JP7280182B2 - バリアントＡｃｔＲＩＩＢタンパク質およびその使用 - Google Patents
バリアントＡｃｔＲＩＩＢタンパク質およびその使用 Download PDFInfo
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Families Citing this family (22)
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| MA41052A (fr) | 2014-10-09 | 2017-08-15 | Celgene Corp | Traitement d'une maladie cardiovasculaire à l'aide de pièges de ligands d'actrii |
| SMT202300166T1 (it) | 2014-12-03 | 2023-07-20 | Celgene Corp | Antagonisti di attivina- actrii e usi per il trattamento di sindrome mielodisplastica |
| RS61881B1 (sr) | 2015-04-22 | 2021-06-30 | Biogen Ma Inc | Novi hibridni actriib proteini zamke za ligand za lečenje bolesti gubljenja mišića |
| EP3439741A4 (en) | 2016-04-06 | 2020-05-06 | Acceleron Pharma Inc. | ALK7 ANTAGONISTS AND USES THEREOF |
| JOP20190085A1 (ar) * | 2016-10-20 | 2019-04-17 | Biogen Ma Inc | طرق علاج الضمور العضلي ومرض العظام باستخدام بروتينات احتجاز مركب ترابطي actriib هجين حديثة |
| EP3538123A4 (en) | 2016-11-10 | 2020-10-14 | Keros Therapeutics, Inc. | ACTIVIN RECEPTOR TYPE IIA VARIANTS AND THEIR METHODS OF USE |
| CA3082146A1 (en) | 2017-11-09 | 2019-05-16 | Keros Therapeutics, Inc. | Activin receptor type iia variants and methods of use thereof |
| CN120399032A (zh) | 2018-01-12 | 2025-08-01 | 科乐斯疗法公司 | 激活素受体iib型变体及其使用方法 |
| JP2021522793A (ja) | 2018-05-03 | 2021-09-02 | アクセルロン ファーマ インコーポレイテッド | ＴＧＦβスーパーファミリーリガンドの多特異性バインダーおよびその使用 |
| EP3788067A4 (en) * | 2018-05-03 | 2022-01-19 | Acceleron Pharma Inc. | NOVEL BINDERS OF TGFBETA SUPERFAMILY LIGANDS AND THEIR USES |
| EP3790572A4 (en) | 2018-05-09 | 2022-03-16 | Keros Therapeutics, Inc. | ACTIVIN RECEPTOR TYPE IIA VARIANTS AND METHODS OF USE THEREOF |
| EP3807308A4 (en) * | 2018-06-15 | 2022-03-16 | Acceleron Pharma Inc. | BI AND TRIFUNCTIONAL FUSION PROTEINS AND THEIR USES |
| CN109293763B (zh) * | 2018-10-26 | 2021-10-26 | 中国农业科学院特产研究所 | 水貂激活素b蛋白及其制备与应用 |
| KR20220088699A (ko) | 2019-09-27 | 2022-06-28 | 디스크 메디슨, 인크. | 골수섬유증 및 관련 상태의 치료 방법 |
| BR112022015387A2 (pt) * | 2020-02-03 | 2022-10-11 | Acceleron Pharma Inc | Proteínas actriib variantes e usos das mesmas |
| EP4121088A4 (en) * | 2020-03-20 | 2024-07-03 | Keros Therapeutics, Inc. | Methods of using activin receptor type iib variants |
| WO2021189006A1 (en) * | 2020-03-20 | 2021-09-23 | Keros Therapeutics, Inc. | Methods of using activin receptor type iia variants |
| KR20230012539A (ko) | 2020-05-13 | 2023-01-26 | 디스크 메디슨, 인크. | 골수섬유증을 치료하기 위한 항-헤모주벨린 (hjv) 항체 |
| EP4171603A4 (en) * | 2020-06-25 | 2024-06-26 | Gliknik Inc. | ACE2-FC FUSION PROTEINS AND METHODS OF USE |
| US12186370B1 (en) | 2020-11-05 | 2025-01-07 | Celgene Corporation | ACTRIIB ligand trap compositions and uses thereof |
| EP4274600A4 (en) * | 2021-01-08 | 2024-11-20 | Acceleron Pharma Inc. | COMPOSITIONS AND METHODS FOR THE TREATMENT OF PULMONARY HYPERTENSION |
| IL314280A (en) | 2022-01-28 | 2024-09-01 | 35Pharma Inc | Type IIB activin receptor variants and their uses |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010083034A1 (en) | 2009-01-13 | 2010-07-22 | Acceleron Pharma Inc. | Methods for increasing adiponectin |
| JP2012529294A (ja) | 2009-06-12 | 2012-11-22 | アクセルロン ファーマ， インコーポレイテッド | 切断型ＡｃｔＲＩＩＢ−Ｆｃ融合タンパク質 |
| JP2014530253A (ja) | 2011-10-17 | 2014-11-17 | アクセルロンファーマ， インコーポレイテッド | 無効赤血球生成を処置するための方法および組成物 |
| JP2016135141A (ja) | 2007-02-02 | 2016-07-28 | アクセルロン ファーマ， インコーポレイテッド | ＡｃｔＲＩＩＢから誘導されたバリアントおよびその使用 |
Family Cites Families (50)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3382562D1 (de) | 1982-09-24 | 1992-06-25 | Us Health | Wiederherstellung von gewebe bei tieren. |
| NZ210699A (en) | 1984-01-04 | 1989-06-28 | Int Genetic Eng | Isolation of an osteogenic protein of the p3 immunologically related family |
| EP0169016B2 (en) | 1984-07-16 | 2004-04-28 | Celtrix Pharmaceuticals, Inc. | Polypeptide cartilage-inducing factors found in bone |
| EP0272253A4 (en) | 1986-03-07 | 1990-02-05 | Massachusetts Inst Technology | METHOD FOR IMPROVING GLYCOPROTE INSTABILITY. |
| US5080891A (en) | 1987-08-03 | 1992-01-14 | Ddi Pharmaceuticals, Inc. | Conjugates of superoxide dismutase coupled to high molecular weight polyalkylene glycols |
| US20050186593A1 (en) * | 1991-05-10 | 2005-08-25 | The Salk Institute For Biological Studies | Cloning and recombinant production of CRF receptor(s) |
| US5932448A (en) | 1991-11-29 | 1999-08-03 | Protein Design Labs., Inc. | Bispecific antibody heterodimers |
| US5677196A (en) | 1993-05-18 | 1997-10-14 | University Of Utah Research Foundation | Apparatus and methods for multi-analyte homogeneous fluoro-immunoassays |
| US5525490A (en) | 1994-03-29 | 1996-06-11 | Onyx Pharmaceuticals, Inc. | Reverse two-hybrid method |
| US5814565A (en) | 1995-02-23 | 1998-09-29 | University Of Utah Research Foundation | Integrated optic waveguide immunosensor |
| US5731168A (en) | 1995-03-01 | 1998-03-24 | Genentech, Inc. | Method for making heteromultimeric polypeptides |
| CA2217545A1 (en) | 1995-04-11 | 1996-10-17 | Marc Vidal | Reverse two-hybrid systems |
| US20020062010A1 (en) | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
| CA2297489A1 (en) | 1997-07-30 | 1999-02-11 | Emory University | Novel bone mineralization proteins, dna, vectors, expression systems |
| BR0008188A (pt) | 1999-01-21 | 2002-02-13 | Metamorphix Inc | Inibidores de fator de diferenciação de crescimento e usos para os mesmos |
| EP1729793B1 (en) | 2004-03-02 | 2015-07-22 | Acceleron Pharma Inc. | Alk7 and myostatin inhibitors for muscle wasting disorders |
| ES2551852T3 (es) | 2004-07-23 | 2015-11-24 | Acceleron Pharma Inc. | Polipéptidos del receptor ActRII |
| WO2007147901A1 (en) | 2006-06-22 | 2007-12-27 | Novo Nordisk A/S | Production of bispecific antibodies |
| US20100028332A1 (en) | 2006-12-18 | 2010-02-04 | Acceleron Pharma Inc. | Antagonists of actriib and uses for increasing red blood cell levels |
| EP2468291B1 (en) | 2006-12-18 | 2017-11-22 | Acceleron Pharma, Inc. | Activin-actrii antagonists and uses for increasing red blood cell levels |
| PT2235064E (pt) | 2008-01-07 | 2016-03-01 | Amgen Inc | Método de preparação de moléculas heterodiméricas de fc de anticorpos utilizando efeitos de indução eletrostática |
| TWI586364B (zh) | 2008-05-02 | 2017-06-11 | 艾西利羅製藥公司 | 調節血管新生與周圍細胞組成的方法與組合物 |
| NZ590326A (en) | 2008-06-26 | 2013-05-31 | Acceleron Pharma Inc | Antagonists of activin-actriia and uses for increasing red blood cell levels |
| JP5922928B2 (ja) | 2008-08-14 | 2016-05-24 | アクセルロン ファーマ， インコーポレイテッド | 赤血球レベルを高めるためのｇｄｆトラップの使用 |
| US8216997B2 (en) | 2008-08-14 | 2012-07-10 | Acceleron Pharma, Inc. | Methods for increasing red blood cell levels and treating anemia using a combination of GDF traps and erythropoietin receptor activators |
| CN102548617B (zh) | 2009-03-30 | 2017-11-07 | 阿塞勒隆制药公司 | Bmp‑alk3拮抗剂和促进骨生长的用途 |
| ES2796121T3 (es) | 2009-08-13 | 2020-11-25 | Acceleron Pharma Inc | Uso combinado de trampas de GDF y activadores del receptor de la eritropoyetina para aumentar los niveles de glóbulos rojos |
| CA2773494A1 (en) * | 2009-09-09 | 2011-03-17 | Acceleron Pharma Inc. | Actriib antagonists and dosing and uses thereof |
| CA2781519A1 (en) | 2009-09-16 | 2011-03-24 | Genentech, Inc. | Coiled coil and/or tether containing protein complexes and uses thereof |
| WO2012027065A2 (en) | 2010-08-27 | 2012-03-01 | Celgene Corporation | Combination therapy for treatment of disease |
| CN102850458B (zh) | 2011-06-28 | 2014-10-01 | 华博生物医药技术（上海）有限公司 | 新型重组双功能融合蛋白及其制法和用途 |
| WO2013063536A1 (en) | 2011-10-27 | 2013-05-02 | Acceleron Pharma, Inc. | Actriib binding agents and uses thereof |
| CN105658672A (zh) | 2013-08-22 | 2016-06-08 | 阿塞勒隆制药公司 | TGF-β受体II型变体及其用途 |
| KR102520970B1 (ko) * | 2014-03-21 | 2023-04-12 | 악셀레론 파마 인코포레이티드 | 액티빈 b 및/또는 gdf11을 억제함으로써 적혈 혈액 세포 수준을 증가시키고 비효율적인 적혈구 생성을 치료하는 방법 |
| JP6649895B2 (ja) * | 2014-04-18 | 2020-02-19 | アクセルロン ファーマ， インコーポレイテッド | 赤血球レベルを増加させ、そして鎌状赤血球症を処置するための方法 |
| AU2015274277B2 (en) * | 2014-06-13 | 2021-03-18 | Acceleron Pharma, Inc. | Methods and compositions for treating ulcers |
| SMT202300166T1 (it) | 2014-12-03 | 2023-07-20 | Celgene Corp | Antagonisti di attivina- actrii e usi per il trattamento di sindrome mielodisplastica |
| MA41919A (fr) | 2015-04-06 | 2018-02-13 | Acceleron Pharma Inc | Hétéromultimères alk4:actriib et leurs utilisations |
| BR112017021510A2 (pt) | 2015-04-06 | 2018-07-03 | Acceleron Pharma Inc | heteromultímeros do receptor tipo i e tipo ii da superfamília tgf-beta e sua utilização |
| JP6810702B2 (ja) | 2015-04-06 | 2021-01-06 | アクセルロン ファーマ インコーポレイテッド | シングルアームｉ型およびｉｉ型受容体融合タンパク質およびその使用 |
| RS61881B1 (sr) | 2015-04-22 | 2021-06-30 | Biogen Ma Inc | Novi hibridni actriib proteini zamke za ligand za lečenje bolesti gubljenja mišića |
| WO2016205370A1 (en) | 2015-06-15 | 2016-12-22 | Santa Maria Biotherapeutics, Inc. | Methods of using activin receptor iib-based proteins |
| EP3344660B1 (en) | 2015-08-31 | 2025-03-05 | National Research Council of Canada | Tgf-beta-receptor ectodomain fusion molecules and uses thereof |
| EP3439741A4 (en) | 2016-04-06 | 2020-05-06 | Acceleron Pharma Inc. | ALK7 ANTAGONISTS AND USES THEREOF |
| AU2017293778B2 (en) | 2016-07-07 | 2022-03-24 | Acceleron Pharma Inc. | TGF-beta superfamily heteromultimers and uses thereof |
| WO2018067874A1 (en) | 2016-10-05 | 2018-04-12 | Acceleron Pharma Inc. | Variant actriib proteins and uses thereof |
| EP3522913A4 (en) | 2016-10-05 | 2020-10-28 | Acceleron Pharma Inc. | ALK4 HETEROMULTIMERS: ACTRIIB AND THEIR USES |
| AU2017338915B2 (en) | 2016-10-05 | 2024-11-21 | Acceleron Pharma Inc. | TGF-beta superfamily type I and type II receptor heteromultimers and uses thereof |
| JOP20190085A1 (ar) | 2016-10-20 | 2019-04-17 | Biogen Ma Inc | طرق علاج الضمور العضلي ومرض العظام باستخدام بروتينات احتجاز مركب ترابطي actriib هجين حديثة |
| EP3538123A4 (en) | 2016-11-10 | 2020-10-14 | Keros Therapeutics, Inc. | ACTIVIN RECEPTOR TYPE IIA VARIANTS AND THEIR METHODS OF USE |
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- 2017-10-05 MA MA046471A patent/MA46471A/fr unknown
- 2017-10-05 CN CN201780074935.6A patent/CN110036025B/zh active Active
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016135141A (ja) | 2007-02-02 | 2016-07-28 | アクセルロン ファーマ， インコーポレイテッド | ＡｃｔＲＩＩＢから誘導されたバリアントおよびその使用 |
| WO2010083034A1 (en) | 2009-01-13 | 2010-07-22 | Acceleron Pharma Inc. | Methods for increasing adiponectin |
| JP2012529294A (ja) | 2009-06-12 | 2012-11-22 | アクセルロン ファーマ， インコーポレイテッド | 切断型ＡｃｔＲＩＩＢ−Ｆｃ融合タンパク質 |
| JP2014530253A (ja) | 2011-10-17 | 2014-11-17 | アクセルロンファーマ， インコーポレイテッド | 無効赤血球生成を処置するための方法および組成物 |
Non-Patent Citations (2)
| Title |
|---|
| Greenwald J. et al.，Identification of a binding site on the type II activin receptor for activin and inhibin.，The Journal of biological chemistry，2000年，275(5)，3206-3212 |
| SAKO Dianne et al.，Characterization of the Ligand Binding Functionality of the Extracellular Domain of Activin Receptor Type IIB.，The Journal of biological chemistry，2010年，285(27)，21037-21048 |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2023033573A (ja) * | 2016-10-05 | 2023-03-10 | アクセルロン ファーマ インコーポレイテッド | バリアントＡｃｔＲＩＩＢタンパク質およびその使用 |
| JP7617962B2 (ja) | 2016-10-05 | 2025-01-20 | アクセルロン ファーマ インコーポレイテッド | バリアントＡｃｔＲＩＩＢタンパク質およびその使用 |
| US12240887B2 (en) | 2016-10-05 | 2025-03-04 | Acceleron Pharma Inc. | Variant ActRIIB proteins and uses thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CA3039525A1 (en) | 2018-04-12 |
| CN110036025A (zh) | 2019-07-19 |
| EP3523328A4 (en) | 2020-04-01 |
| KR102761094B1 (ko) | 2025-02-03 |
| AU2017338916B2 (en) | 2022-03-24 |
| US11267865B2 (en) | 2022-03-08 |
| MA46471A (fr) | 2021-05-19 |
| BR112019006918A2 (pt) | 2019-06-25 |
| KR102595559B1 (ko) | 2023-10-30 |
| JP7617962B2 (ja) | 2025-01-20 |
| CN110036025B (zh) | 2024-03-22 |
| US12240887B2 (en) | 2025-03-04 |
| JP2023033573A (ja) | 2023-03-10 |
| AU2024200684A1 (en) | 2024-02-22 |
| WO2018067874A1 (en) | 2018-04-12 |
| AU2017338916A1 (en) | 2019-04-18 |
| US20200055919A1 (en) | 2020-02-20 |
| JP2019536440A (ja) | 2019-12-19 |
| KR20230152811A (ko) | 2023-11-03 |
| EP3523328A1 (en) | 2019-08-14 |
| KR20190073414A (ko) | 2019-06-26 |
| US20220306724A1 (en) | 2022-09-29 |
| AU2022201698A1 (en) | 2022-04-07 |
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