JP6669673B2 - 潰瘍を処置するための方法および組成物 - Google Patents
潰瘍を処置するための方法および組成物 Download PDFInfo
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| 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 |
| US10098857B2 (en) | 2008-10-10 | 2018-10-16 | The Board Of Trustees Of The Leland Stanford Junior University | Topical and transdermal delivery of HIF-1 modulators to prevent and treat chronic wounds |
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| US11123430B2 (en) | 2015-11-04 | 2021-09-21 | Acceleron Pharma Inc. | Methods for increasing red blood cell levels and treating ineffective erythropoiesis |
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| WO2018022762A1 (en) * | 2016-07-27 | 2018-02-01 | Acceleron Pharma Inc. | Methods and compositions for treating myelofibrosis |
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| CN119591692A (zh) | 2016-11-10 | 2025-03-11 | 科乐斯疗法公司 | 激活素受体iia型变体及其使用方法 |
| FI3638243T3 (fi) | 2017-06-14 | 2024-10-29 | Celgene Corp | Menetelmiä myeloproliferatiivin neoplasma-assosioidun myelofibroosin ja anemian hoitamiseksi |
| US11331288B2 (en) | 2017-09-14 | 2022-05-17 | The Board Of Trustees Of The Leland Stanford Junior University | Conditioning irradiated tissue for increasing vascularity |
| US11484573B2 (en) | 2017-11-09 | 2022-11-01 | Keros Therapeutics, Inc. | Activin receptor type IIa variants and methods of use thereof |
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| AU2019244105A1 (en) * | 2018-03-27 | 2020-10-15 | Tautona Group Ip Holding Company, L.L.C. | Topical and transdermal delivery of an iron chelator to prevent and treat chronic wounds |
| CA3098679A1 (en) | 2018-05-09 | 2019-11-14 | Keros Therapeutics, Inc. | Activin receptor type iia variants and methods of use thereof |
| WO2021189010A1 (en) | 2020-03-20 | 2021-09-23 | Keros Therapeutics, Inc. | Methods of using activin receptor type iib variants |
| CN115768457A (zh) | 2020-03-20 | 2023-03-07 | 科乐斯疗法公司 | 激活素受体ii型嵌合体以及其使用方法 |
| US12186370B1 (en) | 2020-11-05 | 2025-01-07 | Celgene Corporation | ACTRIIB ligand trap compositions and uses thereof |
Family Cites Families (255)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| JPH0637520B2 (ja) | 1985-07-03 | 1994-05-18 | 味の素株式会社 | ポリペプチド |
| US6548640B1 (en) | 1986-03-27 | 2003-04-15 | Btg International Limited | Altered antibodies |
| US4973577A (en) | 1986-04-04 | 1990-11-27 | The Salk Institute For Biological Studies | FSH-releasing peptides |
| 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 |
| US5080891A (en) | 1987-08-03 | 1992-01-14 | Ddi Pharmaceuticals, Inc. | Conjugates of superoxide dismutase coupled to high molecular weight polyalkylene glycols |
| US5223409A (en) | 1988-09-02 | 1993-06-29 | Protein Engineering Corp. | Directed evolution of novel binding proteins |
| DE68913658T3 (de) | 1988-11-11 | 2005-07-21 | Stratagene, La Jolla | Klonierung von Immunglobulin Sequenzen aus den variablen Domänen |
| US5096815A (en) | 1989-01-06 | 1992-03-17 | Protein Engineering Corporation | Generation and selection of novel dna-binding proteins and polypeptides |
| US5198346A (en) | 1989-01-06 | 1993-03-30 | Protein Engineering Corp. | Generation and selection of novel DNA-binding proteins and polypeptides |
| WO1990008822A1 (en) | 1989-02-03 | 1990-08-09 | Genetics Institute, Inc. | Erythropoietin receptor |
| DE3920358A1 (de) | 1989-06-22 | 1991-01-17 | Behringwerke Ag | Bispezifische und oligospezifische, mono- und oligovalente antikoerperkonstrukte, ihre herstellung und verwendung |
| US6150584A (en) | 1990-01-12 | 2000-11-21 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US6075181A (en) | 1990-01-12 | 2000-06-13 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
| US5475096A (en) | 1990-06-11 | 1995-12-12 | University Research Corporation | Nucleic acid ligands |
| US5580737A (en) | 1990-06-11 | 1996-12-03 | Nexstar Pharmaceuticals, Inc. | High-affinity nucleic acid ligands that discriminate between theophylline and caffeine |
| US5763177A (en) | 1990-06-11 | 1998-06-09 | Nexstar Pharmaceuticals, Inc. | Systematic evolution of ligands by exponential enrichment: photoselection of nucleic acid ligands and solution selex |
| US5567588A (en) | 1990-06-11 | 1996-10-22 | University Research Corporation | Systematic evolution of ligands by exponential enrichment: Solution SELEX |
| US5707796A (en) | 1990-06-11 | 1998-01-13 | Nexstar Pharmaceuticals, Inc. | Method for selecting nucleic acids on the basis of structure |
| US5270163A (en) | 1990-06-11 | 1993-12-14 | University Research Corporation | Methods for identifying nucleic acid ligands |
| US5770429A (en) | 1990-08-29 | 1998-06-23 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
| WO1992004913A1 (en) | 1990-09-13 | 1992-04-02 | Children's Hospital Medical Center Of Northern California | Method for increasing red blood cell production by treatment with activin or activin-related peptides |
| ATE164395T1 (de) | 1990-12-03 | 1998-04-15 | Genentech Inc | Verfahren zur anreicherung von proteinvarianten mit geänderten bindungseigenschaften |
| US5571894A (en) | 1991-02-05 | 1996-11-05 | Ciba-Geigy Corporation | Recombinant antibodies specific for a growth factor receptor |
| US5118667A (en) | 1991-05-03 | 1992-06-02 | Celtrix Pharmaceuticals, Inc. | Bone growth factors and inhibitors of bone resorption for promoting bone formation |
| US6162896A (en) | 1991-05-10 | 2000-12-19 | The Salk Institute For Biological Studies | Recombinant vertebrate activin receptors |
| CA2086327A1 (en) | 1991-05-10 | 1992-11-11 | Lawrence S. Mathews | Cloning and recombinant production of receptor(s) of the activin/tgf- .beta. superfamily |
| US5885794A (en) | 1991-05-10 | 1999-03-23 | The Salk Institute For Biological Studies | Recombinant production of vertebrate activin receptor polypeptides and identification of receptor DNAs in the activin/TGF-β superfamily |
| US20050186593A1 (en) | 1991-05-10 | 2005-08-25 | The Salk Institute For Biological Studies | Cloning and recombinant production of CRF receptor(s) |
| WO1992022653A1 (en) | 1991-06-14 | 1992-12-23 | Genentech, Inc. | Method for making humanized antibodies |
| US6287816B1 (en) | 1991-06-25 | 2001-09-11 | Genetics Institute, Inc. | BMP-9 compositions |
| KR100255415B1 (ko) | 1991-06-25 | 2000-05-01 | 브루스 엠. 에이센 | 비엠피-9 조성물 |
| GB9114948D0 (en) | 1991-07-11 | 1991-08-28 | Pfizer Ltd | Process for preparing sertraline intermediates |
| FI941572A7 (fi) | 1991-10-07 | 1994-05-27 | Oncologix Inc | Anti-erbB-2-monoklonaalisten vasta-aineiden yhdistelmä ja käyttömenete lmä |
| ATE503496T1 (de) | 1992-02-06 | 2011-04-15 | Novartis Vaccines & Diagnostic | Biosynthetisches bindeprotein für tumormarker |
| US6692925B1 (en) | 1992-11-17 | 2004-02-17 | Ludwig Institute For Cancer Research | Proteins having serine/threonine kinase domains, corresponding nucleic acid molecules, and their use |
| EP0679163A4 (en) | 1993-01-12 | 1997-07-16 | Univ Johns Hopkins Med | GROWTH DIFFERENTIATION FACTOR-3. |
| DE69433742T2 (de) | 1993-05-12 | 2005-07-07 | Genetics Institute, LLC, Cambridge | Bmp-10 zusammensetzungen |
| 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 |
| 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 |
| 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 |
| US5885574A (en) | 1994-07-26 | 1999-03-23 | Amgen Inc. | Antibodies which activate an erythropoietin receptor |
| 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 |
| JPH11502717A (ja) | 1995-04-11 | 1999-03-09 | ザ ジェネラル ホスピタル コーポレーション | 逆ツーハイブリッドシステム |
| US5869046A (en) | 1995-04-14 | 1999-02-09 | Genentech, Inc. | Altered polypeptides with increased half-life |
| US6699843B2 (en) | 1995-06-07 | 2004-03-02 | Gilead Sciences, Inc. | Method for treatment of tumors using nucleic acid ligands to PDGF |
| US6132988A (en) | 1995-10-27 | 2000-10-17 | Takeda Chemical Industries, Ltd. | DNA encoding a neuronal cell-specific receptor protein |
| GB9526131D0 (en) | 1995-12-21 | 1996-02-21 | Celltech Therapeutics Ltd | Recombinant chimeric receptors |
| US6004780A (en) | 1996-03-26 | 1999-12-21 | Human Genome Sciences, Inc. | Growth factor HTTER36 |
| US20050244867A1 (en) | 1996-03-26 | 2005-11-03 | Human Genome Sciences, Inc. | Growth factor HTTER36 |
| BR9712675A (pt) | 1996-10-25 | 1999-10-19 | Searle & Co | Agonistas do receptor de eritropoietina circularmente permutados. |
| US6605699B1 (en) | 1997-01-21 | 2003-08-12 | Human Genome Sciences, Inc. | Galectin-11 polypeptides |
| US6034062A (en) | 1997-03-13 | 2000-03-07 | Genetics Institute, Inc. | Bone morphogenetic protein (BMP)-9 compositions and their uses |
| US6231880B1 (en) | 1997-05-30 | 2001-05-15 | Susan P. Perrine | Compositions and administration of compositions for the treatment of blood disorders |
| US6011577A (en) | 1997-06-30 | 2000-01-04 | Polaroid Corporation | Modular optical print head assembly |
| 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 |
| 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 |
| US6953662B2 (en) | 1997-08-29 | 2005-10-11 | Human Genome Sciences, Inc. | Follistatin-3 |
| AU8921698A (en) | 1997-08-29 | 1999-03-16 | Human Genome Sciences, Inc. | Follistatin-3 |
| BR9812846A (pt) | 1997-10-03 | 2000-08-08 | Chugai Pharmaceutical Co Ltd | Anticorpo humanizado natural |
| US6610833B1 (en) | 1997-11-24 | 2003-08-26 | The Institute For Human Genetics And Biochemistry | Monoclonal human natural antibodies |
| BR9813365A (pt) | 1997-12-05 | 2004-06-15 | Scripps Research Inst | Método para produção e humanização de um anticorpo monoclonal de rato |
| US6696411B1 (en) | 1998-04-22 | 2004-02-24 | Cornell Research Foundation, Inc. | Canine erythropoietin gene and recombinant protein |
| US6335155B1 (en) | 1998-06-26 | 2002-01-01 | Sunesis Pharmaceuticals, Inc. | Methods for rapidly identifying small organic molecule ligands for binding to biological target molecules |
| 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 |
| CA2343715C (en) | 1998-09-22 | 2004-05-18 | 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 |
| US6238860B1 (en) | 1998-11-05 | 2001-05-29 | Dyax Corp. | Binding moieties for human parvovirus B19 |
| 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 |
| CA2355215A1 (en) | 1998-12-28 | 2000-07-06 | Jim Wells | Identifying small organic molecule ligands for binding |
| US6737056B1 (en) | 1999-01-15 | 2004-05-18 | Genentech, Inc. | Polypeptide variants with altered effector function |
| JP2003517580A (ja) | 1999-01-21 | 2003-05-27 | メタモーフイクス・インコーポレーテツド | 増殖分化因子インヒビター及びそれらの用途 |
| US6914128B1 (en) | 1999-03-25 | 2005-07-05 | Abbott Gmbh & Co. Kg | Human antibodies that bind human IL-12 and methods for producing |
| AU777783B2 (en) | 1999-04-19 | 2004-10-28 | Kyowa Hakko Kogyo Co. Ltd. | Proliferation inhibitor for androgen-independent tumor |
| US6468543B1 (en) | 1999-05-03 | 2002-10-22 | Zymogenetics, Inc. | Methods for promoting growth of bone using ZVEGF4 |
| DE60042021D1 (de) | 1999-07-29 | 2009-05-28 | Gilead Sciences Inc | Nukleinsäureliganden für den hepatozytischen wachstumsfaktor/dispersionsfaktor (hgf/sf) und seines c-met rezeptors |
| HRP20020387A2 (en) | 1999-11-12 | 2005-10-31 | Maxygen Holdings Ltd. | Interferon gamma conjugates |
| EP1240319A1 (en) | 1999-12-15 | 2002-09-18 | Genentech, Inc. | Shotgun scanning, a combinatorial method for mapping functional protein epitopes |
| DE60026592T2 (de) | 1999-12-15 | 2006-12-14 | Research Development Foundation, Carson City | Betaglycan als ein inhibin rezeptor und dessen verwendung |
| US20030224501A1 (en) | 2000-03-17 | 2003-12-04 | Young Paul E. | Bone morphogenic protein polynucleotides, polypeptides, and antibodies |
| JP4487376B2 (ja) | 2000-03-31 | 2010-06-23 | 味の素株式会社 | 腎疾患治療剤 |
| HUP0300369A2 (hu) | 2000-04-11 | 2003-06-28 | Genentech, Inc. | Többértékű antitestek és alkalmazásuk |
| CZ304855B6 (cs) | 2000-05-15 | 2014-12-10 | F. Hoffmann-La Roche Ag | Kapalná farmaceutická kompozice obsahující pegylovaný lidský erythropoetin, způsob její přípravy, léčivo pro léčení chorob korelujících s anemií při chronickém renálním selhání a zařízení s jejím obsahem |
| US6627424B1 (en) | 2000-05-26 | 2003-09-30 | Mj Bioworks, Inc. | Nucleic acid modifying enzymes |
| US20030215913A1 (en) | 2000-07-19 | 2003-11-20 | Enrique Alvarez | 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) |
| US7087224B2 (en) | 2000-10-31 | 2006-08-08 | Amgen Inc. | Method of treating anemia by administering IL-1ra |
| US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
| AU2567002A (en) | 2000-11-20 | 2002-05-27 | Univ Illinois | Membrane scaffold proteins |
| DE60131456T2 (de) | 2000-11-30 | 2008-07-10 | Medarex, Inc., Milpitas | Transchromosomale transgen-nagetiere zur herstellung von humanen antikörpern |
| AU2002236558A1 (en) | 2000-12-01 | 2002-06-11 | Regents Of The University Of California | Method and composition for modulating bone growth |
| US20030082233A1 (en) | 2000-12-01 | 2003-05-01 | Lyons Karen M. | Method and composition for modulating bone growth |
| TWI329129B (en) | 2001-02-08 | 2010-08-21 | 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 |
| WO2002074340A1 (fr) | 2001-03-16 | 2002-09-26 | Takeda Chemical Industries, Ltd. | Procede de fabrication d'une preparation a liberation continue |
| JP2004535182A (ja) | 2001-05-24 | 2004-11-25 | ザイモジェネティクス,インコーポレイティド | Taci−免疫グロブリン融合タンパク質 |
| CA2448253A1 (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 |
| 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 |
| CA2452246A1 (en) | 2001-07-17 | 2003-01-30 | Teijin Limited | Method of screening substance by measuring ppar .delta. activating effect and agent |
| 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 |
| CA2467689C (en) | 2001-12-06 | 2013-10-01 | Fibrogen, Inc. | Stabilization of hypoxia inducible factor (hif) alpha using inhibitors of hif prolyl hydroxylase |
| US20060234918A1 (en) | 2001-12-19 | 2006-10-19 | Voyager Pharmaceutical Corporation | Methods for treating and preventing cancers that express the hypothalamic-pituitary-gonadal axis of hormones and receptors |
| 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 |
| US20030224397A1 (en) | 2002-02-11 | 2003-12-04 | Genentech, Inc. | Antibody variants with faster antigen association rates |
| BR0307907A2 (pt) | 2002-02-21 | 2011-07-05 | Wyeth Corp | gasp1: proteìna contendo domìnio de folistatina |
| US20030219846A1 (en) | 2002-02-28 | 2003-11-27 | Pfizer Inc. | Assay for activity of the ActRIIB kinase |
| US8053552B2 (en) | 2002-04-18 | 2011-11-08 | Mtm Laboratories, Ag | Neopeptides and methods useful for detection and treatment of cancer |
| JP4753578B2 (ja) | 2002-06-03 | 2011-08-24 | ジェネンテック, インコーポレイテッド | 合成抗体ファージライブラリー |
| DE10234192B4 (de) | 2002-07-26 | 2009-11-26 | Epoplus Gmbh Co.Kg | Verwendung von Erythropoetin |
| 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 |
| WO2004065416A2 (en) | 2003-01-16 | 2004-08-05 | Genentech, Inc. | Synthetic antibody phage libraries |
| NZ541593A (en) | 2003-02-07 | 2009-05-31 | Prometic Biosciences Inc | Medium-chain length fatty acids, glycerides and analogues as stimulators of erythropoiesis |
| US20040197828A1 (en) | 2003-03-26 | 2004-10-07 | Gaddy Dana P. | Method for diagnosis and treatment of bone turnover |
| WO2005028517A2 (en) | 2003-05-09 | 2005-03-31 | The General Hospital Corporation | SOLUBLE TGF-β TYPE III RECEPTOR FUSION PROTEINS |
| BRPI0410927A (pt) | 2003-06-02 | 2006-06-27 | Wyeth Corp | métodos terapêuticos e profiláticos para distúrbios neuromusculares |
| NO345763B1 (no) | 2003-06-16 | 2021-07-19 | Celltech R&D Inc | Immunogen og antistoffer spesifikke for sklerostin, samt farmasøytiske preparater for å øke benmineralisering. |
| 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 |
| 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 |
| AU2005206277B2 (en) | 2004-01-22 | 2011-06-23 | 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 |
| AU2005229072A1 (en) | 2004-03-26 | 2005-10-13 | Acceleron Pharma Inc. | BMP-3 propeptides and related methods |
| ZA200608130B (en) | 2004-03-31 | 2008-12-31 | Genentech Inc | Humanized anti-TGF-beta antibodies |
| 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 |
| US7785903B2 (en) | 2004-04-09 | 2010-08-31 | Genentech, Inc. | Variable domain library and uses |
| EP2374817B1 (en) | 2004-04-13 | 2017-09-06 | F. Hoffmann-La Roche AG | Anti-P-selectin antibodies |
| WO2005113590A2 (en) | 2004-05-12 | 2005-12-01 | Acceleron Pharma Inc. | Bmp10 propeptides and related methods |
| CA2572330A1 (en) | 2004-06-24 | 2006-01-05 | Acceleron Pharma Inc. | Gdf3 propeptides and related methods |
| EP1771470B1 (en) | 2004-07-23 | 2013-06-26 | Acceleron Pharma Inc. | Actrii receptor polypeptides, methods and compositions |
| WO2006012527A1 (en) | 2004-07-23 | 2006-02-02 | Endocyte, Inc. | Bivalent linkers and conjugates thereof |
| US8617815B2 (en) | 2004-08-05 | 2013-12-31 | The Regents Of The University Of California | Molecules with effects on cellular development and function |
| BRPI0514253A (pt) | 2004-08-12 | 2008-06-03 | Wyeth Corp | terapia de combinação para diabetes, obesidade e doenças cardiovasculares usando composições contendo inibidores de gdf-8 |
| TWI380996B (zh) | 2004-09-17 | 2013-01-01 | Hoffmann La Roche | 抗ox40l抗體 |
| SI1791565T1 (sl) | 2004-09-23 | 2016-08-31 | Genentech, Inc. | Cisteinsko konstruirana protitelesa in konjugati |
| WO2006039400A2 (en) | 2004-09-29 | 2006-04-13 | Mount Sinai School Of Medicine Of New York University | Fsh and fsh receptor modulator compositions and methods for inhibiting osteoclastic bone resorption and bone loss in osteoporosis |
| NZ538097A (en) | 2005-02-07 | 2006-07-28 | Ovita Ltd | Method and compositions for improving wound healing |
| EP2954903A1 (en) | 2005-02-16 | 2015-12-16 | The General Hospital Corporation | Use of bmp antagonists to regulate hepcidin-mediated iron metabolism |
| WO2006115274A1 (ja) | 2005-04-26 | 2006-11-02 | Ajinomoto Co., Inc. | 骨髄赤血球前駆細胞分化促進剤 |
| NZ612578A (en) | 2005-08-19 | 2014-11-28 | Abbvie Inc | Dual variable domain immunoglobin and uses thereof |
| JP2007099764A (ja) | 2005-09-09 | 2007-04-19 | Ajinomoto Co Inc | 血糖低下剤 |
| PT1931697E (pt) | 2005-09-28 | 2010-12-06 | Zymogenetics Inc | Antagonistas de il-17a e il-17f e processos para a sua utilização |
| US8067562B2 (en) | 2005-11-01 | 2011-11-29 | Amgen Inc. | Isolated nucleic acid molecule comprising the amino acid sequence of SEQ ID NO:1 |
| US8679490B2 (en) | 2005-11-07 | 2014-03-25 | Genentech, Inc. | Binding polypeptides with diversified and consensus VH/VL hypervariable sequences |
| AU2006318449B2 (en) | 2005-11-23 | 2012-07-05 | Acceleron Pharma Inc. | Activin-actRIIa antagonists and uses for promoting bone growth |
| US8128933B2 (en) | 2005-11-23 | 2012-03-06 | Acceleron Pharma, Inc. | Method of promoting bone growth by an anti-activin B antibody |
| US20070237764A1 (en) | 2005-12-02 | 2007-10-11 | Genentech, Inc. | Binding polypeptides with restricted diversity sequences |
| WO2007067616A2 (en) | 2005-12-06 | 2007-06-14 | Amgen Inc | Uses of myostatin antagonists |
| WO2007071023A1 (en) | 2005-12-20 | 2007-06-28 | Merck Frosst Canada Ltd. | Heteroaromatic compounds as inhibitors of stearoyl-coenzyme a delta-9 desaturase |
| BRPI0620255A2 (pt) | 2005-12-21 | 2011-11-08 | Schering Corp | uso de agentes redutores de colesterol e/ou antagonista/agonista inverso do receptor de h3 |
| WO2007076127A2 (en) | 2005-12-22 | 2007-07-05 | Biogen Idec Ma Inc | Condensed imidazoles or pyrazoles and their use as transforming growth factor modulators |
| EP1976541B1 (en) | 2006-01-20 | 2011-07-13 | Beckman Coulter, Inc. | Low hemoglobin concentration cell percentage and method of use in detection of iron deficiency |
| EP1976377A4 (en) | 2006-01-25 | 2010-06-23 | Wellstat Therapeutics Corp | COMPOUNDS FOR THE TREATMENT OF METABOLIC DISORDERS |
| KR20080098615A (ko) | 2006-02-28 | 2008-11-11 | 웰스태트 테러퓨틱스 코포레이션 | 물질대사 장애의 치료용 화합물 |
| EP2007813A2 (en) | 2006-04-14 | 2008-12-31 | Amgen Inc. | Agonist erythropoietin receptor antibodies |
| WO2007123391A1 (en) | 2006-04-20 | 2007-11-01 | Academisch Ziekenhuis Leiden | Therapeutic intervention in a genetic disease in an individual by modifying expression of an aberrantly expressed gene. |
| WO2007133653A2 (en) | 2006-05-09 | 2007-11-22 | Hemaquest Pharmaceuticals, Inc. | Methods for treating blood disorders |
| CA2651567A1 (en) | 2006-05-09 | 2007-11-22 | Genentech, Inc. | Binding polypeptides with optimized scaffolds |
| WO2008011126A2 (en) | 2006-07-21 | 2008-01-24 | Lyne Laboratories | Liquid compositions of calcium acetate |
| 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 |
| US20100003190A1 (en) | 2006-12-08 | 2010-01-07 | Caritas St. Elizabeth's Medical Center Of Boston, Inc. | Method for protecting renal tubular epithelial cells from radiocontrast nephropathy (RCN) |
| CA2672581A1 (en) | 2006-12-14 | 2008-06-19 | Forerunner Pharma Research Co., Ltd. | Anti-claudin 3 monoclonal antibody and treatment and diagnosis of cancer using the same |
| US8895016B2 (en) | 2006-12-18 | 2014-11-25 | Acceleron Pharma, Inc. | Antagonists of activin-actriia and uses for increasing red blood cell levels |
| EA035911B1 (ru) | 2006-12-18 | 2020-08-31 | Акселерон Фарма Инк. | Применение полипептида, который ингибирует опосредованный активином сигнальный путь, в качестве лекарственного средства |
| US20100028332A1 (en) | 2006-12-18 | 2010-02-04 | Acceleron Pharma Inc. | Antagonists of actriib and uses for increasing red blood cell levels |
| TR200906131T1 (tr) | 2007-02-01 | 2009-11-23 | Acceleron Pharma Inc. | Aktivin -actrIIa antagonistleri ve göğüs kanserinin tedavi e |
| TWI782836B (zh) * | 2007-02-02 | 2022-11-01 | 美商艾瑟勒朗法瑪公司 | 衍生自ActRIIB的變體與其用途 |
| CN104548056B (zh) | 2007-02-09 | 2022-09-09 | 阿塞勒隆制药公司 | 活化素-actriia拮抗剂和促进癌症患者骨骼生长的用途 |
| TWI573802B (zh) | 2007-03-06 | 2017-03-11 | 安美基公司 | 變異之活動素受體多肽及其用途 |
| US8501678B2 (en) | 2007-03-06 | 2013-08-06 | Atara Biotherapeutics, Inc. | Variant activin receptor polypeptides and uses thereof |
| CN100592373C (zh) | 2007-05-25 | 2010-02-24 | 群康科技(深圳)有限公司 | 液晶显示面板驱动装置及其驱动方法 |
| US20090017019A1 (en) | 2007-06-01 | 2009-01-15 | 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 |
| GB0715087D0 (en) | 2007-08-03 | 2007-09-12 | Summit Corp Plc | Drug combinations for the treatment of duchenne muscular dystrophy |
| PE20090510A1 (es) | 2007-08-03 | 2009-05-22 | Summit Corp Plc | Combinaciones de drogas para el tratamiento de la distrofia muscular de duchenne |
| 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 |
| WO2009035629A1 (en) | 2007-09-13 | 2009-03-19 | Ludwig Institute Of Cancer Research | Method for modifying cellular immune response by modulating activin activity |
| US7960343B2 (en) | 2007-09-18 | 2011-06-14 | Acceleron Pharma Inc. | Activin-ActRIIa antagonists and uses for decreasing or inhibiting FSH secretion |
| PE20091163A1 (es) | 2007-11-01 | 2009-08-09 | Wyeth Corp | Anticuerpos para gdf8 |
| EA201000844A1 (ru) | 2007-11-21 | 2011-10-31 | Амген Инк. | Связывающие wise агенты и эпитопы |
| WO2009114180A1 (en) | 2008-03-13 | 2009-09-17 | The General Hospital Corporation | Inhibitors of the bmp signaling pathway |
| JP2011523357A (ja) | 2008-05-06 | 2011-08-11 | ジョスリン ダイアビーティス センター インコーポレイテッド | 褐色脂肪細胞分化を誘導するための方法および組成物 |
| WO2009137075A1 (en) | 2008-05-06 | 2009-11-12 | Acceleron Pharma Inc. | Anti-activin antibodies and uses for promoting bone growth |
| NZ602471A (en) * | 2008-06-26 | 2014-10-31 | Acceleron Pharma Inc | Antagonists of activin-actriia and uses for increasing red blood cell levels |
| KR101871510B1 (ko) | 2008-06-26 | 2018-06-26 | 악셀레론 파마 인코포레이티드 | 액티빈-actriia 길항물질을 투약하는 방법 및 치료된 환자의 모니터링 |
| DK2340031T3 (da) | 2008-08-14 | 2019-07-15 | Acceleron Pharma Inc | Gdf-fanger til anvendelse ved behandling af anæmi |
| 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 |
| US20110293526A1 (en) | 2008-11-20 | 2011-12-01 | University Of Southern California | Compositions and methods to modulate hair growth |
| UA107921C2 (en) | 2008-11-26 | 2015-03-10 | Amgen Inc | Variants of polypeptide of receptor ivr activin and their use |
| EP2387412A4 (en) | 2009-01-13 | 2013-04-03 | Acceleron Pharma Inc | PROCESS FOR INCREASING THE ADIPONECTIN MIRROR |
| US8110355B2 (en) | 2009-02-20 | 2012-02-07 | GenRemedy, LLC | Methods for identifying agents that inhibit cell migration, promote cell adhesion and prevent metastasis |
| SG174273A1 (en) | 2009-04-27 | 2011-10-28 | Novartis Ag | Compositions and methods for increasing muscle growth |
| EP2440576A4 (en) | 2009-06-08 | 2013-11-20 | Acceleron Pharma Inc | PROCESS FOR INCREASING THE NUMBER OF THERMOUS ADIPOCYTES |
| CN107267520A (zh) | 2009-06-12 | 2017-10-20 | 阿塞勒隆制药公司 | 截短的actriib‑fc融合蛋白 |
| EP3838919A1 (en) * | 2009-08-13 | 2021-06-23 | Acceleron Pharma Inc. | Combined use of gdf traps and erythropoietin receptor activators to increase red blood cell levels |
| KR20210029836A (ko) | 2009-09-09 | 2021-03-16 | 악셀레론 파마 인코포레이티드 | ActRIIb 길항제들와 이의 투약 및 용도 |
| EP3260130B1 (en) | 2009-11-03 | 2021-03-10 | Acceleron Pharma Inc. | Methods for treating fatty liver disease |
| AU2010322011B2 (en) | 2009-11-17 | 2016-03-31 | Acceleron Pharma Inc. | ActRIIB proteins and variants and uses therefore relating to utrophin induction for muscular dystrophy therapy |
| WO2012027065A2 (en) * | 2010-08-27 | 2012-03-01 | Celgene Corporation | Combination therapy for treatment of disease |
| US9595813B2 (en) | 2011-01-24 | 2017-03-14 | Soraa Laser Diode, Inc. | Laser package having multiple emitters configured on a substrate member |
| US8580922B2 (en) | 2011-03-04 | 2013-11-12 | Shire Human Genetic Therapies, Inc. | Peptide linkers for polypeptide compositions and methods for using same |
| ES2692519T3 (es) | 2011-07-01 | 2018-12-04 | Novartis Ag | Método para tratar trastornos metabólicos |
| ES2741477T3 (es) * | 2011-10-17 | 2020-02-11 | Acceleron Pharma Inc | Composiciones para tratar la sobrecarga de hierro en talasemia |
| WO2013063536A1 (en) * | 2011-10-27 | 2013-05-02 | Acceleron Pharma, Inc. | Actriib binding agents and uses thereof |
| US8765385B2 (en) | 2011-10-27 | 2014-07-01 | Ravindra Kumar | Method of detection of neutralizing anti-actriib antibodies |
| WO2013059876A1 (en) | 2011-10-28 | 2013-05-02 | Paranta Biosciences Limited | A method of treating mucus hypersecretion |
| BR112014015003A2 (pt) | 2011-12-19 | 2019-09-24 | Amgen Inc | composição farmacêutica, método para tratar um cancer e método para reduzir o tamanho de uma massa tumoral |
| US10501512B2 (en) | 2012-04-02 | 2019-12-10 | Modernatx, Inc. | Modified polynucleotides |
| US9102212B2 (en) | 2012-05-14 | 2015-08-11 | Paccar Inc | Fresh air system for heavy duty vehicle cab/sleeper combination |
| US9663569B2 (en) | 2012-06-14 | 2017-05-30 | The Medical Research, Infrastructure, And Health Services Fund Of The Tel Aviv Medical Center | Use of blocking agents of bone morphogenic protein (BMP) signalling for the treatment of neuroinflammatory and neurodegenerative diseases |
| CN104411720B (zh) | 2012-07-02 | 2018-05-11 | 协和发酵麒麟株式会社 | 以抗bmp9抗体作为有效成分的、对肾性贫血、癌性贫血等贫血的治疗剂 |
| JP6401171B2 (ja) | 2012-10-24 | 2018-10-03 | セルジーン コーポレイション | 貧血の治療に使用するためのバイオマーカー |
| NZ747350A (en) | 2012-10-24 | 2020-07-31 | Celgene Corp | Methods for treating anemia |
| WO2014064292A1 (en) | 2012-10-26 | 2014-05-01 | Universite Pierre Et Marie Curie (Paris 6) | A method for preventing or treating atrial fibrillation |
| MX366336B (es) | 2012-11-02 | 2019-07-05 | Celgene Corp | Antagonistas de activina - actrii y usos para el tratar trastornos oseos y otros. |
| KR102467714B1 (ko) | 2012-11-08 | 2022-11-16 | 클리어사이드 바이오메디컬, 인코포레이드 | 인간 대상체에서 안구 질병을 치료하기 위한 방법 및 장치 |
| WO2014093531A1 (en) | 2012-12-11 | 2014-06-19 | Los Angeles Biomedical Research Institute At Harbor-Ucla Medical Center | Modulation of myofiber repair by anti-myostatin in strategies with stem cells |
| US20140220033A1 (en) | 2013-02-01 | 2014-08-07 | Santa Maria Biotherapeutics, Inc. | Administration of an Anti-Activin-A Compound to a Subject |
| US20160184458A1 (en) | 2013-03-14 | 2016-06-30 | Shire Human Genetic Therapies, Inc. | Mrna therapeutic compositions and use to treat diseases and disorders |
| 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 |
| HK1219280A1 (zh) | 2013-08-14 | 2017-03-31 | Novartis Ag | 治疗偶发性包涵体肌炎之方法 |
| WO2015089575A1 (en) | 2013-12-16 | 2015-06-25 | Paranta Biosciences Limited | Method of diagnosis and treatment |
| WO2015108972A1 (en) | 2014-01-14 | 2015-07-23 | Santa Maria Biotherapeutics, Inc. | Activin inhibitor response prediction and uses for treatment |
| WO2015111008A2 (en) | 2014-01-27 | 2015-07-30 | Novartis Ag | Biomarkers predictive of muscle atrophy, method and use |
| JP6601687B2 (ja) | 2014-03-31 | 2019-11-06 | 大日本住友製薬株式会社 | 進行性骨化性線維異形成症の予防剤及び治療剤 |
| EP3808778A1 (en) | 2014-04-18 | 2021-04-21 | Acceleron Pharma Inc. | Methods for increasing red blood cell levels and treating sickle-cell disease |
| TW201622746A (zh) | 2014-04-24 | 2016-07-01 | 諾華公司 | 改善或加速髖部骨折術後身體復原之方法 |
| CA2950754C (en) | 2014-06-04 | 2021-10-26 | Acceleron Pharma, Inc. | Methods and compositions for treatment of disorders with follistatin polypeptides |
| BR112016029211A2 (pt) | 2014-06-13 | 2018-01-30 | Amgen Inc | composição, método para inibir um crescimento tumoral sólido em um indivíduo, método para produzir uma proteína, método para inibir, reduzir ou tratar de caquexia em um indivíduo, método para tratar obesidade ou uma doença associada à obesidade e kit |
| AU2015274277B2 (en) * | 2014-06-13 | 2021-03-18 | Acceleron Pharma, Inc. | Methods and compositions for treating ulcers |
| MA41119A (fr) * | 2014-12-03 | 2017-10-10 | Acceleron Pharma Inc | Méthodes de traitement de syndromes myélodysplasiques et d'anémie sidéroblastique |
| PT3286206T (pt) | 2015-04-22 | 2021-04-01 | Biogen Ma Inc | Novas proteínas híbridas bloqueadoras de ligando actriib para tratar doenças de desgaste muscular |
| TWI762444B (zh) * | 2015-05-13 | 2022-05-01 | 美商西建公司 | 使用ACTRII配位體捕捉以治療β-地中海型貧血 |
| WO2017091706A1 (en) * | 2015-11-23 | 2017-06-01 | Acceleron Pharma Inc. | Methods for treating eye disorders |
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| HK1243640A1 (zh) | 2018-07-20 |
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