BR112012029986B1 - Anticorpo humano isolado ou fragmento de ligação ao antígeno do mesmo que se liga especificamente ou bloqueia a atividade biológica de gdf8 humano maduro do tipo selvagem, composição farmacêutica e usos dos mesmos - Google Patents
Anticorpo humano isolado ou fragmento de ligação ao antígeno do mesmo que se liga especificamente ou bloqueia a atividade biológica de gdf8 humano maduro do tipo selvagem, composição farmacêutica e usos dos mesmos Download PDFInfo
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| US34855910P | 2010-05-26 | 2010-05-26 | |
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| US61/372,882 | 2010-08-12 | ||
| PCT/US2011/037837 WO2011150008A1 (en) | 2010-05-26 | 2011-05-25 | Antibodies to human gdf8 |
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Families Citing this family (74)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101479381B (zh) | 2006-03-31 | 2015-04-29 | 中外制药株式会社 | 调控抗体血液动力学的方法 |
| PL2202245T3 (pl) | 2007-09-26 | 2017-02-28 | Chugai Seiyaku Kabushiki Kaisha | Sposób modyfikowania punktu izoelektrycznego przeciwciała poprzez podstawienie aminokwasu w cdr |
| CN102056946A (zh) | 2008-04-11 | 2011-05-11 | 中外制药株式会社 | 与多个分子的抗原反复结合的抗原结合分子 |
| JO3340B1 (ar) | 2010-05-26 | 2019-03-13 | Regeneron Pharma | مضادات حيوية لـعامل تمايز النمو 8 البشري |
| NZ608206A (en) | 2010-08-16 | 2015-02-27 | Amgen Inc | Antibodies that bind myostatin, compositions and methods |
| EP4231014A3 (en) | 2010-11-30 | 2024-08-14 | Chugai Seiyaku Kabushiki Kaisha | Antigen-binding molecule capable of binding to plurality of antigen molecules repeatedly |
| AU2012339722B2 (en) | 2011-11-14 | 2017-09-14 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for increasing muscle mass and muscle strength by specifically antagonizing GDF8 and/or Activin A |
| JO3820B1 (ar) * | 2012-05-03 | 2021-01-31 | Regeneron Pharma | أجسام مضادة بشرية لـ fel d1وطرق لاستخدامها |
| TWI641687B (zh) | 2012-05-29 | 2018-11-21 | 美商再生元醫藥公司 | 生產細胞株增強子 |
| WO2014030728A1 (ja) | 2012-08-24 | 2014-02-27 | 中外製薬株式会社 | FcγRIIb特異的Fc領域改変体 |
| EP2889376A4 (en) | 2012-08-24 | 2016-11-02 | Chugai Pharmaceutical Co Ltd | ANTIBODIES Fc SPECIFIC TO FCTRII OF MOUSE |
| PT3835310T (pt) | 2012-09-13 | 2024-05-20 | Bristol Myers Squibb Co | Proteínas de domínio de estrutura à base de fibronectina que ligam à miostatina |
| AU2013334660B2 (en) | 2012-10-24 | 2018-08-09 | Celgene Corporation | Methods for treating anemia |
| JP6463331B2 (ja) | 2013-03-15 | 2019-01-30 | イントリンシック ライフサイエンシズ リミテッド ライアビリティ カンパニー | 抗ヘプシジン抗体およびその使用 |
| AR095196A1 (es) | 2013-03-15 | 2015-09-30 | Regeneron Pharma | Medio de cultivo celular libre de suero |
| CN105246914B (zh) | 2013-04-02 | 2021-08-27 | 中外制药株式会社 | Fc区变体 |
| EP2981822B1 (en) | 2013-05-06 | 2020-09-02 | Scholar Rock, Inc. | Compositions and methods for growth factor modulation |
| TWI655207B (zh) | 2013-07-30 | 2019-04-01 | 再生元醫藥公司 | 抗活化素ａ之抗體及其用途 |
| CA2922113C (en) | 2013-08-23 | 2023-05-23 | Regeneron Pharmaceuticals, Inc. | Diagnostic tests and methods for assessing safety, efficacy or outcome of allergen-specific immunotherapy (sit) |
| AU2015321462B2 (en) | 2014-09-22 | 2020-04-30 | Intrinsic Lifesciences Llc | Humanized anti-hepcidin antibodies and uses thereof |
| WO2016073853A1 (en) | 2014-11-06 | 2016-05-12 | Scholar Rock, Inc. | Anti-pro/latent-myostatin antibodies and uses thereof |
| SG11201703748PA (en) | 2014-11-24 | 2017-06-29 | Somalogic Inc | Nucleic acid compounds for binding growth differentiation factor 11 |
| NZ730607A (en) | 2014-12-19 | 2022-07-01 | Chugai Pharmaceutical Co Ltd | Anti-myostatin antibodies, polypeptides containing variant fc regions, and methods of use |
| MX2017008978A (es) | 2015-02-05 | 2017-10-25 | Chugai Pharmaceutical Co Ltd | Anticuerpos que comprenden un dominio de union al antigeno dependiente de la concentracion ionica, variantes de la region fc, antiocuerpor de union a interleucina 8 (il-8) y usos de los mismos. |
| WO2016128523A1 (en) | 2015-02-12 | 2016-08-18 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for predicting the responsiveness of a patient affected with malignant hematological disease to chemotherapy treatment and methods of treatment of such disease |
| EA201792298A1 (ru) * | 2015-04-15 | 2018-04-30 | Регенерон Фармасьютикалз, Инк. | Способы увеличения силы и функциональности с помощью ингибиторов gdf8 |
| TW202330904A (zh) | 2015-08-04 | 2023-08-01 | 美商再生元醫藥公司 | 補充牛磺酸之細胞培養基及用法 |
| EP4461312A2 (en) | 2015-09-15 | 2024-11-13 | Scholar Rock, Inc. | Anti-pro/latent-myostatin antibodies and uses thereof |
| JP7141336B2 (ja) | 2015-12-25 | 2022-09-22 | 中外製薬株式会社 | 抗ミオスタチン抗体および使用方法 |
| KR20180094110A (ko) | 2016-01-08 | 2018-08-22 | 스칼러 락, 인크. | 항-프로/잠재성 미오스타틴 항체 및 그의 사용 방법 |
| IL301468A (en) | 2016-06-13 | 2023-05-01 | Scholar Rock Inc | Use of myostatin inhibitors and combined treatments |
| KR102538749B1 (ko) | 2016-08-05 | 2023-06-01 | 추가이 세이야쿠 가부시키가이샤 | Il-8 관련 질환의 치료용 또는 예방용 조성물 |
| WO2018039499A1 (en) | 2016-08-24 | 2018-03-01 | Regeneron Pharmaceuticals, Inc. | Host cell protein modification |
| CN106770517A (zh) * | 2016-12-16 | 2017-05-31 | 青岛科技大学 | 一种检测力竭运动后小鼠骨骼肌肌肉生长抑制素含量的方法 |
| EP3558347A1 (en) | 2016-12-22 | 2019-10-30 | Regeneron Pharmaceuticals, Inc. | Method of treating an allergy with allergen-specific monoclonal antibodies |
| DK3565592T5 (da) | 2017-01-06 | 2024-09-02 | Scholar Rock Inc | Behandling af stofskiftesygdomme ved inhibering af myostatinaktivering |
| CA3067847A1 (en) | 2017-07-06 | 2019-01-10 | Regeneron Pharmaceuticals, Inc. | Cell culture process for making a glycoprotein |
| MX2020006639A (es) | 2017-12-22 | 2020-09-14 | Regeneron Pharma | Sistema y metodo para caracterizar las impurezas de un producto farmaceutico. |
| WO2019129679A1 (en) * | 2017-12-29 | 2019-07-04 | F. Hoffmann-La Roche Ag | Method for improving vegf-receptor blocking selectivity of an anti-vegf antibody |
| AU2019215363A1 (en) | 2018-01-31 | 2020-07-23 | Regeneron Pharmaceuticals, Inc. | System and method for characterizing size and charge variant drug product impurities |
| TW202311746A (zh) | 2018-02-02 | 2023-03-16 | 美商再生元醫藥公司 | 用於表徵蛋白質二聚合之系統及方法 |
| KR20200127979A (ko) | 2018-02-28 | 2020-11-11 | 리제너론 파마슈티칼스 인코포레이티드 | 바이러스 오염물질을 확인하기 위한 시스템 및 방법 |
| KR20200128125A (ko) | 2018-03-01 | 2020-11-11 | 리제너론 파아마슈티컬스, 인크. | 신체 조성을 변경하기 위한 방법 |
| ES2969882T3 (es) | 2018-03-19 | 2024-05-23 | Regeneron Pharma | Ensayos y reactivos de electroforesis capilar en microchip |
| TW202016125A (zh) | 2018-05-10 | 2020-05-01 | 美商再生元醫藥公司 | 用於定量及調節蛋白質黏度之系統與方法 |
| EA202092684A1 (ru) | 2018-08-27 | 2021-03-11 | Ридженерон Фармасьютикалз, Инк. | Применение рамановской спектроскопии для последующей очистки |
| BR112020026348A2 (pt) | 2018-08-30 | 2021-03-30 | Regeneron Pharmaceuticals, Inc. | Método para avaliar a estequiometria e distribuição de tamanho de complexos de proteínas, para selecionar um medicamento de proteína principal e para caracterizar complexos de proteínas, e, composição farmacêutica |
| CA3123024A1 (en) * | 2018-12-18 | 2020-06-25 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for enhancing body weight and lean muscle mass using antagonists against leptin receptor, gdf8 and activin a |
| KR20210114926A (ko) | 2019-01-16 | 2021-09-24 | 리제너론 파마슈티칼스 인코포레이티드 | 단백질 내에서 유리 티올을 식별하는 방법 |
| AU2020275406A1 (en) | 2019-05-13 | 2021-11-18 | Regeneron Pharmaceuticals, Inc. | Improved competitive ligand binding assays |
| AU2020352547A1 (en) | 2019-09-24 | 2022-03-31 | Regeneron Pharmaceuticals, Inc. | Systems and methods for chromatography use and regeneration |
| MX2022006236A (es) | 2019-11-25 | 2022-06-22 | Regeneron Pharma | Formulaciones de liberacion sostenida con emulsiones no acuosas. |
| WO2021142269A1 (en) * | 2020-01-10 | 2021-07-15 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for modulation of genes associated with muscle atrophy |
| WO2021142331A1 (en) * | 2020-01-10 | 2021-07-15 | Dyne Therapeutics, Inc. | Muscle targeting complexes and uses thereof for modulation of genes associated with cardiac muscle disease |
| KR20230088853A (ko) | 2020-01-21 | 2023-06-20 | 리제너론 파마슈티칼스 인코포레이티드 | 당질화된 단백질의 전기영동을 위한 탈당질화 방법 |
| US20220064591A1 (en) | 2020-08-31 | 2022-03-03 | Regeneron Pharmaceuticals, Inc. | Asparagine feed strategies to improve cell culture performance and mitigate asparagine sequence variants |
| IL303027A (en) | 2020-11-25 | 2023-07-01 | Regeneron Pharma | Sustained release formulations by creating a non-aqueous membrane emulsion |
| JP2024500409A (ja) | 2020-12-17 | 2024-01-09 | リジェネロン・ファーマシューティカルズ・インコーポレイテッド | タンパク質封入マイクロゲルの作製 |
| US12031151B2 (en) | 2021-01-20 | 2024-07-09 | Regeneron Pharmaceuticals, Inc. | Methods of improving protein titer in cell culture |
| EP4302098A1 (en) | 2021-03-03 | 2024-01-10 | Regeneron Pharmaceuticals, Inc. | Systems and methods for quantifying and modifying protein viscosity |
| EP4315344A1 (en) | 2021-03-26 | 2024-02-07 | Regeneron Pharmaceuticals, Inc. | Methods and systems for developing mixing protocols |
| BR112023024984A2 (pt) | 2021-06-01 | 2024-02-20 | Regeneron Pharma | Tampão de amostra de eletroforese aquosa, método para identificar contaminantes ou impurezas em uma amostra de droga proteica, e, kit |
| US20230077710A1 (en) | 2021-09-08 | 2023-03-16 | Regeneron Pharmaceuticals, Inc. | HIGH-THROUGHPUT AND MASS-SPECTROMETRY-BASED METHOD FOR QUANTITATING ANTIBODIES AND OTHER Fc-CONTAINING PROTEINS |
| CA3232463A1 (en) | 2021-09-20 | 2023-03-23 | Philip Mellors | Methods of controlling antibody heterogeneity |
| IL311248A (en) | 2021-10-07 | 2024-05-01 | Regeneron Pharma | PH meter calibration and repair |
| WO2023059800A2 (en) | 2021-10-07 | 2023-04-13 | Regeneron Pharmaceuticals, Inc. | Systems and methods of ph modeling and control |
| AU2022376179A1 (en) | 2021-10-26 | 2024-05-16 | Regeneron Pharmaceuticals, Inc. | Systems and methods for generating laboratory water and distributing laboratory water at different temperatures |
| WO2023177836A1 (en) | 2022-03-18 | 2023-09-21 | Regeneron Pharmaceuticals, Inc. | Methods and systems for analyzing polypeptide variants |
| WO2024064842A1 (en) | 2022-09-21 | 2024-03-28 | Regeneron Pharmaceuticals, Inc. | Methods of treating obesity, diabetes, and liver dysfunction |
| US20240198253A1 (en) | 2022-12-16 | 2024-06-20 | Regeneron Pharmaceuticals, Inc. | Methods and systems for assessing chromatographic column integrity |
| WO2024158880A1 (en) | 2023-01-25 | 2024-08-02 | Regeneron Pharmaceuticals, Inc. | Methods of modeling liquid protein composition stability |
| US20240248097A1 (en) | 2023-01-25 | 2024-07-25 | Regeneron Pharmaceuticals, Inc. | Mass spectrometry-based characterization of antibodies co-expressed in vivo |
| WO2024163708A1 (en) | 2023-02-01 | 2024-08-08 | Regeneron Pharmaceuticals, Inc. | Asymmetrical flow field-flow fractionation with mass spectrometry for biomacromolecule analysis |
| WO2024178213A2 (en) | 2023-02-22 | 2024-08-29 | Regeneron Pharmaceuticals, Inc. | System suitability parameters and column aging |
Family Cites Families (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL85035A0 (en) | 1987-01-08 | 1988-06-30 | Int Genetic Eng | Polynucleotide molecule,a chimeric antibody with specificity for human b cell surface antigen,a process for the preparation and methods utilizing the same |
| ATE255131T1 (de) | 1991-06-14 | 2003-12-15 | Genentech Inc | Humanisierter heregulin antikörper |
| DE69432815T2 (de) | 1993-03-19 | 2003-12-11 | The Johns Hopkins University School Of Medicine, Baltimore | Wachstumsfaktor-8 |
| US5994618A (en) | 1997-02-05 | 1999-11-30 | Johns Hopkins University School Of Medicine | Growth differentiation factor-8 transgenic mice |
| DE69941116D1 (de) | 1998-05-06 | 2009-08-27 | Metamorphix Inc | G von gdf-8 |
| IL146845A0 (en) | 1999-07-20 | 2002-07-25 | Pharmexa As | Method for down-regulating gdf-8 activity |
| US7320789B2 (en) | 2001-09-26 | 2008-01-22 | Wyeth | Antibody inhibitors of GDF-8 and uses thereof |
| US7261893B2 (en) * | 2002-10-22 | 2007-08-28 | Wyeth | Neutralizing antibodies against GDF-8 and uses therefor |
| US20040101920A1 (en) | 2002-11-01 | 2004-05-27 | Czeslaw Radziejewski | Modification assisted profiling (MAP) methodology |
| ES2359562T3 (es) * | 2002-12-20 | 2011-05-24 | Amgen, Inc. | Agentes de unión que inhiben miostatina. |
| WO2004108157A2 (en) | 2003-06-02 | 2004-12-16 | Wyeth | Use of myostatin (gdf8) inhibitors in conjunction with corticosteroids for treating neuromuscular disorders |
| WO2005066204A2 (en) | 2003-12-31 | 2005-07-21 | Schering-Plough Ltd. | Neutralizing epitope-based growth enhancing vaccine |
| EP3006039B1 (en) | 2004-03-02 | 2021-01-06 | Acceleron Pharma Inc. | Alk7 polypeptides for use in promoting fat loss |
| WO2005094446A2 (en) * | 2004-03-23 | 2005-10-13 | Eli Lilly And Company | Anti-myostatin antibodies |
| US7850962B2 (en) | 2004-04-20 | 2010-12-14 | Genmab A/S | Human monoclonal antibodies against CD20 |
| CN101001642A (zh) | 2004-08-12 | 2007-07-18 | 惠氏公司 | 使用gdf－8抑制剂对糖尿病、肥胖症和心血管病的联合治疗 |
| NZ538097A (en) | 2005-02-07 | 2006-07-28 | Ovita Ltd | Method and compositions for improving wound healing |
| DOP2006000093A (es) * | 2005-04-25 | 2007-01-31 | Pfizer | Anticuerpos contra miostatina |
| ES2659114T3 (es) | 2005-08-19 | 2018-03-13 | Wyeth Llc | Anticuerpos antagonistas contra GDF-8 y usos en el tratamiento de ALS y otros trastornos asociados con GDF-8 |
| US7635760B2 (en) | 2005-10-06 | 2009-12-22 | Eli Lilly And Company | Anti-myostatin antibodies |
| UA92504C2 (en) | 2005-10-12 | 2010-11-10 | Эли Лилли Энд Компани | Anti-myostatin monoclonal antibody |
| EP1968621A2 (en) | 2005-12-06 | 2008-09-17 | Amgen Inc. | Uses of myostatin antagonists |
| US7699146B1 (en) | 2006-04-02 | 2010-04-20 | Fox Factory, Inc. | Suspension damper having inertia valve and user adjustable pressure-relief |
| DK2041177T3 (da) | 2006-06-02 | 2012-02-27 | Regeneron Pharma | Højaffinitetsantistoffer mod human IL-6-receptor |
| JP2009545313A (ja) * | 2006-08-03 | 2009-12-24 | オリコ・リミテッド | ミオスタチンアンタゴニスト |
| EA015916B1 (ru) | 2006-09-05 | 2011-12-30 | Эли Лилли Энд Компани | Моноклональные антитела к миостатину и их применения |
| CL2007002567A1 (es) | 2006-09-08 | 2008-02-01 | Amgen Inc | Proteinas aisladas de enlace a activina a humana. |
| CN100586476C (zh) * | 2006-10-13 | 2010-02-03 | 中国人民解放军第四军医大学 | 一种Myostatin特异性抗体的治疗性疫苗及其制备方法 |
| TWI454479B (zh) | 2007-03-06 | 2014-10-01 | Amgen Inc | 變異之活動素受體多肽及其用途 |
| PE20091163A1 (es) * | 2007-11-01 | 2009-08-09 | Wyeth Corp | Anticuerpos para gdf8 |
| PE20090982A1 (es) | 2007-11-05 | 2009-08-13 | Novartis Ag | Derivados de piperidina como inhibidores de la proteina de transferencia de colesteril-ester (cetp) |
| TWI784538B (zh) | 2008-08-14 | 2022-11-21 | 美商艾瑟勒朗法瑪公司 | 使用ｇｄｆ阱以增加紅血球水平 |
| TW201029662A (en) * | 2008-12-19 | 2010-08-16 | Glaxo Group Ltd | Novel antigen binding proteins |
| EP3275900A1 (en) | 2009-04-27 | 2018-01-31 | Novartis AG | Compositions and methods for increasing muscle growth |
| ES2865648T3 (es) | 2009-06-26 | 2021-10-15 | Regeneron Pharma | Anticuerpos biespecíficos fácilmente aislados con formato de inmunoglobulina nativa |
| JO3340B1 (ar) * | 2010-05-26 | 2019-03-13 | Regeneron Pharma | مضادات حيوية لـعامل تمايز النمو 8 البشري |
| AU2012339722B2 (en) | 2011-11-14 | 2017-09-14 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for increasing muscle mass and muscle strength by specifically antagonizing GDF8 and/or Activin A |
| TWI655207B (zh) | 2013-07-30 | 2019-04-01 | 再生元醫藥公司 | 抗活化素ａ之抗體及其用途 |
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