TW201625288A - 使用ａｃｔｒｉｉ配位體捕捉以治療心血管疾病 - Google Patents
使用ａｃｔｒｉｉ配位體捕捉以治療心血管疾病 Download PDFInfo
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| CA2161807A1 (en) | 1993-05-12 | 1994-11-24 | Anthony J. Celeste | Bmp-10 compositions |
| US5637480A (en) | 1993-05-12 | 1997-06-10 | Genetics Institute, Inc. | DNA molecules encoding bone morphogenetic protein-10 |
| US5677196A (en) | 1993-05-18 | 1997-10-14 | University Of Utah Research Foundation | Apparatus and methods for multi-analyte homogeneous fluoro-immunoassays |
| US5831050A (en) | 1993-06-07 | 1998-11-03 | Creative Biomolecules, Inc. | Morphogen cell surface receptor |
| ATE355369T1 (de) | 1993-10-14 | 2006-03-15 | Harvard College | Verfahren zur induzierung und zur erhaltung neuronalen zellen |
| US5525490A (en) | 1994-03-29 | 1996-06-11 | Onyx Pharmaceuticals, Inc. | Reverse two-hybrid method |
| US5658876A (en) | 1994-04-28 | 1997-08-19 | The General Hospital Corporation | Activin antagonists as novel contraceptives |
| US5760010A (en) | 1995-01-01 | 1998-06-02 | Klein; Ira | Method of treating liver disorders with a macrolide antibiotic |
| US5814565A (en) | 1995-02-23 | 1998-09-29 | University Of Utah Research Foundation | Integrated optic waveguide immunosensor |
| NZ306767A (en) | 1995-04-11 | 2000-03-27 | Univ Johns Hopkins | Method of identifying molecular interactions employing counterselection and at least two hybrid molecules or two hybrid systems |
| EP0771873A3 (en) | 1995-10-27 | 1998-03-04 | Takeda Chemical Industries, Ltd. | Neuronal cell-specific receptor protein |
| GB9526131D0 (en) | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Recombinant chimeric receptors |
| US20050244867A1 (en) | 1996-03-26 | 2005-11-03 | Human Genome Sciences, Inc. | Growth factor HTTER36 |
| US6004780A (en) | 1996-03-26 | 1999-12-21 | Human Genome Sciences, Inc. | Growth factor HTTER36 |
| AU721196B2 (en) | 1996-10-25 | 2000-06-29 | G.D. Searle & Co. | Circularly permuted erythropoietin receptor agonists |
| US6605699B1 (en) | 1997-01-21 | 2003-08-12 | Human Genome Sciences, Inc. | Galectin-11 polypeptides |
| US6231880B1 (en) | 1997-05-30 | 2001-05-15 | Susan P. Perrine | Compositions and administration of compositions for the treatment of blood disorders |
| 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 |
| US6696260B1 (en) | 1997-08-01 | 2004-02-24 | The Johns Hopkins University School Of Medicine | Methods to identify growth differentiation factor (GDF) binding proteins |
| AU8666398A (en) | 1997-08-01 | 1999-02-22 | Johns Hopkins University School Of Medicine, The | Methods to identify growth differentiation factor (gdf) receptors |
| US6953662B2 (en) | 1997-08-29 | 2005-10-11 | Human Genome Sciences, Inc. | Follistatin-3 |
| EP1015468A4 (en) | 1997-08-29 | 2000-09-06 | Human Genome Sciences Inc | FOLLISTATINE-3 |
| US6696411B1 (en) | 1998-04-22 | 2004-02-24 | Cornell Research Foundation, Inc. | Canine erythropoietin gene and recombinant protein |
| JP2002524514A (ja) | 1998-09-17 | 2002-08-06 | イーライ・リリー・アンド・カンパニー | タンパク質製剤 |
| AU5502799A (en) | 1998-09-22 | 2000-04-10 | Long Yu | New human growth differentiation factor encoding sequence and polypeptide encoded by such dna sequence and producing method thereof |
| US6472179B2 (en) | 1998-09-25 | 2002-10-29 | Regeneron Pharmaceuticals, Inc. | Receptor based antagonists and methods of making and using |
| US6548634B1 (en) | 1998-09-30 | 2003-04-15 | Chiron Corporation | Synthetic peptides having FGF receptor affinity |
| US6777205B1 (en) | 1998-11-06 | 2004-08-17 | Sterrenbeld Biotechnologie North America, Inc. | Host cells expressing recombinant human erythropoietin |
| US20040009535A1 (en) | 1998-11-27 | 2004-01-15 | Celltech R&D, Inc. | Compositions and methods for increasing bone mineralization |
| EP1147413B1 (en) | 1999-01-21 | 2006-04-05 | Metamorphix, Inc. | Growth differentiation factor inhibitors and uses therefor |
| CA2365449A1 (en) | 1999-04-19 | 2000-10-26 | Kyowa Hakko Kogyo Co., Ltd. | Inhibitor of the growth of androgen-independent tumor |
| US6468543B1 (en) | 1999-05-03 | 2002-10-22 | Zymogenetics, Inc. | Methods for promoting growth of bone using ZVEGF4 |
| ES2296634T3 (es) | 1999-07-04 | 2008-05-01 | Cardiovascular Research Institute Of Maastricht (Carim) | Ensayo de diagnostico para proteina gla de matriz humana y su utilizacion como biomarcador. |
| IL149267A0 (en) | 1999-11-12 | 2002-11-10 | Maxygen Holdings Ltd | Interferon gamma conjugates |
| KR100791797B1 (ko) | 1999-12-15 | 2008-01-04 | 리서치 디벨럽먼트 파운데이션 | 인히빈 수용체로서의 베타글리칸 및 이의 용도 |
| JP4487376B2 (ja) | 2000-03-31 | 2010-06-23 | 味の素株式会社 | 腎疾患治療剤 |
| US6627424B1 (en) | 2000-05-26 | 2003-09-30 | Mj Bioworks, Inc. | Nucleic acid modifying enzymes |
| AU2001269709A1 (en) | 2000-07-19 | 2002-02-05 | Eli Lilly And Company | Nucleic acids, vectors, host cells, polypeptides, and uses thereof |
| US6632180B1 (en) | 2000-09-07 | 2003-10-14 | John H. Laragh | Method for evaluating and treating hypertension |
| DE10045591A1 (de) | 2000-09-15 | 2002-04-04 | Klaus Pfizenmaier | Ortsspezifische, antikörpervermittelte Aktivierung proapoptotischer Zytokine - AMAIZe (Antibody-Mediated Apoptosis Inducing Zytokine) |
| AU1325102A (en) | 2000-10-16 | 2002-04-29 | Phylos Inc | Protein scaffolds for antibody mimics and other binding proteins |
| US7087224B2 (en) | 2000-10-31 | 2006-08-08 | Amgen Inc. | Method of treating anemia by administering IL-1ra |
| BR0115475A (pt) | 2000-11-20 | 2004-02-10 | Univ Illinois | Proteìnas de estruturação de membranas |
| US20030082233A1 (en) | 2000-12-01 | 2003-05-01 | Lyons Karen M. | Method and composition for modulating bone growth |
| WO2002043759A2 (en) | 2000-12-01 | 2002-06-06 | Wyeth | Method and composition for modulating bone growth |
| US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
| US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
| TW200526779A (en) | 2001-02-08 | 2005-08-16 | Wyeth Corp | Modified and stabilized GDF propeptides and uses thereof |
| US20040132675A1 (en) | 2002-02-08 | 2004-07-08 | Calvin Kuo | Method for treating cancer and increasing hematocrit levels |
| US7294472B2 (en) | 2001-03-14 | 2007-11-13 | Caden Biosciences | Method for identifying modulators of G protein coupled receptor signaling |
| EP1369130A1 (en) | 2001-03-16 | 2003-12-10 | Takeda Chemical Industries, Ltd. | Process for producing sustained release preparation |
| AU2002256371B2 (en) | 2001-04-26 | 2008-01-10 | Amgen Mountain View Inc. | Combinatorial libraries of monomer domains |
| KR101021124B1 (ko) | 2001-05-24 | 2011-03-14 | 지모제넥틱스, 인코포레이티드 | Ｔａｃｉ-면역글로불린 융합 단백질 |
| WO2002094864A2 (en) | 2001-05-25 | 2002-11-28 | Genset S.A. | Human cdnas and proteins and uses thereof |
| AUPR638101A0 (en) | 2001-07-13 | 2001-08-09 | Bioa Pty Limited | Composition and method for treatment of disease |
| JP3888998B2 (ja) | 2001-07-17 | 2007-03-07 | 帝人株式会社 | ＰＰＡＲδ活性化作用を測定することを特徴とする物質の選択方法及び薬剤 |
| US6855344B2 (en) | 2001-07-17 | 2005-02-15 | Integrated Chinese Medicine Holdings, Ltd. | Compositions and methods for prostate and kidney health and disorders, an herbal preparation |
| KR100453877B1 (ko) | 2001-07-26 | 2004-10-20 | 메덱스젠 주식회사 | 연쇄체화에 의한 면역 글로블린 융합 단백질의 제조 방법 및 이 방법에 의해 제조된 ＴＮＦＲ/Ｆｃ 융합 단백질, 상기 단백질을 코딩하는 ＤＮＡ, 상기 ＤＮＡ를 포함하는벡터, 및 상기 벡터에 의한 형질전환체 |
| US7320789B2 (en) | 2001-09-26 | 2008-01-22 | Wyeth | Antibody inhibitors of GDF-8 and uses thereof |
| US6784154B2 (en) | 2001-11-01 | 2004-08-31 | University Of Utah Research Foundation | Method of use of erythropoietin to treat ischemic acute renal failure |
| US20030144203A1 (en) | 2001-12-19 | 2003-07-31 | Voyager Pharmaceutical Corporation | Methods for slowing senescence and treating and preventing diseases associated with senescence |
| US6998118B2 (en) | 2001-12-21 | 2006-02-14 | The Salk Institute For Biological Studies | Targeted retrograde gene delivery for neuronal protection |
| WO2003068801A2 (en) | 2002-02-11 | 2003-08-21 | Genentech, Inc. | Antibody variants with faster antigen association rates |
| AU2003217612A1 (en) | 2002-02-21 | 2003-09-09 | Wyeth | GASP1: a follistatin domain containing protein |
| US20030219846A1 (en) | 2002-02-28 | 2003-11-27 | Pfizer Inc. | Assay for activity of the ActRIIB kinase |
| WO2003087162A2 (en) | 2002-04-18 | 2003-10-23 | Mtm Laboratories Ag | Neopeptides and methods useful for detection and treatment of cancer |
| MXPA05001694A (es) | 2002-08-16 | 2005-07-22 | Wyeth Corp | Elementos de respuesta al estrogeno de bmp-2 y metodos de uso de los mismos. |
| AR047392A1 (es) | 2002-10-22 | 2006-01-18 | Wyeth Corp | Neutralizacion de anticuerpos contra gdf 8 y su uso para tales fines |
| US20040223966A1 (en) | 2002-10-25 | 2004-11-11 | Wolfman Neil M. | ActRIIB fusion polypeptides and uses therefor |
| AU2002953327A0 (en) | 2002-12-12 | 2003-01-09 | Monash University | Methods of diagnosing prognosing and treating activin associated diseases and conditions |
| ATE419846T1 (de) | 2003-02-07 | 2009-01-15 | Prometic Biosciences Inc | Fettsäuren mittlerer kettenlänge, glyceride und analoga als stimulatoren der erythropoiese |
| US20040197828A1 (en) | 2003-03-26 | 2004-10-07 | Gaddy Dana P. | Method for diagnosis and treatment of bone turnover |
| US20070184052A1 (en) | 2003-05-09 | 2007-08-09 | Lin Herbert Y | Soluble tgf-b type III receptor fusion proteins |
| RU2322261C2 (ru) | 2003-06-02 | 2008-04-20 | Уайт | Применение ингибиторов миостатика (gdf8) в сочетании с кортикостероидами для лечения нервно-мышечных заболеваний |
| MEP2808A (xx) | 2003-06-16 | 2010-02-10 | Celltech R & D Inc | Antitijela specifična za sklerositin i metode za povećanje mineralizacije kostiju |
| US7611465B2 (en) | 2003-07-15 | 2009-11-03 | Board Of Regents, The University Of Texas System | Rapid and accurate detection of bone quality using ultrasound critical angle reflectometry |
| WO2005009460A2 (en) | 2003-07-25 | 2005-02-03 | Medexis, S.A. | Pharmaceutical composition comprising activin a, alk-4 or derivatives thereof for the treatment of ophthalmic disorders or cancer |
| DE10335211A1 (de) | 2003-08-01 | 2005-02-17 | Robert Bosch Gmbh | Kraftstoff-Einspritzvorrichtung für eine Brennkraftmaschine |
| WO2005025601A1 (en) | 2003-09-15 | 2005-03-24 | Monash University | Follistatin isoforms and uses thereof |
| US8895540B2 (en) | 2003-11-26 | 2014-11-25 | DePuy Synthes Products, LLC | Local intraosseous administration of bone forming agents and anti-resorptive agents, and devices therefor |
| EP1706428B1 (en) | 2004-01-22 | 2009-09-23 | MERCK PATENT GmbH | Anti-cancer antibodies with reduced complement fixation |
| US20050197292A1 (en) | 2004-01-30 | 2005-09-08 | Glennda Smithson | Compositions and methods for treating T-cell mediated pathological conditions |
| WO2005094871A2 (en) | 2004-03-26 | 2005-10-13 | Acceleron Pharma Inc. | Bmp-3 propeptides and related methods |
| JP2008500816A (ja) | 2004-03-31 | 2008-01-17 | ゼンコー・インコーポレイテッド | 改善された性質を有するｂｍｐ−７変異体 |
| US7741284B2 (en) | 2004-05-12 | 2010-06-22 | Acceleron Pharma Inc. | BMP10 propeptides and related methods |
| AU2005258286A1 (en) | 2004-06-24 | 2006-01-05 | Acceleron Pharma Inc. | GDF3 propeptides and related methods |
| ES2561048T3 (es) | 2004-07-23 | 2016-02-24 | Acceleron Pharma Inc. | Polipéptidos del receptor ActRII |
| US20060034831A1 (en) | 2004-08-12 | 2006-02-16 | Wyeth | Combination therapy for diabetes, obesity and cardiovascular diseases using GDF-8 inhibitors |
| EP1804824B1 (en) | 2004-09-29 | 2017-01-04 | Icahn School of Medicine at Mount Sinai | Fsh and fsh receptor modulator compositions and methods for inhibiting osteoclastic bone resorption and bone loss in osteoporosis |
| CA2587424A1 (en) | 2004-11-16 | 2006-05-26 | Avidia Research Institute | Protein scaffolds and uses thereof |
| NZ538097A (en) | 2005-02-07 | 2006-07-28 | Ovita Ltd | Method and compositions for improving wound healing |
| CA2597925A1 (en) | 2005-02-16 | 2006-08-24 | The General Hospital Corporation | Use of a human hemojuvelin product to regulate hepcidin-mediated iron metabolism |
| KR20080003929A (ko) | 2005-04-26 | 2008-01-08 | 아지노모토 가부시키가이샤 | 골수 적혈구 전구 세포 분화 촉진제 |
| JP2007099764A (ja) | 2005-09-09 | 2007-04-19 | Ajinomoto Co Inc | 血糖低下剤 |
| EA015351B1 (ru) | 2005-09-28 | 2011-06-30 | Займодженетикс, Инк. | Антагонисты il-17a и il-17f и способы их применения |
| JP2009512710A (ja) * | 2005-10-21 | 2009-03-26 | アムジエン・インコーポレーテツド | Ｉｌ−１阻害剤を用いて血管石灰化を抑制する方法 |
| US8067562B2 (en) | 2005-11-01 | 2011-11-29 | Amgen Inc. | Isolated nucleic acid molecule comprising the amino acid sequence of SEQ ID NO:1 |
| US8128933B2 (en) | 2005-11-23 | 2012-03-06 | Acceleron Pharma, Inc. | Method of promoting bone growth by an anti-activin B antibody |
| EP3269381B1 (en) | 2005-11-23 | 2020-10-07 | Acceleron Pharma, Inc. | Activin-actriia antagonists in use for promoting bone growth |
| AU2006321906C1 (en) | 2005-12-06 | 2014-01-16 | Amgen Inc. | Uses of myostatin antagonists |
| JP2009519984A (ja) | 2005-12-20 | 2009-05-21 | メルク フロスト カナダ リミテツド | ステアロイル−補酵素δ−９デサチュラーゼ阻害剤としての芳香族複素環化合物 |
| EP1962835A2 (en) | 2005-12-21 | 2008-09-03 | Schering Corporation | Treatment of nonalcoholic fatty liver disease using cholesterol lowering agents and/or h3 receptor antagonist/inverse agonist |
| EP1973909A2 (en) | 2005-12-22 | 2008-10-01 | Biogen Idec MA Inc. | Transforming growth factor modulators |
| US7361510B2 (en) | 2006-01-20 | 2008-04-22 | Beckman Coulter, Inc. | Methods of detection of iron deficiency |
| EP1976377A4 (en) | 2006-01-25 | 2010-06-23 | Wellstat Therapeutics Corp | COMPOUNDS FOR THE TREATMENT OF METABOLIC DISORDERS |
| MX2008011022A (es) | 2006-02-28 | 2008-09-10 | Wellstat Therapeutics Corp | Compuestos para el tratamiento de trastornos metabolicos. |
| WO2007109668A2 (en) | 2006-03-20 | 2007-09-27 | The Uab Research Foundation | Compositions and methods for improving bone mass through modulation of novel receptors of pth and fragments thereof |
| WO2007120767A2 (en) | 2006-04-14 | 2007-10-25 | Amgen Inc. | Agonist erythropoietin receptor antibodies |
| EA200802213A1 (ru) | 2006-05-09 | 2009-10-30 | Химекуэст Фармасьютикалз, Инк. | Способы лечения заболеваний крови |
| BRPI0714882A2 (pt) | 2006-07-21 | 2013-05-21 | Lyne Lab | composiÇço lÍquida de acetato de cÁlcio e uso de uma soluÇço aquosa que compreende entre cerca de 7% (p/v) e cerca de 21% (p/v) de acetato de cÁlcio |
| GB0615129D0 (en) | 2006-07-29 | 2006-09-06 | Univ Cardiff | Anti-cancer activity of BMP-9 and BMP-10 and their use in cancer therapies |
| WO2008030367A2 (en) | 2006-09-01 | 2008-03-13 | The General Hospital Corporation | Selective myostatin inhibitors |
| CL2007002567A1 (es) | 2006-09-08 | 2008-02-01 | Amgen Inc | Proteinas aisladas de enlace a activina a humana. |
| US7547781B2 (en) | 2006-09-11 | 2009-06-16 | Curis, Inc. | Quinazoline based EGFR inhibitors containing a zinc binding moiety |
| WO2008060139A1 (en) | 2006-11-17 | 2008-05-22 | Erasmus University Medical Center Rotterdam | Methods for controlling mineralization of extracellular matrix, therapeutic methods based thereon and medicaments for use therein |
| WO2008073292A2 (en) | 2006-12-08 | 2008-06-19 | Caritas St. Elizabeth's Medical Center Of Boston, Inc. | Method for protecting renal tubular epithelial cells from radiocontrast nephro parhy (rcn) |
| CN101663322A (zh) | 2006-12-14 | 2010-03-03 | 株式会社未来创药研究所 | 抗紧密连接蛋白3单克隆抗体以及使用该抗体的癌症的治疗和诊断 |
| DK2468290T3 (en) | 2006-12-18 | 2015-06-01 | Acceleron Pharma Inc | Activin-ActRII antagonists for use in the treatment of anemia |
| US8895016B2 (en) * | 2006-12-18 | 2014-11-25 | Acceleron Pharma, Inc. | Antagonists of activin-actriia 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 |
| CN103920139B (zh) | 2007-02-01 | 2018-02-02 | 阿塞勒隆制药公司 | 活化素‑actriia拮抗剂及在治疗或预防乳腺癌中的用途 |
| TW201907946A (zh) | 2007-02-02 | 2019-03-01 | 美商艾瑟勒朗法瑪公司 | 衍生自ＡｃｔＲＩＩＢ的變體與其用途 |
| CA2677605C (en) | 2007-02-09 | 2016-01-19 | Acceleron Pharma Inc. | Activin-actriia antagonists and uses for promoting bone growth in cancer patients |
| TWI454479B (zh) | 2007-03-06 | 2014-10-01 | Amgen Inc | 變異之活動素受體多肽及其用途 |
| CA2685306A1 (en) | 2007-06-01 | 2008-12-11 | Wyeth | Methods and compositions for modulating bmp-10 activity |
| WO2009009059A1 (en) | 2007-07-09 | 2009-01-15 | Biogen Idec Ma Inc. | Spiro compounds as antagonists of tgf-beta |
| TW200911237A (en) | 2007-08-03 | 2009-03-16 | Summit Corp Plc | Drug combinations for the treatment of duchenne muscular dystrophy |
| GB0715087D0 (en) | 2007-08-03 | 2007-09-12 | Summit Corp Plc | Drug combinations for the treatment of duchenne muscular dystrophy |
| GB0715938D0 (en) | 2007-08-15 | 2007-09-26 | Vastox Plc | Method of treatment of duchenne muscular dystrophy |
| WO2009025651A1 (en) | 2007-08-17 | 2009-02-26 | University Of Maine System Board Of Trustees | Biologically active peptide and method of using the same |
| CN101861161B (zh) | 2007-09-18 | 2017-04-19 | 阿塞勒隆制药公司 | 活化素‑actriia拮抗剂和减少或抑制fsh分泌的用途 |
| PE20091163A1 (es) | 2007-11-01 | 2009-08-09 | Wyeth Corp | Anticuerpos para gdf8 |
| KR20100099193A (ko) | 2007-11-21 | 2010-09-10 | 암젠 인크 | Ｗｉｓｅ 결합 항체 및 에피토프 |
| CA2718403A1 (en) | 2008-03-13 | 2009-09-17 | The General Hospital Corporation | Inhibitors of the bmp signaling pathway |
| WO2009137075A1 (en) | 2008-05-06 | 2009-11-12 | Acceleron Pharma Inc. | Anti-activin antibodies and uses for promoting bone growth |
| WO2009137613A2 (en) | 2008-05-06 | 2009-11-12 | Joslin Diabetes Center, Inc. | Methods and compositions for inducing brown adipogenesis |
| CA2729054C (en) | 2008-06-26 | 2019-09-03 | Acceleron Pharma Inc. | Antagonists of actriib and uses for increasing red blood cell levels |
| US20100015144A1 (en) | 2008-06-26 | 2010-01-21 | Acceleron Pharma Inc. | Methods for dosing an activin-actriia antagonist and monitoring of treated patients |
| US8637611B2 (en) | 2008-08-13 | 2014-01-28 | Designer Molecules, Inc. | Amide-extended crosslinking compounds and methods for use thereof |
| PT3494986T (pt) | 2008-08-14 | 2020-07-14 | Acceleron Pharma Inc | Armadilhas para gdf |
| 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 |
| MY159483A (en) | 2008-11-26 | 2017-01-13 | Amgen Inc | Variants of activin iib receptor polypeptides and uses thereof |
| US8138142B2 (en) | 2009-01-13 | 2012-03-20 | Acceleron Pharma Inc. | Methods for increasing adiponectin in a patient in need thereof |
| US20110294734A1 (en) | 2009-02-05 | 2011-12-01 | Digna Biotech, S.L. | Pharmaceutical compositions comprising tgf-beta 1 inhibitor peptides |
| EA201650137A1 (ru) | 2009-04-27 | 2017-09-29 | Новартис Аг | Композиции и способы для усиления мышечного роста |
| MX2011013172A (es) | 2009-06-08 | 2012-04-02 | Acceleron Pharma Inc | Metodos para aumentar adipocitos termogenicos. |
| 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 |
| NZ623113A (en) * | 2009-08-13 | 2015-10-30 | Acceleron Pharma Inc | Combined use of gdf traps and erythropoietin receptor activators to increase red blood cell levels |
| MX385217B (es) | 2009-09-09 | 2025-03-14 | Acceleron Pharma Inc | Antagonistas de actriib y dosificación y usos de los mismos. |
| EP3818988A1 (en) | 2009-11-03 | 2021-05-12 | Acceleron Pharma Inc. | Methods for treating fatty liver disease |
| CA2781152A1 (en) | 2009-11-17 | 2011-05-26 | Acceleron Pharma Inc. | Actriib proteins and variants and uses therefore relating to utrophin induction for muscular dystrophy therapy |
| RU2421126C1 (ru) | 2010-01-25 | 2011-06-20 | ФГУ ВПО Кубанский государственный медицинский университет Росздрава (КГМУ) | Способ прогнозирования эффективности планируемой стандартной терапии острого нефрита |
| WO2012027065A2 (en) | 2010-08-27 | 2012-03-01 | Celgene Corporation | Combination therapy for treatment of disease |
| CA2852683A1 (en) | 2011-10-17 | 2013-04-25 | Acceleron Pharma, Inc. | Methods and compositions for treating ineffective erythropoiesis |
| WO2014007198A1 (ja) | 2012-07-02 | 2014-01-09 | 協和発酵キリン株式会社 | 抗ｂｍｐ９抗体を有効成分とする、腎性貧血、がん性貧血などの貧血に対する治療剤 |
| CN113604550A (zh) | 2012-10-24 | 2021-11-05 | 细胞基因公司 | 用于治疗贫血症的生物标志物 |
| CA2889286A1 (en) | 2012-10-24 | 2014-05-01 | Celgene Corporation | Methods for treating anemia |
| ES2884095T3 (es) | 2012-11-02 | 2021-12-10 | Celgene Corp | Antagonistas de activina-actrii y usos para el tratamiento de trastornos óseos y otros trastornos |
| EP3808778A1 (en) | 2014-04-18 | 2021-04-21 | Acceleron Pharma Inc. | Methods for increasing red blood cell levels and treating sickle-cell disease |
| MA40008A (fr) | 2014-06-13 | 2021-05-05 | Acceleron Pharma Inc | Antagoniste actrii pour le traitement et la prevention d'un ulcere cutane chez un sujet ayant l'anemie |
| MA41052A (fr) | 2014-10-09 | 2017-08-15 | Celgene Corp | Traitement d'une maladie cardiovasculaire à l'aide de pièges de ligands d'actrii |
| MA41119A (fr) | 2014-12-03 | 2017-10-10 | Acceleron Pharma Inc | Méthodes de traitement de syndromes myélodysplasiques et d'anémie sidéroblastique |
| IL252631B2 (en) | 2014-12-03 | 2024-06-01 | Celgene Corp | ACTIVIN-ACTRII antagonists and uses for the treatment of anemia |
| KR101759725B1 (ko) * | 2015-04-27 | 2017-08-01 | 동우당제약(주) | 지골피추출물로부터 분리된 디하이드로파세익 애시드 쓰리프라임-오-베타-디-글루코피라노사이드를 포함하는 골다공증 예방 및 치료용 조성물 |
| EP3294320A4 (en) | 2015-05-13 | 2018-12-26 | Celgene Corporation | Treatment of beta-thalassemia using actrii ligand traps |
| CA2986432A1 (en) | 2015-05-20 | 2016-11-24 | Celgene Corporation | In vitro cell culture methods for beta-thalassemia using activin type ii receptor ligand traps |
| US11123430B2 (en) | 2015-11-04 | 2021-09-21 | Acceleron Pharma Inc. | Methods for increasing red blood cell levels and treating ineffective erythropoiesis |
| EP3380121B1 (en) | 2015-11-23 | 2023-12-20 | Acceleron Pharma Inc. | Actrii antagonist for use in treating eye disorders |
| KR102144203B1 (ko) | 2016-05-27 | 2020-08-12 | 노벨리스 인크. | Ｈｖａｃ＆ｒ 시스템들에 사용을 위한 고 강도 및 내부식성 합금 |
| RS62011B1 (sr) | 2016-07-15 | 2021-07-30 | Acceleron Pharma Inc | Kompozicije koje sadrže polipeptide actriia za upotrebu u lečenju plućne hipertenzije |
| RS65735B1 (sr) | 2016-07-27 | 2024-08-30 | Acceleron Pharma Inc | Kompozicije za upotrebu u lečenju mijelofibroze |
| AU2017338916B2 (en) | 2016-10-05 | 2022-03-24 | Acceleron Pharma Inc. | Variant ActRIIB proteins and uses thereof |
| DK3638243T3 (da) | 2017-06-14 | 2024-10-28 | Celgene Corp | Fremgangsmåder til behandling af myeloproliferativ neoplasma-forbundet myelofibrose og anæmi |
| JP7663502B2 (ja) | 2018-10-31 | 2025-04-16 | セルジーン コーポレイション | 環状鉄芽球が見られる対象における非常に低リスク、低リスクまたは中程度のリスクの骨髄異形成症候群による貧血の、アクチビン－ａｃｔｒｉｉリガンドトラップを用いた治療 |
| CN115427056A (zh) | 2020-04-13 | 2022-12-02 | 细胞基因公司 | 使用actriib配体陷阱和菲卓替尼治疗贫血的方法 |
| CA3177632A1 (en) | 2020-05-15 | 2021-11-18 | Melih ACAR | Methods and compositions for treating anemia using actriib ligand traps and mtor inhibitors |
-
2015
- 2015-10-07 MA MA041052A patent/MA41052A/fr unknown
- 2015-10-08 HK HK18104109.0A patent/HK1244741A1/zh unknown
- 2015-10-08 MX MX2017004675A patent/MX392749B/es unknown
- 2015-10-08 EP EP15855379.2A patent/EP3204118B8/en active Active
- 2015-10-08 JP JP2017518975A patent/JP2017533191A/ja active Pending
- 2015-10-08 CA CA2964129A patent/CA2964129A1/en active Pending
- 2015-10-08 RU RU2017115720A patent/RU2017115720A/ru unknown
- 2015-10-08 AU AU2015339786A patent/AU2015339786B2/en not_active Ceased
- 2015-10-08 ES ES15855379T patent/ES2978963T3/es active Active
- 2015-10-08 TW TW104133276A patent/TW201625288A/zh unknown
- 2015-10-08 US US15/517,782 patent/US11813308B2/en active Active
- 2015-10-08 KR KR1020177012406A patent/KR20170088836A/ko not_active Ceased
- 2015-10-08 CN CN201580067355.5A patent/CN107206255A/zh active Pending
- 2015-10-08 WO PCT/US2015/054674 patent/WO2016069234A1/en not_active Ceased
- 2015-10-08 TW TW111117000A patent/TW202300170A/zh unknown
-
2017
- 2017-04-07 IL IL251649A patent/IL251649B/en unknown
-
2021
- 2021-06-01 AU AU2021203571A patent/AU2021203571A1/en not_active Abandoned
- 2021-07-02 JP JP2021110451A patent/JP2021169464A/ja active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| RU2017115720A (ru) | 2018-11-15 |
| AU2021203571A1 (en) | 2021-07-01 |
| IL251649A0 (en) | 2017-06-29 |
| ES2978963T3 (es) | 2024-09-23 |
| IL251649B (en) | 2022-02-01 |
| US11813308B2 (en) | 2023-11-14 |
| TW202300170A (zh) | 2023-01-01 |
| EP3204118B1 (en) | 2024-03-06 |
| KR20170088836A (ko) | 2017-08-02 |
| RU2017115720A3 (enExample) | 2019-05-08 |
| CA2964129A1 (en) | 2016-05-06 |
| EP3204118A4 (en) | 2018-10-03 |
| EP3204118A1 (en) | 2017-08-16 |
| EP3204118B8 (en) | 2024-04-10 |
| CN107206255A (zh) | 2017-09-26 |
| MX2017004675A (es) | 2018-06-12 |
| JP2017533191A (ja) | 2017-11-09 |
| HK1244741A1 (zh) | 2018-08-17 |
| AU2015339786B2 (en) | 2021-03-04 |
| MX392749B (es) | 2025-03-24 |
| WO2016069234A1 (en) | 2016-05-06 |
| JP2021169464A (ja) | 2021-10-28 |
| MA41052A (fr) | 2017-08-15 |
| AU2015339786A1 (en) | 2017-05-25 |
| US20170304397A1 (en) | 2017-10-26 |
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