease |
| BR0307907A2 (pt) | 2002-02-21 | 2011-07-05 | Wyeth Corp | gasp1: proteìna contendo domìnio de folistatina |
| CN1993048A (zh) * | 2002-02-21 | 2007-07-04 | 惠氏公司 | 包含促滤泡素抑制素结构域的蛋白质 |
| PL374966A1 (en) | 2002-02-21 | 2005-11-14 | Wyeth | Follistatin domain containing proteins |
| WO2004082710A1 (en) | 2003-03-21 | 2004-09-30 | Lorantis Limited | Treatment of allergic diseases using a modulator of the notch signaling pathway |
| WO2004108157A2 (en) | 2003-06-02 | 2004-12-16 | Wyeth | Use of myostatin (gdf8) inhibitors in conjunction with corticosteroids for treating neuromuscular disorders |
| WO2005025601A1 (en) | 2003-09-15 | 2005-03-24 | Monash University | Follistatin isoforms and uses thereof |
| US7355018B2 (en) | 2003-09-30 | 2008-04-08 | Regeneron Pharmaceuticals, Inc. | Modified IGF1 polypeptides with increased stability and potency |
| WO2005032578A1 (en) | 2003-10-06 | 2005-04-14 | Monash University | Therapeutic method |
| JP4688483B2 (ja) | 2004-04-15 | 2011-05-25 | 株式会社テクノネットワーク四国 | フォリスタチン変異体ポリペプチド |
| JP2008507288A (ja) * | 2004-07-23 | 2008-03-13 | アクセルロン ファーマ インコーポレーテッド | ＡｃｔＲＩＩ受容体ポリペプチド、方法、および組成物 |
| MX2007000976A (es) | 2004-08-12 | 2007-04-10 | Wyeth Corp | Tratamiento combinado para diabetes, obesidad y enfermedades cardiovasculares utilizando inhibidores del factor 8 de crecimiento y diferenciacion. |
| NZ538097A (en) | 2005-02-07 | 2006-07-28 | Ovita Ltd | Method and compositions for improving wound healing |
| US7888486B2 (en) | 2005-08-19 | 2011-02-15 | Wyeth Llc | Antagonist antibodies against GDF-8 |
| US20070149458A1 (en) * | 2005-12-06 | 2007-06-28 | Amgen Inc. | Uses of myostatin antagonists |
| WO2008030367A2 (en) | 2006-09-01 | 2008-03-13 | The General Hospital Corporation | Selective myostatin inhibitors |
| WO2008067480A2 (en) | 2006-11-29 | 2008-06-05 | Nationwide Children's Hospital | Myostatin inhibition for enhancing muscle and/or improving muscle function |
| CA2672758C (en) | 2006-12-18 | 2019-07-30 | Acceleron Pharma Inc. | Activin-actrii antagonists and uses for increasing red blood cell levels |
| US20100028332A1 (en) | 2006-12-18 | 2010-02-04 | Acceleron Pharma Inc. | Antagonists of actriib and uses for increasing red blood cell levels |
| US8895016B2 (en) | 2006-12-18 | 2014-11-25 | Acceleron Pharma, Inc. | Antagonists of activin-actriia and uses for increasing red blood cell levels |
| EP3663318A1 (en) | 2008-01-07 | 2020-06-10 | Amgen Inc. | Method for making antibody fc-heterodimeric molecules using electrostatic steering effects |
| EP2315602A4 (en) * | 2008-06-26 | 2011-11-02 | Acceleron Pharma Inc | METHOD OF DOSING AN ACTRIIB ANTAGONIST AND MONITORING TREATED PATIENTS |
| KR20110031951A (ko) * | 2008-06-26 | 2011-03-29 | 악셀레론 파마 인코포레이티드 | 액티빈-ａｃｔｒｉｉａ의 길항물질 및 적혈구 수준을 증가시키기 위한 이들의 용도 |
| EP3202459B1 (en) * | 2009-09-09 | 2021-04-14 | Acceleron Pharma Inc. | Actriib antagonists and dosing and uses thereof for treating obesity or type 2 diabetes by regulating body fat content |
| KR101603001B1 (ko) * | 2010-08-25 | 2016-03-11 | 에프. 호프만-라 로슈 아게 | Il-18r1에 대한 항체 및 그의 용도 |
| CN103429620B (zh) | 2010-11-05 | 2018-03-06 | 酵活有限公司 | 在Fc结构域中具有突变的稳定异源二聚的抗体设计 |
| WO2013151664A1 (en) * | 2012-04-02 | 2013-10-10 | modeRNA Therapeutics | Modified polynucleotides for the production of proteins |
| ES2663993T3 (es) | 2012-05-17 | 2018-04-17 | Paranta Biosciences Limited | Uso de folistatina o de un inhibidor de activina para prevenir o tratar la disfunción del injerto de tejido |
| EP2866826B1 (en) * | 2012-06-27 | 2025-08-06 | Meiragtx UK II Limited | Combination for treating an inflammatory disorder |
| CA2898121A1 (en) * | 2013-01-25 | 2014-07-31 | Shire Human Genetic Therapies, Inc. | Follistatin in treating duchenne muscular dystrophy |
| WO2014187807A1 (en) * | 2013-05-21 | 2014-11-27 | Arcarios B.V. | Follistatin derivatives |
| US10010498B2 (en) | 2014-06-04 | 2018-07-03 | Acceleron Pharma Inc. | Methods for treatment of amyotrophic lateral sclerosis with follistatin fusion proteins |
| JP6568110B2 (ja) | 2014-06-04 | 2019-08-28 | アクセルロン ファーマ， インコーポレイテッド | フォリスタチンポリペプチドによる障害の処置のための方法および組成物 |
| CA2980757A1 (en) | 2015-03-26 | 2016-09-29 | Acceleron Pharma Inc. | Follistatin-related fusion proteins and uses thereof |
| AU2018266893A1 (en) | 2017-05-12 | 2019-12-05 | Takeda Pharmaceutical Company Limited | Recombinant follistatin-Fc fusion proteins and use in treating Duchenne muscular dystrophy |
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