RU2704285C2 - Композиции и способы применения для лечения метаболических расстройств - Google Patents
Композиции и способы применения для лечения метаболических расстройств Download PDFInfo
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- RU2704285C2 RU2704285C2 RU2015136440A RU2015136440A RU2704285C2 RU 2704285 C2 RU2704285 C2 RU 2704285C2 RU 2015136440 A RU2015136440 A RU 2015136440A RU 2015136440 A RU2015136440 A RU 2015136440A RU 2704285 C2 RU2704285 C2 RU 2704285C2
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- C—CHEMISTRY; METALLURGY
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| US201361882542P | 2013-09-25 | 2013-09-25 | |
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| RU2836280C1 (ru) * | 2019-11-26 | 2025-03-12 | Юхан Корпорейшн | Слитый белок gdf15 длительного действия и содержащая его фармацевтическая композиция |
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| CA3026701C (en) | 2009-03-02 | 2023-04-18 | Massachusetts Institute Of Technology | Methods and products for in vivo enzyme profiling |
| WO2012125808A1 (en) | 2011-03-15 | 2012-09-20 | Massachusetts Institute Of Technology | Multiplexed detection with isotope-coded reporters |
| MX2014009129A (es) | 2012-01-26 | 2014-11-21 | Amgen Inc | Polipeptidos de factor 15 de diferenciacion de crecimiento (gdf-15). |
| CA2862516C (en) | 2012-03-27 | 2023-02-14 | Ngm Biopharmaceuticals, Inc. | Compositions and methods of use for treating metabolic disorders |
| WO2014120619A2 (en) | 2013-01-30 | 2014-08-07 | Ngm Biopharmaceuticals, Inc. | Compositions and methods of use in treating metabolic disorders |
| US9161966B2 (en) | 2013-01-30 | 2015-10-20 | Ngm Biopharmaceuticals, Inc. | GDF15 mutein polypeptides |
| WO2014197840A1 (en) | 2013-06-07 | 2014-12-11 | Massachusetts Institute Of Technology | Affinity-based detection of ligand-encoded synthetic biomarkers |
| EA037355B1 (ru) * | 2013-07-31 | 2021-03-17 | Эмджен Инк. | Конструкции на основе фактора дифференцировки и роста 15 (gdf-15) |
| US20170204149A1 (en) * | 2014-06-23 | 2017-07-20 | Novartis Ag | Hsa-gdf-15 fusion polypeptide and use thereof |
| ES2818109T3 (es) * | 2014-06-23 | 2021-04-09 | Novartis Ag | Modificaciones de proteínas específicas para un sitio |
| US10588980B2 (en) | 2014-06-23 | 2020-03-17 | Novartis Ag | Fatty acids and their use in conjugation to biomolecules |
| AU2015279525A1 (en) | 2014-06-24 | 2016-12-15 | Novo Nordisk A/S | MIC-1 fusion proteins and uses thereof |
| UA123432C2 (uk) | 2014-07-30 | 2021-04-07 | Нджм Біофармасьютікалз, Інк. | Димер та спосіб його застосування для лікування метаболічних розладів |
| EP3922259A1 (en) * | 2014-10-30 | 2021-12-15 | Acceleron Pharma Inc. | Methods and compositions using gdf15 polypeptides for increasing red blood cells |
| ES2799503T3 (es) * | 2014-10-31 | 2020-12-18 | Ngm Biopharmaceuticals Inc | Composiciones y procedimientos de uso para el tratamiento de trastornos metabólicos |
| EP3237440A1 (en) * | 2014-12-22 | 2017-11-01 | Novo Nordisk A/S | Alpha-1-antitrypsin (a1at) fusion proteins and uses thereof |
| CN108463244B (zh) | 2015-08-04 | 2022-05-27 | 杜克大学 | 用于递送的基因编码的固有无序隐形聚合物及其使用方法 |
| US11752213B2 (en) | 2015-12-21 | 2023-09-12 | Duke University | Surfaces having reduced non-specific binding and antigenicity |
| CN108367053A (zh) * | 2015-12-22 | 2018-08-03 | 诺华股份有限公司 | 使用生长分化因子15(gdf-15)治疗或改善代谢性疾病的方法 |
| US11105818B2 (en) | 2016-01-15 | 2021-08-31 | Novo Nordisk A/S | MIC-1 receptor and uses thereof |
| PE20190126A1 (es) | 2016-03-31 | 2019-01-17 | Ngm Biopharmaceuticals Inc | Proteinas de union y metodos de uso de las mismas |
| EP3440013A4 (en) * | 2016-04-08 | 2021-03-17 | Massachusetts Institute of Technology | METHODS FOR SPECIFICALLY PROFILING PROTEASE ACTIVITY AT LYMPHATIC GANGLIONS |
| CA3022928A1 (en) | 2016-05-05 | 2017-11-09 | Massachusetts Institute Of Technology | Methods and uses for remotely triggered protease activity measurements |
| US10336812B2 (en) * | 2016-05-10 | 2019-07-02 | Janssen Biotech, Inc. | GDF15 fusion proteins and uses thereof |
| AU2017269496B2 (en) | 2016-05-24 | 2021-03-25 | Novo Nordisk A/S | MIC-1 compounds and use thereof |
| WO2017210476A1 (en) | 2016-06-01 | 2017-12-07 | Duke University | Nonfouling biosensors |
| CN110023326A (zh) | 2016-09-23 | 2019-07-16 | 杜克大学 | 具有lcst行为的非结构化无重复多肽 |
| US11648200B2 (en) | 2017-01-12 | 2023-05-16 | Duke University | Genetically encoded lipid-polypeptide hybrid biomaterials that exhibit temperature triggered hierarchical self-assembly |
| EP3607085A1 (en) | 2017-04-07 | 2020-02-12 | Massachusetts Institute Of Technology | Methods to spatially profile protease activity in tissue and sections |
| WO2018213320A1 (en) | 2017-05-15 | 2018-11-22 | Duke University | Recombinant production of hybrid lipid-biopolymer materials that self-assemble and encapsulate agents |
| TWI710377B (zh) | 2017-05-23 | 2020-11-21 | 丹麥商諾佛 儂迪克股份有限公司 | Ｍｉｃ－１化合物及其用途 |
| US11680083B2 (en) | 2017-06-30 | 2023-06-20 | Duke University | Order and disorder as a design principle for stimuli-responsive biopolymer networks |
| US11260108B2 (en) | 2017-09-10 | 2022-03-01 | Novo Nordisk A/S | MIC-1 and GLP-1 for use in the treatment of obesity |
| WO2019147954A1 (en) | 2018-01-26 | 2019-08-01 | Duke University | Albumin binding peptide-drug (aibiped) conjugates and methods of making and using same |
| WO2019173332A1 (en) | 2018-03-05 | 2019-09-12 | Massachusetts Institute Of Technology | Inhalable nanosensors with volatile reporters and uses thereof |
| TWI724392B (zh) | 2018-04-06 | 2021-04-11 | 美商美國禮來大藥廠 | 生長分化因子15促效劑化合物及其使用方法 |
| CR20200510A (es) * | 2018-04-09 | 2020-11-26 | Amgen Inc | Protreínas de fusión del factor de diferenciación de crecimiento 15 |
| WO2019213150A1 (en) | 2018-04-30 | 2019-11-07 | Duke University | Stimuli-responsive peg-like polymer-based drug delivery platform |
| WO2020028806A1 (en) | 2018-08-02 | 2020-02-06 | Duke University | Dual agonist fusion proteins |
| CN112543869A (zh) | 2018-08-10 | 2021-03-23 | 诺华股份有限公司 | Gfral细胞外结构域和使用方法 |
| WO2020068920A2 (en) | 2018-09-25 | 2020-04-02 | Massachusetts Institute Of Technology | Lung protease nanosensors and uses thereof |
| CN113226351B (zh) | 2018-10-22 | 2025-01-14 | 詹森药业有限公司 | 胰高血糖素样肽1(glp1)-生长分化因子15(gdf15)融合蛋白及其用途 |
| EP3911753A1 (en) | 2019-01-17 | 2021-11-24 | Massachusetts Institute of Technology | Sensors for detecting and imaging of cancer metastasis |
| AU2020219142B2 (en) * | 2019-02-05 | 2025-11-06 | Syracuse University | Peptide ligands of the GDNF family receptor a-like (GFRAL) receptor |
| MX2021010737A (es) * | 2019-03-08 | 2021-09-28 | Amgen Inc | Terapia de combinacion por factor de diferenciacion del crecimiento 15. |
| KR20200124176A (ko) * | 2019-04-23 | 2020-11-02 | 주식회사 엘지화학 | 면역글로불린의 Fc 영역 및 GDF15를 포함하는 융합 폴리펩타이드 |
| US11512314B2 (en) | 2019-07-12 | 2022-11-29 | Duke University | Amphiphilic polynucleotides |
| EP4041281B1 (en) | 2019-10-04 | 2025-11-26 | Amgen Inc. | Use of gdf15 for treating cardiometabolic syndrome and other conditions |
| MX2022006173A (es) * | 2019-11-26 | 2022-06-14 | Yuhan Corp | Proteinas de fusion gdf15 de accion prolongada y composicion farmaceutica que comprende la misma. |
| US20230093708A1 (en) * | 2020-03-04 | 2023-03-23 | Duke University | Protein nanoparticle design and application |
| EP4237438A4 (en) * | 2020-10-27 | 2024-11-27 | Beijing QL Biopharmaceutical Co., Ltd. | GDF15 FUSION PROTEINS AND THEIR USE |
| WO2022219495A1 (en) | 2021-04-12 | 2022-10-20 | Novartis Ag | 2-((4-((s)-2-(4-chloro-2-fluorophenyl)-2-methylbenzo[d][1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((s)-oxetan-2-yl)methyl)-1h-imidazole derivatives as activators of the glp1 receptor for the treatment of obesity |
| TW202342014A (zh) | 2022-02-10 | 2023-11-01 | 瑞士商諾華公司 | １，３－苯并二氧戊環衍生物 |
| WO2023154953A1 (en) | 2022-02-14 | 2023-08-17 | Ngm Biopharmaceuticals, Inc. | Gdf15 polypeptides for treating and preventing autoimmune diseases |
Family Cites Families (92)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5194596A (en) | 1989-07-27 | 1993-03-16 | California Biotechnology Inc. | Production of vascular endothelial cell growth factor |
| FR2650598B1 (fr) | 1989-08-03 | 1994-06-03 | Rhone Poulenc Sante | Derives de l'albumine a fonction therapeutique |
| US5350836A (en) | 1989-10-12 | 1994-09-27 | Ohio University | Growth hormone antagonists |
| FR2686899B1 (fr) | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
| WO1994003599A1 (fr) | 1992-08-04 | 1994-02-17 | Sagami Chemical Research Center | ADNc HUMAIN ET PROTEINE POUR LAQUELLE CODE CET ADNc |
| US6180602B1 (en) | 1992-08-04 | 2001-01-30 | Sagami Chemical Research Center | Human novel cDNA, TGF-beta superfamily protein encoded thereby and the use of immunosuppressive agent |
| JPH07250688A (ja) | 1994-01-28 | 1995-10-03 | Sagami Chem Res Center | ＴＧＦ−βスーパーファミリー蛋白質をコードするヒト新規ｃＤＮＡ |
| JPH07258293A (ja) * | 1994-03-23 | 1995-10-09 | Asahi Chem Ind Co Ltd | 新規な蛋白質ならびにその製造方法 |
| WO1996018730A1 (en) | 1994-12-15 | 1996-06-20 | Human Genome Sciences, Inc. | Prostatic growth factor |
| US6521227B1 (en) * | 1999-11-18 | 2003-02-18 | Peter L. Hudson | Polynucleotides encoding prostatic growth factor and process for producing prostatic growth factor polypeptides |
| US5994102A (en) | 1994-12-15 | 1999-11-30 | Human Genome Sciences, Inc. | Polynucleotides encoding prostatic growth factor and process for producing prostatic growth factor polypeptides |
| ES2324433T3 (es) | 1995-06-22 | 2009-08-06 | St Vincent's Hospital Sydney Limited | Tgf-beta novedoso similar a citocina. |
| US6524802B1 (en) | 1996-03-29 | 2003-02-25 | The Johns Hopkins University School Of Medicine | Methods of detecting growth differentiation factor-14 |
| BR9711763A (pt) * | 1996-09-11 | 1999-08-24 | Ortho Mcneil Pharm Inc | Prote¡na semelhante a tnf-beta para tratamento do cÆncer de prÄstata e mol-cula de acido nucleico composi-oes farmaceutica e processos correlatos |
| WO1999006445A1 (en) | 1997-07-31 | 1999-02-11 | The Johns Hopkins University School Of Medicine | Growth differentiation factor-15 |
| JP2003526322A (ja) | 1998-07-23 | 2003-09-09 | スミスクライン ビーチャム コーポレーション | 分泌型システインリッチタンパク質−６（ｓｃｒｐ−６） |
| US6465181B2 (en) | 1999-03-25 | 2002-10-15 | Abbott Laboratories | Reagents and methods useful for detecting diseases of the prostate |
| US6974684B2 (en) | 2001-08-08 | 2005-12-13 | Curagen Corporation | Therapeutic polypeptides, nucleic acids encoding same, and methods of use |
| DE60032355T2 (de) | 1999-05-17 | 2007-04-26 | Biopharm Gesellschaft Zur Biotechnologischen Entwicklung Und Zum Vertrieb Von Pharmaka Mbh | NEUROPROTEKTIVE EIGENSCHAFTEN VON GDF-15, EINEM VERTRETER DER TGF-ß-SUPERFAMILIE |
| ES2529300T3 (es) | 2000-04-12 | 2015-02-18 | Novozymes Biopharma Dk A/S | Proteínas de fusión de albúmina |
| CA2405680C (en) | 2000-04-20 | 2018-02-13 | St. Vincent's Hospital Sydney Limited | Diagnostic assay and method of treatment involving macrophage inhibitory cytokine -1 (mic-1) |
| WO2002020759A2 (en) | 2000-09-08 | 2002-03-14 | The Government Of The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | A non-steroidal anti-inflammatory drug activated gene with anti-tumorigenic properties |
| WO2002062999A2 (en) | 2000-12-29 | 2002-08-15 | Curagen Corporation | Proteins and nucleic acids encoding same |
| TW200526779A (en) | 2001-02-08 | 2005-08-16 | Wyeth Corp | Modified and stabilized GDF propeptides and uses thereof |
| US7511121B2 (en) | 2001-03-09 | 2009-03-31 | Arnason Barry G W | Polymeric immunoglobulin fusion proteins that target low-affinity Fcγreceptors |
| NZ542878A (en) | 2001-05-11 | 2007-06-29 | Amgen Inc | Peptides and related molecules that bind to tall-1 in particular SEQ ID NO:104 |
| US20030053431A1 (en) | 2001-09-10 | 2003-03-20 | Lila Madour | Method for performing handoff in a radio telecommunications network |
| US20060253913A1 (en) | 2001-12-21 | 2006-11-09 | Yue-Jin Huang | Production of hSA-linked butyrylcholinesterases in transgenic mammals |
| WO2003060071A2 (en) | 2001-12-21 | 2003-07-24 | Human Genome Sciences, Inc. | Albumin fusion proteins |
| US7919084B2 (en) | 2002-06-17 | 2011-04-05 | St. Vincent's Hospital Sydney Limited | Methods of diagnosis, prognosis and treatment of cardiovascular disease |
| CA2390820A1 (en) | 2002-06-17 | 2003-12-17 | St. Vincent's Hospital Sydney Limited | Methods of diagnosis, prognosis and treatment of cardiovascular disease |
| CN1241946C (zh) | 2002-07-01 | 2006-02-15 | 美国福源集团 | 对多种细胞具刺激增生作用的人血清白蛋白重组融合蛋白 |
| CA2504508A1 (en) | 2002-11-08 | 2004-05-27 | Barnes-Jewish Hospital | Methods and compositions for prostate epithelial cell differentiation |
| US7348004B2 (en) | 2003-05-06 | 2008-03-25 | Syntonix Pharmaceuticals, Inc. | Immunoglobulin chimeric monomer-dimer hybrids |
| SI2441466T1 (sl) | 2004-04-13 | 2015-01-30 | St Vincent's Hospital Sydney Limited Centre For Immunology | Sredstvo, ki inhibira MIC-1 |
| WO2005113585A2 (en) | 2004-05-20 | 2005-12-01 | Acceleron Pharma Inc. | Modified tgf-beta superfamily polypeptides |
| US7670595B2 (en) | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
| PL1844337T3 (pl) | 2005-01-24 | 2013-12-31 | Pepscan Systems Bv | Związki wiążące, związki immunogenne i peptydomimetyki |
| JP2007258293A (ja) | 2006-03-22 | 2007-10-04 | Fuji Electric Holdings Co Ltd | はんだ濡れ性評価装置およびはんだ濡れ性評価方法 |
| EP2004683B1 (en) | 2006-03-24 | 2016-05-11 | Biogen Hemophilia Inc. | Pc5 as a factor ix propeptide processing enzyme |
| US8974748B2 (en) | 2007-04-05 | 2015-03-10 | Corning Incorporated | Dual inlet microchannel device and method for using same |
| US7754689B2 (en) | 2006-06-02 | 2010-07-13 | Wyeth Llc | Finger-1 peptide analogs of the TGF-β superfamily |
| BRPI0712496A2 (pt) | 2006-06-02 | 2012-09-25 | Wyeth Corp | peptìdeo isolado, composição compreendendo o referido peptìdeo, ácido nucléico isolado e métodos de purificar uma proteìna na superfamìlia do fator beta de transformação do crescimento (tgf-?) e de estabilizar uma solução contendo uma proteìna na superfamìlia tgf-b. |
| NZ574423A (en) * | 2006-07-26 | 2012-04-27 | Pepscan Systems Bv | Immunogenic compounds and protein mimics |
| JP5309026B2 (ja) | 2006-08-04 | 2013-10-09 | メディツィニッシュ ホホシュール ハノーバー | Ｇｄｆ−１５に基づく心臓インターベンションの危険性を評価するための手段および方法 |
| CN101808672B (zh) | 2007-04-25 | 2013-05-01 | 干细胞旋转股份公司 | 干细胞系、其应用以及培养方法 |
| CA2720628A1 (en) | 2007-07-26 | 2009-01-29 | Novagen Holding Corporation | Fusion proteins having mutated immunoglobulin hinge region |
| JP2010536717A (ja) | 2007-08-16 | 2010-12-02 | セントビンセンツ ホスピタル シドニー リミテッド | マクロファージ阻害性サイトカイン（ｍｉｃ−１）活性を調節するための作用物質及び方法 |
| WO2009046495A1 (en) | 2007-10-09 | 2009-04-16 | St Vincent's Hospital Sydney Limited | A method of treating cachexia with the removal or inactivation of macrophage inhibitory cytokine-1 |
| US20110039284A1 (en) | 2007-10-22 | 2011-02-17 | Samuel Norbert Breit | Methods of prognosis |
| SI2235064T1 (sl) | 2008-01-07 | 2016-04-29 | Amgen Inc. | Metoda za izdelavo heterodimernih molekul - protitelesa fc z uporabo elektrostatičnih usmerjevalnih učinkov |
| EP2227696A1 (en) | 2008-01-08 | 2010-09-15 | Roche Diagnostics GmbH | Means and methods for assessing the risk of patients presenting to emergency units based on gdf-15 |
| CN102037004A (zh) | 2008-01-08 | 2011-04-27 | 生物种属学股份公司 | 使用寡糖基转移酶的多肽的糖缀合 |
| WO2009141357A1 (en) | 2008-05-20 | 2009-11-26 | Roche Diagnostics Gmbh | Gdf-15 as biomarker in type 1 diabetes |
| EP2318844A1 (en) | 2008-07-14 | 2011-05-11 | Roche Diagnostics GmbH | Multimarker panel for diagnosing, monitoring and selecting the therapy for patients with heart failure |
| WO2010019263A2 (en) | 2008-08-15 | 2010-02-18 | Genzyme Corporation | Soluble flt constructs for treating cancers |
| EP2350669B9 (en) | 2008-10-31 | 2014-06-11 | St Vincent's Hospital Sydney Limited | Methods of prognosis in chronic kidney disease |
| ES2727950T3 (es) | 2008-10-31 | 2019-10-21 | Janssen Biotech Inc | Diferenciación de células madre embrionarias humanas en linaje endocrino pancreático |
| EP2211182A1 (en) | 2009-01-16 | 2010-07-28 | Roche Diagnostics GmbH | Method for the assessment of severity of liver cirrhosis |
| EP2209003A1 (en) | 2009-01-16 | 2010-07-21 | F. Hoffmann-Roche AG | Means and methods for differentiating between fibrosis and cirrhosis |
| US20100204123A1 (en) | 2009-02-12 | 2010-08-12 | Mary Elizabeth Pecquet Goad | Peripheral Administration of Proteins Including TGF-beta Superfamily Members for Treatment of Systemic Disorders and Disease |
| GB0902737D0 (en) | 2009-02-19 | 2009-04-01 | Univ Gent | GDF15 as a differential marker for spondyloarthropathy |
| US8952130B2 (en) * | 2009-02-24 | 2015-02-10 | The Salk Institute For Biological Studies | Designer ligands of TGF-β superfamily |
| DK3248610T5 (da) * | 2009-05-05 | 2024-10-07 | Amgen Inc | Fgf21-mutanter og anvendelser deraf |
| CA2766166A1 (en) | 2009-07-08 | 2011-01-13 | Amgen Inc. | Design of stable and aggregation free antibody fc molecules through ch3 domain interface engineering |
| WO2011008956A2 (en) | 2009-07-15 | 2011-01-20 | Zirus, Inc. | Mammalian genes involved in infection |
| US20120309697A1 (en) | 2009-10-28 | 2012-12-06 | Samuel Norbert Breit | Methods of diagnosing and prognosing colonic polyps |
| ES2636971T3 (es) | 2009-11-05 | 2017-10-10 | F. Hoffmann-La Roche Ag | Procedimientos y composición para la secreción de polipéptidos heterógenos |
| WO2011064758A2 (en) | 2009-11-30 | 2011-06-03 | Pfizer Limited | Fusion protein |
| US9212221B2 (en) | 2010-03-03 | 2015-12-15 | Detroit R & D, Inc. | Form-specific antibodies for NAG-1 (MIC-1, GDF-15), H6D and other TGF-β subfamily and heart disease and cancer diagnoses |
| JP5791335B2 (ja) | 2010-04-07 | 2015-10-07 | 花王株式会社 | オルガノポリシロキサン化合物の製造方法 |
| US20130202564A1 (en) | 2010-04-09 | 2013-08-08 | University Of Southern California | Systems and Methods of Cell Activated, Controlled Release Delivery of Growth Factors for Tissue Repair and Regeneration |
| EP2383571A1 (en) | 2010-05-02 | 2011-11-02 | Prof. Hess Medical Consulting GmbH | Growth differntioation factor 15 (GDF 15) for risk prediction of diabetic foot ulcer |
| CN105044349B (zh) | 2010-08-26 | 2018-04-06 | 弗·哈夫曼-拉罗切有限公司 | 生物标志物在评估从动脉高血压向心力衰竭的早期转变中的用途 |
| EP2439535A1 (en) | 2010-10-07 | 2012-04-11 | F. Hoffmann-La Roche AG | Diagnosis of diabetes related heart disease and GDF-15 and Troponin as predictors for the development of type 2 diabetes mellitus |
| US10752664B2 (en) | 2011-04-08 | 2020-08-25 | Amgen Inc. | Method of treating or ameliorating metabolic disorders using growth differentiation factor 15 (GDF-15) |
| SMT201700025T1 (it) | 2011-04-13 | 2017-03-08 | Bristol Myers Squibb Co | Proteine di fusione ad fc comprendenti nuovi raccordi o arrangiamenti |
| AU2012275233A1 (en) | 2011-06-30 | 2013-11-28 | Genentech, Inc. | Anti-c-met antibody formulations |
| EP4011913A1 (en) | 2011-06-30 | 2022-06-15 | Chugai Seiyaku Kabushiki Kaisha | Heterodimerized polypeptide |
| MX2014009129A (es) | 2012-01-26 | 2014-11-21 | Amgen Inc | Polipeptidos de factor 15 de diferenciacion de crecimiento (gdf-15). |
| CA2862516C (en) * | 2012-03-27 | 2023-02-14 | Ngm Biopharmaceuticals, Inc. | Compositions and methods of use for treating metabolic disorders |
| ES2784223T3 (es) | 2012-06-20 | 2020-09-23 | Univ Virginia Patent Foundation | Composiciones y procedimientos para regular la homeostasis de glucosa y la acción de insulina |
| WO2014000042A1 (en) | 2012-06-27 | 2014-01-03 | Prince Henry's Institute Of Medical Research | COMPOSITIONS AND METHODS FOR MODIFYING TGF-β FAMILY LIGANDS |
| US9346872B2 (en) | 2012-08-08 | 2016-05-24 | Roche Glycart Ag | Interleukin-10 fusion proteins |
| EP2934584B1 (en) | 2012-12-21 | 2020-02-19 | Aveo Pharmaceuticals, Inc. | Anti-gdf15 antibodies |
| WO2014120619A2 (en) | 2013-01-30 | 2014-08-07 | Ngm Biopharmaceuticals, Inc. | Compositions and methods of use in treating metabolic disorders |
| US9161966B2 (en) | 2013-01-30 | 2015-10-20 | Ngm Biopharmaceuticals, Inc. | GDF15 mutein polypeptides |
| RS57393B1 (sr) | 2013-03-15 | 2018-09-28 | Hoffmann La Roche | Il-22 polipeptiidi i il-22 fuzioni proteini i metode za njihovu upotrebu |
| CA2919076C (en) | 2013-07-31 | 2024-01-30 | Amgen Inc. | Stabilization of fc-containing polypeptides |
| EA037355B1 (ru) | 2013-07-31 | 2021-03-17 | Эмджен Инк. | Конструкции на основе фактора дифференцировки и роста 15 (gdf-15) |
| UA123432C2 (uk) | 2014-07-30 | 2021-04-07 | Нджм Біофармасьютікалз, Інк. | Димер та спосіб його застосування для лікування метаболічних розладів |
| ES2799503T3 (es) | 2014-10-31 | 2020-12-18 | Ngm Biopharmaceuticals Inc | Composiciones y procedimientos de uso para el tratamiento de trastornos metabólicos |
-
2014
- 2014-01-27 WO PCT/US2014/013232 patent/WO2014120619A2/en not_active Ceased
- 2014-01-27 US US14/763,262 patent/US9828415B2/en active Active
- 2014-01-27 BR BR112015018104A patent/BR112015018104A2/pt not_active IP Right Cessation
- 2014-01-27 CA CA2899170A patent/CA2899170C/en active Active
- 2014-01-27 AU AU2014212640A patent/AU2014212640B2/en not_active Ceased
- 2014-01-27 JP JP2015555389A patent/JP6272907B2/ja not_active Expired - Fee Related
- 2014-01-27 EP EP14746188.3A patent/EP2950807B1/en not_active Not-in-force
- 2014-01-27 RU RU2015136440A patent/RU2704285C2/ru active
- 2014-01-27 KR KR1020157023041A patent/KR101993714B1/ko not_active Expired - Fee Related
-
2017
- 2017-10-20 US US15/789,679 patent/US10323075B2/en active Active
-
2019
- 2019-04-29 US US16/397,578 patent/US20200087366A1/en not_active Abandoned
-
2021
- 2021-05-26 US US17/330,984 patent/US20210388047A1/en not_active Abandoned
Non-Patent Citations (6)
| Title |
|---|
| BAUSKIN A. R. et al., The TGF-β superfamily cytokine MIC-1/GDF15: secretory mechanisms facilitate creation of latent stromal stores, Journal of Interferon & Cytokine Research, 2010, V. 30, N. 6, p. 389-397. * |
| BOOTCOV M. R. et al., MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-β superfamily, Proceedings of the National Academy of Sciences, 1997, V. 94, N. 21, p. 11514-11519. * |
| JOHNEN H. et al., Tumor-induced anorexia and weight loss are mediated by the TGF-β superfamily cytokine MIC-1, Nature medicine, 2007, V. 13, N. 11, p. 1333-1340. * |
| JOHNEN H. et al., Tumor-induced anorexia and weight loss are mediated by the TGF-β superfamily cytokine MIC-1, Nature medicine, 2007, V. 13, N. 11, p. 1333-1340. MACIA L. et al., Macrophage inhibitory cytokine 1 (MIC-1/GDF15) decreases food intake, body weight and improves glucose tolerance in mice on normal & obesogenic diets, PloS one, 2012, V. 7, N. 4, p. e34868. BAUSKIN A. R. et al., The TGF-β superfamily cytokine MIC-1/GDF15: secretory mechanisms facilitate creation of latent stromal stores, Journal of Interferon & Cytokine Research, 2010, V. 30, N. 6, p. 389-397. BOOTCOV M. R. et al., MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-β superfamily, Proceedings of the National Academy of Sciences, 1997, V. 94, N. 21, p. 11514-11519. КНОРРЕ Д. Г. и др., Химические и функциональные аспекты посттрансляционной модификации белков, Acta Naturae, 2009, V. 1, N. 3, с.32-56. * |
| MACIA L. et al., Macrophage inhibitory cytokine 1 (MIC-1/GDF15) decreases food intake, body weight and improves glucose tolerance in mice on normal & obesogenic diets, PloS one, 2012, V. 7, N. 4, p. e34868. * |
| КНОРРЕ Д. Г. и др., Химические и функциональные аспекты посттрансляционной модификации белков, Acta Naturae, 2009, V. 1, N. 3, с.32-56. * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2836280C1 (ru) * | 2019-11-26 | 2025-03-12 | Юхан Корпорейшн | Слитый белок gdf15 длительного действия и содержащая его фармацевтическая композиция |
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| EP2950807B1 (en) | 2018-03-28 |
| JP2016511752A (ja) | 2016-04-21 |
| EP2950807A2 (en) | 2015-12-09 |
| HK1211497A1 (en) | 2016-05-27 |
| CA2899170C (en) | 2022-08-02 |
| US10323075B2 (en) | 2019-06-18 |
| BR112015018104A2 (pt) | 2017-11-21 |
| AU2014212640B2 (en) | 2017-10-19 |
| WO2014120619A2 (en) | 2014-08-07 |
| KR20150114512A (ko) | 2015-10-12 |
| US20210388047A1 (en) | 2021-12-16 |
| US20200087366A1 (en) | 2020-03-19 |
| WO2014120619A3 (en) | 2014-09-25 |
| US20180100003A1 (en) | 2018-04-12 |
| JP6272907B2 (ja) | 2018-01-31 |
| KR101993714B1 (ko) | 2019-06-28 |
| CA2899170A1 (en) | 2014-08-07 |
| RU2015136440A (ru) | 2018-12-25 |
| EP2950807A4 (en) | 2016-11-02 |
| US9828415B2 (en) | 2017-11-28 |
| AU2014212640A1 (en) | 2015-08-13 |
| US20160200787A1 (en) | 2016-07-14 |
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