JP4271850B2 - Ｉｌ−１８受容体 - Google Patents
Ｉｌ−１８受容体 Download PDFInfo
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- JP4271850B2 JP4271850B2 JP2000528679A JP2000528679A JP4271850B2 JP 4271850 B2 JP4271850 B2 JP 4271850B2 JP 2000528679 A JP2000528679 A JP 2000528679A JP 2000528679 A JP2000528679 A JP 2000528679A JP 4271850 B2 JP4271850 B2 JP 4271850B2
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- polypeptide
- 1rrp1
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| US6927044B2 (en) | 1998-09-25 | 2005-08-09 | Regeneron Pharmaceuticals, Inc. | IL-1 receptor based cytokine traps |
| US20020155526A1 (en) | 1998-09-30 | 2002-10-24 | Busfield Samantha J. | Novel secreted immunomodulatory proteins and uses thereof |
| US6610286B2 (en) | 1999-12-23 | 2003-08-26 | Zymogenetics, Inc. | Method for treating inflammation using soluble receptors to interleukin-20 |
| JP4741139B2 (ja) * | 1999-12-23 | 2011-08-03 | ザイモジェネティクス， インコーポレイテッド | 可溶性インターロイキン−２０レセプター |
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| US20020025317A1 (en) * | 2000-07-20 | 2002-02-28 | Schering Ag | Bispecific monoclonal antibodies to IL-12 and IL-18 |
| US20020052475A1 (en) * | 2000-07-20 | 2002-05-02 | Schering Ag | High affinity soluble interleukin-18 receptor |
| ES2381650T3 (es) | 2000-08-08 | 2012-05-30 | Zymogenetics, Inc. | Receptores de citoquinas Zcytor11 solubles |
| JP4908723B2 (ja) | 2000-09-15 | 2012-04-04 | ザイモジェネティクス， インコーポレイテッド | 炎症を治療するための方法 |
| CA2424983A1 (en) | 2000-10-11 | 2002-04-18 | Viron Therapeutics, Inc. | Nucleic acid molecules and polypeptides for immune modulation |
| US7718368B2 (en) * | 2000-12-04 | 2010-05-18 | Viron Therapeutics Inc. | Immunomodulatory protein and useful embodiments thereof |
| GB2375604A (en) * | 2001-05-18 | 2002-11-20 | Warner Lambert Co | Methods for screening using interleukin soluble trimolecular complex |
| PH12012502440A1 (en) | 2001-06-26 | 2013-06-17 | Amgen Inc | Antibodies to opgl |
| EP1293566A1 (en) * | 2001-09-17 | 2003-03-19 | Societe Des Produits Nestle S.A. | A soluble toll-like receptor |
| CA2467723C (en) | 2001-12-17 | 2011-09-27 | Zymogenetics, Inc. | Method for treating cervical cancer |
| AU2003259995B2 (en) | 2002-08-28 | 2009-07-02 | Immunex Corporation | Compositions and methods for treating cardiovascular disease |
| MXPA05003869A (es) | 2002-10-08 | 2005-06-22 | Ares Trading Sa | El uso de citocina capaz de enlazarse a la proteina de union a interleucina-18, y de inhibir la actividad de una segunda citocina. |
| EP1606316A2 (en) | 2003-03-24 | 2005-12-21 | ZymoGenetics, Inc. | Anti-il-20 antibodies and binding partners and methods of using in inflammation |
| TWI353991B (en) | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
| US20050100965A1 (en) | 2003-11-12 | 2005-05-12 | Tariq Ghayur | IL-18 binding proteins |
| US7968684B2 (en) * | 2003-11-12 | 2011-06-28 | Abbott Laboratories | IL-18 binding proteins |
| DE602004023965D1 (de) | 2003-11-21 | 2009-12-17 | Zymogenetics Inc | Anti-il-20-antikörper und bindungspartner und verfahren zur anwendung bei entzündungen |
| US7141382B1 (en) | 2004-10-12 | 2006-11-28 | Parikh Chirag R | Methods for detection of IL-18 as an early marker for diagnosis of acute renal failure and predictor of mortality |
| JP4898691B2 (ja) | 2004-10-22 | 2012-03-21 | ザイモジェネティクス， インコーポレイテッド | 抗ｉｌ−２２ｒａ抗体および結合パートナー、ならびに炎症における使用法 |
| AU2005327508A1 (en) * | 2005-02-15 | 2006-08-24 | Apollo Life Sciences Limited | Molecules and chimeric molecules thereof |
| JP2009527535A (ja) * | 2006-02-22 | 2009-07-30 | ユニバーシティ オブ チューリッヒ | 自己免疫疾患又は脱髄疾患を処置するための可溶性受容体及び方法 |
| JP5368301B2 (ja) | 2006-06-22 | 2013-12-18 | ノボ・ノルデイスク・エー／エス | 可溶性ヘテロ二量体レセプター及びその使用 |
| MX2009012343A (es) * | 2007-05-14 | 2010-02-10 | Biogen Idec Inc | Regiones fc (sc fc) de cadena sencilla, polipeptidos de enlace que comprenden las mismas, y metodos relacionados con ello. |
| CL2008002153A1 (es) | 2007-07-24 | 2009-06-05 | Amgen Inc | Anticuerpo aislado o fragmanto de unión de antigeno del mismo que se une al receptor de il-18 (il-18r); molecula de ácido nucleico codificante; celula huesped que la comprende; composición farmaceutica; uso médico para tratar o prevenir una condición asociada con il-18r; método in vitro para inhibir la unión de il-18 al il-18r. |
| BR112012021576A2 (pt) | 2010-02-26 | 2016-10-25 | Novo Nordisk As | composições estáveis contendo anticorpo. |
| RU2012153786A (ru) | 2010-05-28 | 2014-07-10 | Ново Нордиск А/С | Стабильные многодозовые композиции, содержащие антитело и консервант |
| SG10201505217WA (en) | 2010-07-09 | 2015-08-28 | Biogen Hemophilia Inc | Chimeric clotting factors |
| JP5813114B2 (ja) | 2010-08-25 | 2015-11-17 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | Ｉｌ−１８ｒ１に対する抗体およびその使用 |
| US9376489B2 (en) | 2012-09-07 | 2016-06-28 | Novartis Ag | IL-18 binding molecules |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1989004838A1 (en) | 1987-11-25 | 1989-06-01 | Immunex Corporation | Interleukin-1 receptors |
| EP0533006A1 (en) * | 1991-09-18 | 1993-03-24 | F.Hoffmann-La Roche & Co. Aktiengesellschaft | Chimaeric interleukin 5-receptor/immunoglobulin polypeptides |
| US5470952A (en) | 1993-10-20 | 1995-11-28 | Regeneron Pharmaceuticals, Inc. | CNTF and IL-6 antagonists |
| WO1996013593A2 (en) * | 1994-10-26 | 1996-05-09 | Procept, Inc. | Soluble single chain t cell receptors |
| US5853721A (en) | 1995-01-31 | 1998-12-29 | Hoffmann-La Roche Inc. | Antibody to interleukin-12 receptor |
| US5840530A (en) * | 1995-08-01 | 1998-11-24 | Hoffmann-La Roche Inc. | DNA encoding receptors for the beta-2 chain of human IL-12 |
| US5776731A (en) | 1996-02-21 | 1998-07-07 | Immunex Corporation | DNA encoding type-I interleukin-I receptor-like protein designated 2F1 |
| US7141393B2 (en) | 1996-12-26 | 2006-11-28 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Interleukin-18-receptor proteins |
| US6087116A (en) | 1997-03-12 | 2000-07-11 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Interleukin-18 (IL-18) receptor polypeptides and their uses |
| US6326472B1 (en) | 1997-10-15 | 2001-12-04 | Schering Corporation | Human receptor proteins; related reagents and methods |
| US6280955B1 (en) * | 1997-12-16 | 2001-08-28 | Tularik Inc. | Interleukin-1 receptor accessory proteins, nucleic acids and methods |
| US6472179B2 (en) | 1998-09-25 | 2002-10-29 | Regeneron Pharmaceuticals, Inc. | Receptor based antagonists and methods of making and using |
| US20020052475A1 (en) | 2000-07-20 | 2002-05-02 | Schering Ag | High affinity soluble interleukin-18 receptor |
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- 1999-01-22 PT PT99904222T patent/PT1047781E/pt unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| EP1047781A1 (en) | 2000-11-02 |
| PT1047781E (pt) | 2004-11-30 |
| NZ505880A (en) | 2003-06-30 |
| IL137178A (en) | 2007-06-17 |
| US20030199040A1 (en) | 2003-10-23 |
| CA2318482A1 (en) | 1999-07-29 |
| US20070135625A1 (en) | 2007-06-14 |
| US7169581B2 (en) | 2007-01-30 |
| US20100190211A1 (en) | 2010-07-29 |
| DK1047781T3 (da) | 2004-12-06 |
| ES2226335T3 (es) | 2005-03-16 |
| CA2318482C (en) | 2010-04-13 |
| DE69918946D1 (de) | 2004-09-02 |
| AU737592B2 (en) | 2001-08-23 |
| US6589764B1 (en) | 2003-07-08 |
| WO1999037772A1 (en) | 1999-07-29 |
| US7704945B2 (en) | 2010-04-27 |
| JP2002500886A (ja) | 2002-01-15 |
| AU2466899A (en) | 1999-08-09 |
| EP1047781B1 (en) | 2004-07-28 |
| DE69918946T2 (de) | 2005-07-28 |
| IL137178A0 (en) | 2001-07-24 |
| ATE272114T1 (de) | 2004-08-15 |
| US8053233B2 (en) | 2011-11-08 |
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