ES2207759T3 - Terapia de combinacion que utiliza una proteina de union del factor de necrosis tumoral (tnf) en el tratamiento de enfermedades inducidas por el tnf. - Google Patents
Terapia de combinacion que utiliza una proteina de union del factor de necrosis tumoral (tnf) en el tratamiento de enfermedades inducidas por el tnf.Info
- Publication number
- ES2207759T3 ES2207759T3 ES97953156T ES97953156T ES2207759T3 ES 2207759 T3 ES2207759 T3 ES 2207759T3 ES 97953156 T ES97953156 T ES 97953156T ES 97953156 T ES97953156 T ES 97953156T ES 2207759 T3 ES2207759 T3 ES 2207759T3
- Authority
- ES
- Spain
- Prior art keywords
- amino acid
- sequence
- seq
- tnf
- tnf binding
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
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- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/177—Receptors; Cell surface antigens; Cell surface determinants
- A61K38/1793—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
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- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
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| US6277969B1 (en) * | 1991-03-18 | 2001-08-21 | New York University | Anti-TNF antibodies and peptides of human tumor necrosis factor |
| US20040120952A1 (en) * | 2000-08-07 | 2004-06-24 | Centocor, Inc | Anti-TNF antibodies and peptides of human tumor necrosis factor |
| US7192584B2 (en) * | 1991-03-18 | 2007-03-20 | Centocor, Inc. | Methods of treating psoriasis with anti-TNF antibodies |
| US6270766B1 (en) | 1992-10-08 | 2001-08-07 | The Kennedy Institute Of Rheumatology | Anti-TNF antibodies and methotrexate in the treatment of arthritis and crohn's disease |
| US6770279B1 (en) | 1992-10-08 | 2004-08-03 | The Kennedy Institute Of Rheumatology | TNFα antagonists and cyclosporin in therapy of rheumatoid arthritis |
| US7091181B2 (en) | 1994-12-12 | 2006-08-15 | Omeros Corporation | Method of inhibition of pain and inflammation during surgery comprising administration of soluble TNF receptors |
| US20040127884A1 (en) * | 1994-12-12 | 2004-07-01 | Omeros Corporation | Vascular irrigation solution and method for inhibition of pain, inflammation, spasm and restenosis |
| AU4467396A (en) | 1994-12-12 | 1996-07-10 | Omeros Medical Systems, Inc. | Irrigation solution and method for inhibition of pain, inflammation and spasm |
| US20020028798A1 (en) * | 1995-12-12 | 2002-03-07 | Omeros Medical Systems | Irrigation solution and method for inhibition of pain and inflammation |
| US7067144B2 (en) * | 1998-10-20 | 2006-06-27 | Omeros Corporation | Compositions and methods for systemic inhibition of cartilage degradation |
| AU1521000A (en) * | 1998-11-06 | 2000-05-29 | Schepens Eye Research Institute, Inc., The | Local use of soluble tumor necrosis receptor i (stnfri) for prophylaxis and treatment of corneal transplant rejection and other disorders of the eye |
| US8119127B2 (en) * | 1999-02-24 | 2012-02-21 | Tact Ip, Llc | Cytokine antagonists for neurological and neuropsychiatric disorders |
| US6982089B2 (en) * | 1999-02-24 | 2006-01-03 | Tact Ip, Llc | Cytokine antagonists for neurological and neuropsychiatric disorders |
| USRE45976E1 (en) * | 1999-02-24 | 2016-04-19 | Tact Ip, Llc | Methods of inhibiting the action of TNF for neurological conditions by administering etanercept intrathecally |
| CA2366785C (en) * | 1999-04-19 | 2012-02-07 | Immunex Corporation | Soluble tumor necrosis factor receptor treatment of medical disorders |
| US20040220103A1 (en) * | 1999-04-19 | 2004-11-04 | Immunex Corporation | Soluble tumor necrosis factor receptor treatment of medical disorders |
| US6537540B1 (en) * | 1999-05-28 | 2003-03-25 | Targeted Genetics Corporation | Methods and composition for lowering the level of tumor necrosis factor (TNF) in TNF-associated disorders |
| CN1402642A (zh) * | 1999-07-21 | 2003-03-12 | 奥默罗斯公司 | 用于抑制疼痛,炎症和软骨退化的溶液及方法 |
| EP1237575B1 (en) * | 1999-12-14 | 2008-08-06 | Genentech, Inc. | Tnf-alpha antagonist and lfa-1 antagonist for treating rheumatoid arthritis |
| US7244823B2 (en) * | 2000-03-02 | 2007-07-17 | Xencor | TNF-alpha variants proteins for the treatment of TNF-alpha related disorders |
| US20070172449A1 (en) * | 2000-03-02 | 2007-07-26 | Xencor, Inc. | TNF-alpha VARIANT FORMULATIONS FOR THE TREATMENT OF TNF-alpha RELATED DISORDERS |
| US7687461B2 (en) * | 2000-03-02 | 2010-03-30 | Xencor, Inc. | Treatment of TNF-α related disorders with TNF-α variant proteins |
| CA2408408C (en) | 2000-05-12 | 2013-07-09 | Genzyme Corporation | Modulators of tnf- alpha signaling |
| EP1309328A4 (en) * | 2000-06-20 | 2006-02-08 | Arthur L Herbst | COX-2 INHIBITORS AND PREVENTING THE SIDE EFFECTS OF IRRADIATION THERAPY |
| US20060018907A1 (en) * | 2000-08-07 | 2006-01-26 | Centocor, Inc. | Anti-TNF antibodies and peptides of human tumor necrosis factor |
| WO2002017853A2 (en) * | 2000-08-31 | 2002-03-07 | Genzyme Biosurgery Corporation | Hyaluronan-based antiadhesion compositions, their preparation and use |
| US7087224B2 (en) * | 2000-10-31 | 2006-08-08 | Amgen Inc. | Method of treating anemia by administering IL-1ra |
| TR201809678T4 (tr) | 2001-06-26 | 2018-07-23 | Amgen Fremont Inc | Opgl ye karşi antikorlar. |
| DE10132308A1 (de) * | 2001-07-06 | 2003-01-30 | Aventis Behring Gmbh | Kombinationspräparat zur Therapie von immunologischen Erkrankungen |
| US7084257B2 (en) | 2001-10-05 | 2006-08-01 | Amgen Inc. | Fully human antibody Fab fragments with human interferon-gamma neutralizing activity |
| AU2003282955A1 (en) * | 2002-10-17 | 2004-05-04 | Alkermes Controlled Therapeutics, Inc. Ii | Microencapsulation and sustained release of biologically active polypeptides |
| DE60335652D1 (de) * | 2002-11-21 | 2011-02-17 | Genzyme Corp | Verwendung eines diamidderivats zur verhinderung der chronischen transplantatabstossung |
| AU2003291143A1 (en) * | 2002-11-21 | 2004-06-18 | Genzyme Corporation | Combination of diamide derivatives and immunosuppressive agents for induction of immune tolerance |
| EA009079B1 (ru) | 2003-02-28 | 2007-10-26 | Арес Трейдинг С.А. | Жидкие составы фактор некроза опухоли-связывающих белков |
| WO2005000227A2 (en) * | 2003-06-06 | 2005-01-06 | Intermune, Inc. | Methods of treating tnf-mediated disorders |
| CN1968700A (zh) * | 2004-04-15 | 2007-05-23 | 阿尔克姆斯有限公司 | 聚合物基的持续释放装置 |
| US7456254B2 (en) * | 2004-04-15 | 2008-11-25 | Alkermes, Inc. | Polymer-based sustained release device |
| ES2309817T3 (es) | 2004-12-02 | 2008-12-16 | Can-Fite Biopharma Ltd. | Tratamiento de inflamacion. |
| US20080051365A1 (en) * | 2004-12-02 | 2008-02-28 | Can-Fite Biopharma Ltd. | Treatment of Inflammation |
| US8236306B2 (en) * | 2004-12-18 | 2012-08-07 | Edward Lewis Tobinick | Methods to facilitate transmission of large molecules across the blood-brain, blood-eye, and blood-nerve barriers |
| US20060205682A1 (en) * | 2005-02-25 | 2006-09-14 | Roberts Richard H | Antibiotic and combinations of antibiotic and symptomatic relief agent formulations |
| AR056806A1 (es) | 2005-11-14 | 2007-10-24 | Amgen Inc | Moleculas quimericas de anticuerpo rankl- pth/ pthrp |
| US20080118496A1 (en) * | 2006-04-10 | 2008-05-22 | Medich John R | Uses and compositions for treatment of juvenile rheumatoid arthritis |
| EP2171451A4 (en) | 2007-06-11 | 2011-12-07 | Abbott Biotech Ltd | METHOD FOR TREATING JUVENILIAN IDIOPATHIC ARTHRITIS |
| EP2507267B1 (en) * | 2009-12-02 | 2016-09-14 | Acceleron Pharma, Inc. | Compositions and methods for increasing serum half-life of fc fusion proteins |
| US8883982B2 (en) | 2011-06-08 | 2014-11-11 | Acceleron Pharma, Inc. | Compositions and methods for increasing serum half-life |
| CN103965357B (zh) | 2013-12-31 | 2016-08-17 | 嘉和生物药业有限公司 | 一种抗人rankl抗体 |
| EP3085709B1 (en) | 2014-12-28 | 2019-08-21 | Genor Biopharma Co., Ltd | Humanized anti-human rankl antibody, pharmaceutical composition and use thereof |
Family Cites Families (49)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US4179337A (en) | 1973-07-20 | 1979-12-18 | Davis Frank F | Non-immunogenic polypeptides |
| IN150740B (enExample) | 1978-11-24 | 1982-12-04 | Hoffmann La Roche | |
| US4959314A (en) | 1984-11-09 | 1990-09-25 | Cetus Corporation | Cysteine-depleted muteins of biologically active proteins |
| US4766106A (en) | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
| US4917888A (en) | 1985-06-26 | 1990-04-17 | Cetus Corporation | Solubilization of immunotoxins for pharmaceutical compositions using polymer conjugation |
| US4935233A (en) | 1985-12-02 | 1990-06-19 | G. D. Searle And Company | Covalently linked polypeptide cell modulators |
| IL80005A (en) | 1986-09-10 | 1992-11-15 | Yeda Res & Dev | Compositions for modulating the effect of tnf and il-1 |
| IL90339A (en) | 1989-05-18 | 1996-10-16 | Yeda Res & Dev | Anti-cytotoxic protein and its purification |
| IL83878A (en) | 1987-09-13 | 1995-07-31 | Yeda Res & Dev | Soluble protein corresponding to tnf inhibitory protein its preparation and pharmaceutical compositions containing it |
| IL98078A0 (en) | 1991-05-07 | 1992-06-21 | Yeda Res & Dev | Pharmaceutical compositions comprising an anticytokyne |
| US5512544A (en) | 1987-09-13 | 1996-04-30 | Yeda Research And Development Co. Ltd. | Pharmaceutical compositions comprising an anticytokine |
| US5153265A (en) | 1988-01-20 | 1992-10-06 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
| US4847325A (en) | 1988-01-20 | 1989-07-11 | Cetus Corporation | Conjugation of polymer to colony stimulating factor-1 |
| GB8806339D0 (en) | 1988-03-17 | 1988-04-13 | Hoffmann La Roche | Monoclonal antibodies |
| GB8807803D0 (en) | 1988-03-31 | 1988-05-05 | Glaxo Group Ltd | Biochemical product |
| IL94039A (en) | 1989-08-06 | 2006-09-05 | Yeda Res & Dev | Antibodies to tbp - 1 and their use |
| US5359037A (en) | 1988-09-12 | 1994-10-25 | Yeda Research And Development Co. Ltd. | Antibodies to TNF binding protein I |
| US5811261A (en) | 1988-09-12 | 1998-09-22 | Yeda Research And Development Co. Ltd. | Expression of the recombinant tumor necrosis factor binding protein I (TBP-I) |
| AU4660789A (en) | 1988-11-23 | 1990-06-12 | Genentech Inc. | Polypeptide derivatives |
| US5116964A (en) | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
| US5122614A (en) | 1989-04-19 | 1992-06-16 | Enzon, Inc. | Active carbonates of polyalkylene oxides for modification of polypeptides |
| US5166322A (en) | 1989-04-21 | 1992-11-24 | Genetics Institute | Cysteine added variants of interleukin-3 and chemical modifications thereof |
| DE3922089A1 (de) | 1989-05-09 | 1990-12-13 | Basf Ag | Neue proteine und ihre herstellung |
| AU636608B2 (en) | 1989-05-18 | 1993-05-06 | Yeda Research And Development Co. Ltd. | Tumor necrosis factor binding protein II, it's purification and antibodies thereto |
| IL95031A (en) | 1989-07-18 | 2007-03-08 | Amgen Inc | Method for the production of a human recombinant tumor necrosis factor inhibitor |
| US5605690A (en) | 1989-09-05 | 1997-02-25 | Immunex Corporation | Methods of lowering active TNF-α levels in mammals using tumor necrosis factor receptor |
| CA2065346C (en) | 1989-09-05 | 2005-03-29 | Craig A. Smith | Tumor necrosis factor-.alpha. and-.beta. receptors |
| NZ235148A (en) | 1989-09-05 | 1991-12-23 | Immunex Corp | Tumour necrosis factor receptor protein and dna sequences |
| US5395760A (en) | 1989-09-05 | 1995-03-07 | Immunex Corporation | DNA encoding tumor necrosis factor-α and -β receptors |
| DE59010908D1 (de) | 1989-09-12 | 2000-08-10 | Hoffmann La Roche | TNF-bindende Proteine |
| ES2080098T3 (es) | 1989-12-13 | 1996-02-01 | Yeda Res & Dev | Expresion de la proteina de union i al factor de necrosis tumoral tbp-i recombinante. |
| US5136021A (en) | 1990-02-27 | 1992-08-04 | Health Research, Inc. | TNF-inhibitory protein and a method of production |
| US6552170B1 (en) | 1990-04-06 | 2003-04-22 | Amgen Inc. | PEGylation reagents and compounds formed therewith |
| GB2246569A (en) | 1990-06-15 | 1992-02-05 | Charing Cross Sunley Research | Tumour necrosis factor - alpha binding protein |
| WO1992001002A1 (en) | 1990-07-11 | 1992-01-23 | Teijin Limited | Tumor necrosis factor activity inhibitor and production thereof |
| GB9015908D0 (en) | 1990-07-19 | 1990-09-05 | Celltech Ltd | Multivalent immunoglobulin |
| GB9022648D0 (en) | 1990-10-18 | 1990-11-28 | Charing Cross Sunley Research | Polypeptide and its use |
| GB9023783D0 (en) * | 1990-11-01 | 1990-12-12 | Celltech Ltd | Pharmaceutical product |
| US5252714A (en) | 1990-11-28 | 1993-10-12 | The University Of Alabama In Huntsville | Preparation and use of polyethylene glycol propionaldehyde |
| GEP20002142B (en) | 1991-01-18 | 2000-06-25 | Amgen Inc | Method for Treatment and Prevention of TNF Mediated Diseases |
| AU1674292A (en) | 1991-03-15 | 1992-10-21 | Synergen, Inc. | Pegylation of polypeptides |
| WO1993001498A1 (en) | 1991-07-04 | 1993-01-21 | Immunodex K/S | Water-soluble, polymer-based reagents and conjugates comprising moieties derived from divinyl sulfone |
| IL99120A0 (en) | 1991-08-07 | 1992-07-15 | Yeda Res & Dev | Multimers of the soluble forms of tnf receptors,their preparation and pharmaceutical compositions containing them |
| NZ256293A (en) * | 1992-09-15 | 1997-06-24 | Immunex Corp | Method of treating tumour necrosis factor - mediated inflammation by use of tnf antagonist |
| US6270766B1 (en) * | 1992-10-08 | 2001-08-07 | The Kennedy Institute Of Rheumatology | Anti-TNF antibodies and methotrexate in the treatment of arthritis and crohn's disease |
| US5446090A (en) | 1993-11-12 | 1995-08-29 | Shearwater Polymers, Inc. | Isolatable, water soluble, and hydrolytically stable active sulfones of poly(ethylene glycol) and related polymers for modification of surfaces and molecules |
| US5723116A (en) * | 1995-01-06 | 1998-03-03 | University Of South Florida | Decreased mortality of severe acute pancreatitis following proximal cytokine blockade |
| US6096728A (en) * | 1996-02-09 | 2000-08-01 | Amgen Inc. | Composition and method for treating inflammatory diseases |
| US5747639A (en) | 1996-03-06 | 1998-05-05 | Amgen Boulder Inc. | Use of hydrophobic interaction chromatography to purify polyethylene glycols |
-
1997
- 1997-12-08 AT AT97953156T patent/ATE247974T1/de active
- 1997-12-08 DK DK97953156T patent/DK0942740T3/da active
- 1997-12-08 WO PCT/US1997/022733 patent/WO1998024463A2/en not_active Ceased
- 1997-12-08 AU AU56961/98A patent/AU5696198A/en not_active Abandoned
- 1997-12-08 JP JP52589398A patent/JP2001513754A/ja not_active Ceased
- 1997-12-08 EP EP97953156A patent/EP0942740B1/en not_active Expired - Lifetime
- 1997-12-08 CA CA002273850A patent/CA2273850A1/en not_active Abandoned
- 1997-12-08 PT PT97953156T patent/PT942740E/pt unknown
- 1997-12-08 ES ES97953156T patent/ES2207759T3/es not_active Expired - Lifetime
- 1997-12-08 DE DE69724451T patent/DE69724451T2/de not_active Expired - Lifetime
-
1999
- 1999-06-04 US US09/326,394 patent/US6306820B1/en not_active Expired - Fee Related
-
2001
- 2001-07-17 US US09/907,263 patent/US20020119924A1/en not_active Abandoned
-
2003
- 2003-07-16 US US10/622,383 patent/US20040048799A1/en not_active Abandoned
- 2003-07-16 US US10/621,783 patent/US20040047863A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP0942740B1 (en) | 2003-08-27 |
| DE69724451D1 (de) | 2003-10-02 |
| CA2273850A1 (en) | 1998-06-11 |
| EP0942740A2 (en) | 1999-09-22 |
| DE69724451T2 (de) | 2004-03-18 |
| ATE247974T1 (de) | 2003-09-15 |
| HK1022440A1 (en) | 2000-08-11 |
| WO1998024463A2 (en) | 1998-06-11 |
| US6306820B1 (en) | 2001-10-23 |
| AU5696198A (en) | 1998-06-29 |
| JP2001513754A (ja) | 2001-09-04 |
| PT942740E (pt) | 2004-01-30 |
| US20040048799A1 (en) | 2004-03-11 |
| WO1998024463A3 (en) | 1998-07-16 |
| US20040047863A1 (en) | 2004-03-11 |
| US20020119924A1 (en) | 2002-08-29 |
| DK0942740T3 (da) | 2003-12-15 |
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