AU2007248784B2 - RAGE fusion proteins, formulations, and methods of use thereof - Google Patents
RAGE fusion proteins, formulations, and methods of use thereof Download PDFInfo
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- AU2007248784B2 AU2007248784B2 AU2007248784A AU2007248784A AU2007248784B2 AU 2007248784 B2 AU2007248784 B2 AU 2007248784B2 AU 2007248784 A AU2007248784 A AU 2007248784A AU 2007248784 A AU2007248784 A AU 2007248784A AU 2007248784 B2 AU2007248784 B2 AU 2007248784B2
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Classifications
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- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
- C07K14/70503—Immunoglobulin superfamily
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- C07—ORGANIC CHEMISTRY
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- C12N15/09—Recombinant DNA-technology
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
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- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
- C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
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- Cardiology (AREA)
- Vascular Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
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Applications Claiming Priority (3)
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| US79845506P | 2006-05-05 | 2006-05-05 | |
| US60/798,455 | 2006-05-05 | ||
| PCT/US2007/010125 WO2007130302A2 (en) | 2006-05-05 | 2007-04-25 | Rage fusion proteins, formulations, and methods of use thereof |
Publications (2)
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| AU2007248784A1 AU2007248784A1 (en) | 2007-11-15 |
| AU2007248784B2 true AU2007248784B2 (en) | 2013-11-21 |
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| AU2007248784A Ceased AU2007248784B2 (en) | 2006-05-05 | 2007-04-25 | RAGE fusion proteins, formulations, and methods of use thereof |
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| EP (2) | EP2021474A2 (enExample) |
| JP (1) | JP5558810B2 (enExample) |
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| WO (1) | WO2007130302A2 (enExample) |
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| MX2007001559A (es) * | 2004-08-03 | 2007-04-10 | Transtech Pharma Inc | Proteinas de fusion de receptor para productos finales glicados avanzados y metodos de uso. |
| CA2575830A1 (en) * | 2004-08-03 | 2006-02-16 | Transtech Pharma, Inc. | Rage fusion proteins and methods of use |
| EP1963786B1 (en) * | 2005-12-23 | 2013-07-24 | GCoder Systems AB | Positioning pattern |
| CN101410411A (zh) * | 2006-02-09 | 2009-04-15 | 转化技术制药公司 | Rage融合蛋白及使用方法 |
| SG171670A1 (en) | 2006-05-05 | 2011-06-29 | Transtech Pharma Inc | Rage fusion proteins, formulations, and methods of use thereof |
| JP5241518B2 (ja) * | 2007-02-15 | 2013-07-17 | 国立大学法人九州大学 | 抗ｈｍｇｂ−１抗体を含む間質性肺疾患治療剤 |
| US8470325B2 (en) | 2007-02-15 | 2013-06-25 | Kagoshima University | Method of treating amykloidosis comprising administering an anti-HMGB-1 antibody |
| TW200846366A (en) * | 2007-02-15 | 2008-12-01 | Univ Fukuoka | Agent for suppressing rejection in organ transplantation comprising anti-hmgb-1 antibody |
| WO2008100470A2 (en) * | 2007-02-15 | 2008-08-21 | Transtech Pharma, Inc. | Rage - immunoglobulin fusion proteins |
| ES2564634T3 (es) | 2007-06-14 | 2016-03-28 | Galactica Pharmaceuticals, Inc. | Proteínas de fusión de RAGE |
| EP2421892A1 (en) | 2009-04-20 | 2012-02-29 | Pfizer Inc. | Control of protein glycosylation and compositions and methods relating thereto |
| WO2011102845A1 (en) * | 2010-02-18 | 2011-08-25 | Transtech Pharma, Inc. | Rage fusion protein compositions and methods of use |
| US9345770B2 (en) | 2011-11-16 | 2016-05-24 | University of Pittsburgh—of the Commonwealth System of Higher Education | Immunogenic tumor associated stromal cell antigen peptides and methods of their use |
| HUE043820T2 (hu) * | 2012-11-28 | 2019-09-30 | Nono Inc | Liofilizált TAT-NR2B9c készítmény |
| US10251935B2 (en) | 2012-11-28 | 2019-04-09 | Nono Inc. | Lyophilized formulation comprising tat-NR2B9C, histidine and trehalose |
| US10191033B2 (en) | 2013-12-05 | 2019-01-29 | The Broad Institute, Inc. | Biomarkers for detecting pre-cachexia or cachexia and methods of treatment thereof |
| WO2016051808A1 (ja) * | 2014-10-01 | 2016-04-07 | 国立研究開発法人農業・食品産業技術総合研究機構 | 遺伝子組換えカイコにより生産したビオチン化酸化ｌｄｌ受容体・終末糖化産物受容体 |
| EP3307781B8 (en) | 2015-06-10 | 2020-12-02 | The Broad Institute, Inc. | Antibodies, compounds and screens for identifying and treating cachexia or pre-cachexia |
| WO2017106196A1 (en) | 2015-12-14 | 2017-06-22 | The Broad Institute, Inc. | Compositions and methods for treating cardiac dysfunction |
| CN112699601B (zh) * | 2020-12-28 | 2022-05-31 | 电子科技大学 | 一种传感器网络数据的空时重构方法 |
| US20230246158A1 (en) * | 2022-02-02 | 2023-08-03 | Enevate Corporation | Cycle life in si/li batteries using high temperature deep discharge cycling |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5567677A (en) * | 1992-04-03 | 1996-10-22 | Pharmacia Ab | Protein formulation comprising growth hormone |
| US6267958B1 (en) * | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| WO2006017643A1 (en) * | 2004-08-03 | 2006-02-16 | Transtech Pharma, Inc. | Rage fusion proteins and methods of use |
Family Cites Families (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4867973A (en) | 1984-08-31 | 1989-09-19 | Cytogen Corporation | Antibody-therapeutic agent conjugates |
| US6018026A (en) | 1988-01-22 | 2000-01-25 | Zymogenetics, Inc. | Biologically active dimerized and multimerized polypeptide fusions |
| US5567584A (en) | 1988-01-22 | 1996-10-22 | Zymogenetics, Inc. | Methods of using biologically active dimerized polypeptide fusions to detect PDGF |
| NZ235148A (en) | 1989-09-05 | 1991-12-23 | Immunex Corp | Tumour necrosis factor receptor protein and dna sequences |
| MX9204374A (es) | 1991-07-25 | 1993-03-01 | Idec Pharma Corp | Anticuerpo recombinante y metodo para su produccion. |
| JP3589665B2 (ja) | 1992-10-23 | 2004-11-17 | イミュネックス・コーポレーション | 可溶性オリゴマー蛋白質の調製法 |
| US5656261A (en) | 1995-01-18 | 1997-08-12 | The Picower Institute For Medical Research | Preventing and reversing advanced glycosylation endproducts |
| FI119756B (fi) | 1995-01-18 | 2009-03-13 | Alteon Inc | Tiatsoliumyhdisteiden käyttö pitkälle edenneen glykosylaation lopputuotteiden muodostumisen estossa ja suunnan muutoksessa |
| CA2210684C (en) | 1995-01-18 | 2008-01-15 | Alteon Inc. | Use of thiazolium compounds for preventing and reversing the formation of advanced glycosylation endproducts |
| AU5386996A (en) | 1995-04-05 | 1996-10-23 | Picower Institute For Medical Research, The | Agents for binding to advanced glycosylation endproducts, an d methods of their use |
| US5747035A (en) | 1995-04-14 | 1998-05-05 | Genentech, Inc. | Polypeptides with increased half-life for use in treating disorders involving the LFA-1 receptor |
| WO1997026913A1 (en) | 1996-01-26 | 1997-07-31 | The Trustees Of Columbia University In The City Of New York | A POLYPEPTIDE FROM LUNG EXTRACT WHICH BINDS AMYLOID-β PEPTIDE |
| WO1997039121A1 (en) | 1996-04-16 | 1997-10-23 | Schering Aktiengesellschaft | Advanced glycosylation end-product receptor peptides and uses therefor |
| US5864018A (en) | 1996-04-16 | 1999-01-26 | Schering Aktiengesellschaft | Antibodies to advanced glycosylation end-product receptor polypeptides and uses therefor |
| US7258857B2 (en) | 1996-11-22 | 2007-08-21 | The Trustees Of Columbia University In The City Of New York | Rage-related methods for treating inflammation |
| WO2000020621A1 (en) | 1998-10-06 | 2000-04-13 | The Trustees Of Columbia University In The City Of New York | Extracellular novel rage binding protein (en-rage) and uses thereof |
| US6555651B2 (en) | 1997-10-09 | 2003-04-29 | The Trustees Of Columbia University In The City Of New York | Ligand binding site of rage and uses thereof |
| US6790443B2 (en) | 1996-11-22 | 2004-09-14 | The Trustees Of Columbia University In The City Of New York | Method for treating symptoms of diabetes |
| US7081241B1 (en) | 1998-10-06 | 2006-07-25 | The Trustees Of Columbia University In The City Of New York | Extracellular rage binding protein (EN-RAGE) and uses thereof |
| AU748768B2 (en) | 1997-03-11 | 2002-06-13 | General Hospital Corporation, The | Identification of agents for use in the treatment of Alzheimer's disease |
| US7101838B2 (en) | 1997-08-05 | 2006-09-05 | The Trustees Of Columbia University In The City Of New York | Method to prevent accelerated atherosclerosis using (sRAGE) soluble receptor for advanced glycation endproducts |
| MY131805A (en) * | 1997-09-18 | 2007-09-28 | Biogen Idec Inc | Synergistic composition and methods for treating neoplastic or cancerous growths and for restoring or boosting hematopoiesis. |
| US6380165B1 (en) | 1997-09-19 | 2002-04-30 | The Picower Institute For Medical Research | Immunological advanced glycation endproduct crosslink |
| US6761888B1 (en) | 2000-05-26 | 2004-07-13 | Neuralab Limited | Passive immunization treatment of Alzheimer's disease |
| US6323218B1 (en) | 1998-03-11 | 2001-11-27 | The General Hospital Corporation | Agents for use in the treatment of Alzheimer's disease |
| US20020102604A1 (en) | 1999-12-08 | 2002-08-01 | Milne Edwards Jean-Baptiste Dumas | Full-length human cDNAs encoding potentially secreted proteins |
| US6465422B1 (en) | 1998-04-17 | 2002-10-15 | The Trustees Of Columbia University In The City Of New York | Method for inhibiting tumor invasion or spreading in a subject |
| US6706683B1 (en) | 1998-09-29 | 2004-03-16 | Asahi Kasei Pharma Corporation | Method for controlling the release of granules |
| US6753150B2 (en) | 1998-10-05 | 2004-06-22 | The Trustees Of Columbia University In The City Of New York | Method for determining whether a compound is capable of inhibiting the interaction of a peptide with rage |
| DE69918146T2 (de) * | 1998-10-05 | 2005-07-07 | Pharmexa A/S | Verfahren zur therapeutischen impfung |
| US6197294B1 (en) | 1998-10-26 | 2001-03-06 | Neurotech S.A. | Cell surface molecule-induced macrophage activation |
| US6589944B1 (en) | 1999-04-05 | 2003-07-08 | City Of Hope | Breakers of advanced glycation endproducts |
| US6605642B2 (en) | 1999-04-05 | 2003-08-12 | City Of Hope | Inhibitors of formation of advanced glycation endproducts (AGES) |
| US6787566B2 (en) | 1999-04-05 | 2004-09-07 | City Of Hope | Breakers of advanced glycation endproducts |
| US6939545B2 (en) | 1999-04-28 | 2005-09-06 | Genetics Institute, Llc | Composition and method for treating inflammatory disorders |
| US6835200B2 (en) | 1999-06-22 | 2004-12-28 | Ndo Surgical. Inc. | Method and devices for tissue reconfiguration |
| FR2797402B1 (fr) | 1999-07-15 | 2004-03-12 | Biomerieux Stelhys | Utilisation d'un polypeptide pour detecter, prevenir ou traiter un etat pathologique associe a une maladie degenerative, neurologique ou autoimmune |
| CA2382095A1 (en) | 1999-08-13 | 2001-02-22 | The Trustees Of Columbia University In The City Of New York | Methods of inhibiting binding of .beta.-sheet fibril to rage and consequences thereof |
| WO2001018060A1 (fr) | 1999-09-08 | 2001-03-15 | Toray Industries, Inc. | Materiaux de circulation extracorporelle, adsorbants de facteurs de complication diabetique, reservoirs servant a eliminer des facteurs de complication diabetique et procede d'elimination de facteurs de complication diabetique |
| US20050170382A1 (en) | 1999-10-06 | 2005-08-04 | The Trustees Of Columbia University In The City Of New York. | RAGE-related compositions |
| EP1287162A2 (en) | 1999-10-21 | 2003-03-05 | Case Western Reserve University | Gene expression profiling of inflammatory bowel disease |
| PT1272843E (pt) | 2000-04-14 | 2007-10-01 | Niadyne Corp | Método para identificação de reguladores da formação de age de proteínas |
| US20010041349A1 (en) | 2000-04-17 | 2001-11-15 | Andrew Patron | Protein expression system arrays and use in biological screening |
| US6825164B1 (en) | 2000-08-14 | 2004-11-30 | The Trustees Of Columbia University In The City Of New York | Method to increase cerebral blood flow in amyloid angiopathy |
| US6563015B1 (en) | 2000-08-14 | 2003-05-13 | The Trustees Of Columbia University In The City Of New York | Transgenic mice over-expressing receptor for advanced glycation endproduct (RAGE) and mutant APP in brain and uses thereof |
| AU2001296959A1 (en) | 2000-10-02 | 2002-04-15 | Reddy Us Therapeutics, Inc | Methods and compositions for the treatment of inflammatory diseases |
| WO2002030889A2 (en) | 2000-10-13 | 2002-04-18 | The Trustees Of Columbia University In The City Of New York | A method for inhibiting new tissue growth in blood vessels in a patient subjected to blood vessel injury |
| US20050244849A1 (en) | 2000-12-15 | 2005-11-03 | Genetics Institute, Llc | Screening assays for rheumatoid arthritis |
| BR0116606A (pt) | 2000-12-29 | 2006-05-09 | Reddy Us Therapeutics Inc | métodos e composições para detecção de compostos que modulam as respostas inflamatórias |
| AU2002233340B2 (en) | 2001-02-19 | 2008-05-22 | Merck Patent Gmbh | Artificial fusion proteins with reduced immunogenicity |
| JP3837494B2 (ja) | 2001-03-19 | 2006-10-25 | 国立大学法人金沢大学 | 可溶型ｒａｇｅタンパク質 |
| US7304034B2 (en) | 2001-05-15 | 2007-12-04 | The Feinstein Institute For Medical Research | Use of HMGB fragments as anti-inflammatory agents |
| CN1774445A (zh) | 2002-08-16 | 2006-05-17 | 惠氏公司 | 用于治疗rage相关病症的组合物和方法 |
| WO2004100890A2 (en) | 2003-05-09 | 2004-11-25 | The Trustees Of Columbia University In The City Of New York | Rage g82s-related methods and compositions for treating inflammatory disorders |
| US20050008649A1 (en) | 2003-06-02 | 2005-01-13 | University Of Miami | Chimeric molecules and methods of use |
| JP2007504247A (ja) | 2003-09-05 | 2007-03-01 | ザ・トラスティーズ・オブ・コランビア・ユニバーシティー・イン・ザ・シティー・オブ・ニューヨーク | 糸球体損傷を治療するためのｒａｇｅに関連した方法および組成物 |
| US20070167360A1 (en) | 2003-10-31 | 2007-07-19 | Yan Shi D | Methods for treating multiple sclerosis |
| US20060012414A1 (en) * | 2004-07-15 | 2006-01-19 | Texas Instruments Incorporated | Circuit and method for generating a polyphase clock signal and system incorporating the same |
| US7470521B2 (en) | 2004-07-20 | 2008-12-30 | Critical Therapeutics, Inc. | RAGE protein derivatives |
| WO2006012414A2 (en) | 2004-07-20 | 2006-02-02 | Critical Therapeutics, Inc. | Novel polyadenylation signal for use in expression vectors |
| MX2007001559A (es) * | 2004-08-03 | 2007-04-10 | Transtech Pharma Inc | Proteinas de fusion de receptor para productos finales glicados avanzados y metodos de uso. |
| CA2581505A1 (en) | 2004-09-27 | 2006-04-06 | Centocor, Inc. | Srage mimetibody, compositions, methods and uses |
| US20080207499A1 (en) | 2005-06-29 | 2008-08-28 | Gaetano Barile | Rage-related methods for treating and preventing diabetic retinopathy |
| CN101410411A (zh) * | 2006-02-09 | 2009-04-15 | 转化技术制药公司 | Rage融合蛋白及使用方法 |
| SG171670A1 (en) | 2006-05-05 | 2011-06-29 | Transtech Pharma Inc | Rage fusion proteins, formulations, and methods of use thereof |
| WO2008100470A2 (en) | 2007-02-15 | 2008-08-21 | Transtech Pharma, Inc. | Rage - immunoglobulin fusion proteins |
-
2007
- 2007-04-25 SG SG201103296-8A patent/SG171670A1/en unknown
- 2007-04-25 MX MX2008013863A patent/MX2008013863A/es active IP Right Grant
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- 2007-04-25 BR BRPI0711193-2A patent/BRPI0711193A2/pt not_active IP Right Cessation
- 2007-04-25 US US11/789,637 patent/US7981424B2/en not_active Expired - Fee Related
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- 2007-04-25 AU AU2007248784A patent/AU2007248784B2/en not_active Ceased
- 2007-04-25 KR KR1020087029731A patent/KR20090008459A/ko not_active Withdrawn
- 2007-04-25 CA CA002651348A patent/CA2651348A1/en not_active Abandoned
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5567677A (en) * | 1992-04-03 | 1996-10-22 | Pharmacia Ab | Protein formulation comprising growth hormone |
| US6267958B1 (en) * | 1995-07-27 | 2001-07-31 | Genentech, Inc. | Protein formulation |
| WO2006017643A1 (en) * | 2004-08-03 | 2006-02-16 | Transtech Pharma, Inc. | Rage fusion proteins and methods of use |
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| WO2007130302A2 (en) | 2007-11-15 |
| US20080045455A1 (en) | 2008-02-21 |
| AR060862A1 (es) | 2008-07-16 |
| IL194482A0 (en) | 2011-08-01 |
| CN101548012A (zh) | 2009-09-30 |
| EA017291B1 (ru) | 2012-11-30 |
| ZA200809394B (en) | 2009-07-29 |
| DOP2007000089A (es) | 2007-11-15 |
| MX2008013863A (es) | 2008-11-14 |
| US7981424B2 (en) | 2011-07-19 |
| JP2009536201A (ja) | 2009-10-08 |
| SG171670A1 (en) | 2011-06-29 |
| JP5558810B2 (ja) | 2014-07-23 |
| BRPI0711193A2 (pt) | 2013-06-18 |
| PE20080397A1 (es) | 2008-04-28 |
| EP2380983A2 (en) | 2011-10-26 |
| TW200801036A (en) | 2008-01-01 |
| EP2021474A2 (en) | 2009-02-11 |
| US20110282035A1 (en) | 2011-11-17 |
| WO2007130302A3 (en) | 2008-04-03 |
| KR20090008459A (ko) | 2009-01-21 |
| EP2380983A3 (en) | 2012-12-05 |
| UY30324A1 (es) | 2008-01-02 |
| NL2000626A1 (nl) | 2007-11-06 |
| EA200870502A1 (ru) | 2009-06-30 |
| AU2007248784A1 (en) | 2007-11-15 |
| NZ571692A (en) | 2012-01-12 |
| US8344120B2 (en) | 2013-01-01 |
| CA2651348A1 (en) | 2007-11-15 |
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