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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Classifications
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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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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- C07K14/475—Growth factors; Growth regulators
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- C07K2319/00—Fusion polypeptide
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Landscapes
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| US20100015144A1 (en) | 2008-06-26 | 2010-01-21 | Acceleron Pharma Inc. | Methods for dosing an activin-actriia antagonist and monitoring of treated patients |
| EA201590719A1 (ru) | 2013-01-25 | 2015-12-30 | Шир Хьюман Дженетик Терапис, Инк. | Фоллистатин в лечении мышечной дистрофии дюшенна |
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| JP2018510637A (ja) * | 2015-03-26 | 2018-04-19 | アクセルロン ファーマ， インコーポレイテッド | フォリスタチン関連融合タンパク質およびその使用 |
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| WO2019178759A1 (zh) * | 2018-03-21 | 2019-09-26 | 维多利亚生物医学控股股份有限公司 | 促进局部肌肉增长、减缓或防止局部肌肉萎缩的组合物及其用途 |
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| WO2022098812A1 (en) | 2020-11-04 | 2022-05-12 | Keros Therapeutics, Inc. | Methods of treating iron overload |
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| US5182375A (en) | 1987-08-28 | 1993-01-26 | The Salk Institute For Biological Studies | DNA encoding follistatin |
| US5041538A (en) | 1987-08-28 | 1991-08-20 | The Salk Institute For Biological Studies | Mammalian follistatin |
| ATE288923T1 (de) * | 1991-02-08 | 2005-02-15 | Progenics Pharm Inc | Cd4-gamma2- und cd4-igg2-chimären |
| WO1994006456A1 (en) | 1992-09-16 | 1994-03-31 | Genentech, Inc. | Protection against liver damage by hgf |
| US6686198B1 (en) | 1993-10-14 | 2004-02-03 | President And Fellows Of Harvard College | Method of inducing and maintaining neuronal cells |
| JPH09503673A (ja) | 1993-10-14 | 1997-04-15 | プレジデント・アンド・フエローズ・オブ・ハーバード・カレツジ | ニューロン細胞の誘導および維持法 |
| 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 |
| 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 |
| 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 |
| 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] |
| DE60027135T2 (de) | 1999-01-21 | 2007-01-11 | Metamorphix, Inc. | Inhibitoren für wachstumdifferenzierungsfaktor und ihre anwendungen |
| EP1174149A1 (en) | 1999-04-19 | 2002-01-23 | Kyowa Hakko Kogyo Co., Ltd. | Proliferation inhibitor for 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 |
| 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 |
| JP4429729B2 (ja) | 2002-02-21 | 2010-03-10 | ワイス エルエルシー | Ｇａｓｐ１；フォリスタチンドメイン含有タンパク質 |
| JP4429728B2 (ja) | 2002-02-21 | 2010-03-10 | ワイス エルエルシー | フォリスタチン（ｆｏｌｌｉｓｔａｔｉｎ）ドメイン含有タンパク質 |
| ATE474593T1 (de) | 2003-03-21 | 2010-08-15 | Celldex Therapeutics Ltd | Behandlung von allergischen erkrankungen unter verwendung eines modulators des notch signaling pathway |
| JP5110877B2 (ja) | 2003-06-02 | 2012-12-26 | ワイス・エルエルシー | 神経筋障害を処置するための、コルチコステロイドと組み合わせたミオスタチン（ｇｄｆ８）インヒビターの使用 |
| US20070135336A1 (en) | 2003-09-15 | 2007-06-14 | De Kretser David | 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 |
| EP1771470B1 (en) | 2004-07-23 | 2013-06-26 | Acceleron Pharma Inc. | Actrii receptor polypeptides, methods and compositions |
| EP1778275A2 (en) | 2004-08-12 | 2007-05-02 | Wyeth | Combination therapy for diabetes, obesity, and cardiovascular diseases using gdf-8 inhibitors |
| NZ538097A (en) | 2005-02-07 | 2006-07-28 | Ovita Ltd | Method and compositions for improving wound healing |
| AU2006283725B2 (en) | 2005-08-19 | 2012-02-16 | The Trustees Of The University Of Pennsylvania | Antagonist antibodies against GDF-8 and uses in treatment of ALS and other GDF-8-associated disorders |
| MX2008007324A (es) | 2005-12-06 | 2009-03-04 | Amgen Inc | Usos de antagonistas de miostatina. |
| WO2008030367A2 (en) | 2006-09-01 | 2008-03-13 | The General Hospital Corporation | Selective myostatin inhibitors |
| EP2097095B1 (en) | 2006-11-29 | 2016-01-27 | Nationwide Children's Hospital | Myostatin inhibition for enhancing muscle and/or improving muscle function |
| US20100028332A1 (en) | 2006-12-18 | 2010-02-04 | Acceleron Pharma Inc. | Antagonists of actriib and uses for increasing red blood cell levels |
| EP2468290B1 (en) | 2006-12-18 | 2015-04-01 | Acceleron Pharma, Inc. | Activin-ActRII Antagonists for use in treating anemia |
| US8895016B2 (en) | 2006-12-18 | 2014-11-25 | Acceleron Pharma, Inc. | Antagonists of activin-actriia and uses for increasing red blood cell levels |
| DK2235064T3 (en) | 2008-01-07 | 2016-01-11 | Amgen Inc | A process for the preparation of heterodimeric Fc molecules using electrostatic control effects |
| US20100015144A1 (en) * | 2008-06-26 | 2010-01-21 | Acceleron Pharma Inc. | Methods for dosing an activin-actriia antagonist and monitoring of treated patients |
| JP5773868B2 (ja) * | 2008-06-26 | 2015-09-02 | アクセルロン ファーマ， インコーポレイテッド | アクチビン−ＡｃｔＲＩＩａのアンタゴニストおよび赤血球レベルを高めるためのその使用 |
| MX340451B (es) * | 2009-09-09 | 2016-07-08 | Acceleron Pharma Inc | Antagonistas de actriib y dosificacion y usos de los mismos. |
| JP5813114B2 (ja) * | 2010-08-25 | 2015-11-17 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | Ｉｌ−１８ｒ１に対する抗体およびその使用 |
| MX352929B (es) | 2010-11-05 | 2017-12-13 | Zymeworks Inc | DISEÑO DE ANTICUERPOS HETERODIMÉRICOS ESTABLES CON MUTACIONES EN EL DOMINIO Fc. |
| EP2834260A4 (en) | 2012-04-02 | 2016-08-10 | Moderna Therapeutics Inc | MODIFIED POLYNUCLEOTIDES FOR THE PREPARATION OF MEMBRANE 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 |
| ES3049487T3 (en) * | 2012-06-27 | 2025-12-16 | Meiragtx Uk Ii Ltd | Combination for treating an inflammatory disorder |
| EA201590719A1 (ru) * | 2013-01-25 | 2015-12-30 | Шир Хьюман Дженетик Терапис, Инк. | Фоллистатин в лечении мышечной дистрофии дюшенна |
| 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 |
| JP2018510637A (ja) | 2015-03-26 | 2018-04-19 | アクセルロン ファーマ， インコーポレイテッド | フォリスタチン関連融合タンパク質およびその使用 |
| JP2020519291A (ja) | 2017-05-12 | 2020-07-02 | シャイアー ヒューマン ジェネティック セラピーズ インコーポレイテッド | 組み換えフォリスタチン−ｆｃ融合タンパク質およびデュシェンヌ型筋ジストロフィーの治療における使用 |
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