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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| US6472179B2 (en) * | 1998-09-25 | 2002-10-29 | Regeneron Pharmaceuticals, Inc. | Receptor based antagonists and methods of making and using |
| 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 |
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| CA2399148A1 (en) | 2000-02-10 | 2001-08-16 | Abbott Laboratories | Antibodies that bind human interleukin-18 and methods of making and using |
| 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 |
| DE60123998T2 (de) | 2000-08-08 | 2007-09-06 | Zymogenetics, Inc., Seattle | Lösliche zcyctor 11 cytokinrezeptoren |
| ATE333888T1 (de) | 2000-09-15 | 2006-08-15 | Zymogenetics Inc | Verwendung eines polypeptids, welches die extrazelluläre domäne von il-20ra und il-20rb enthält, zur behandlung von entzündungen |
| JP2004528010A (ja) * | 2000-10-11 | 2004-09-16 | バイロン・セラピューティックス・インコーポレーテッド | 免疫モジュレーションのための核酸およびポリペプチド |
| 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 |
| EP2295081B1 (en) | 2001-06-26 | 2018-10-31 | 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 |
| JP2006508056A (ja) | 2002-08-28 | 2006-03-09 | イミュネックス・コーポレーション | 心臓血管疾患を治療するための組成物および方法 |
| AU2003299919B2 (en) * | 2002-10-08 | 2009-08-06 | Ares Trading S.A. | The use of cytokine able to bind IL-18BP and of inhibiting the activity of a second cytokine |
| JP2007525438A (ja) | 2003-03-24 | 2007-09-06 | 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 |
| 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 |
| WO2005052001A2 (en) | 2003-11-21 | 2005-06-09 | Zymogenetics, Inc. | Anti-il-20 receptor antibodies and binding partners and methods of using in inflammation |
| 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 |
| AU2005299809B2 (en) | 2004-10-22 | 2010-12-02 | Zymogenetics, Inc. | Anti-IL-22RA antibodies and binding partners and methods of using in inflammation |
| CN101146823A (zh) * | 2005-02-15 | 2008-03-19 | 阿波罗生命科学有限公司 | 分子及其嵌合分子 |
| WO2007096398A1 (en) * | 2006-02-22 | 2007-08-30 | University Of Zurich | Soluble receptors and methods for treating autoimmune or demyelinating diseases |
| EP2035452B1 (en) | 2006-06-22 | 2012-04-25 | Novo Nordisk A/S | Soluble heterodimeric receptors and uses thereof |
| EP2158318A2 (en) * | 2007-05-14 | 2010-03-03 | Biogen Idec MA, Inc. | Single-chain fc (scfc) regions, binding polypeptides comprising same, and methods related thereto |
| 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. |
| EP3409289B1 (en) | 2010-02-26 | 2020-09-30 | Novo Nordisk A/S | Stable antibody containing compositions |
| RU2012153786A (ru) | 2010-05-28 | 2014-07-10 | Ново Нордиск А/С | Стабильные многодозовые композиции, содержащие антитело и консервант |
| TW201217527A (en) * | 2010-07-09 | 2012-05-01 | Biogen Idec Hemophilia Inc | Processable single chain molecules and polypeptides made using same |
| KR101603001B1 (ko) | 2010-08-25 | 2016-03-11 | 에프. 호프만-라 로슈 아게 | Il-18r1에 대한 항체 및 그의 용도 |
| 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 |
| EP0759466B1 (en) * | 1995-08-01 | 2005-12-28 | F. Hoffmann-La Roche Ag | Low binding affinity interleukin-12 beta receptors |
| 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
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- 1999-01-22 AU AU24668/99A patent/AU737592B2/en not_active Ceased
- 1999-01-22 DE DE69918946T patent/DE69918946T2/de not_active Expired - Lifetime
- 1999-01-22 WO PCT/US1999/001419 patent/WO1999037772A1/en not_active Ceased
- 1999-01-22 AT AT99904222T patent/ATE272114T1/de active
- 1999-01-22 DK DK99904222T patent/DK1047781T3/da active
- 1999-01-22 NZ NZ505880A patent/NZ505880A/xx not_active IP Right Cessation
- 1999-01-22 PT PT99904222T patent/PT1047781E/pt unknown
- 1999-01-22 IL IL13717899A patent/IL137178A0/xx active IP Right Grant
- 1999-01-22 ES ES99904222T patent/ES2226335T3/es not_active Expired - Lifetime
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| Publication number | Publication date |
|---|---|
| PT1047781E (pt) | 2004-11-30 |
| US7169581B2 (en) | 2007-01-30 |
| IL137178A0 (en) | 2001-07-24 |
| US20070135625A1 (en) | 2007-06-14 |
| US7704945B2 (en) | 2010-04-27 |
| DE69918946T2 (de) | 2005-07-28 |
| DK1047781T3 (da) | 2004-12-06 |
| CA2318482C (en) | 2010-04-13 |
| ES2226335T3 (es) | 2005-03-16 |
| US8053233B2 (en) | 2011-11-08 |
| DE69918946D1 (de) | 2004-09-02 |
| EP1047781B1 (en) | 2004-07-28 |
| US6589764B1 (en) | 2003-07-08 |
| ATE272114T1 (de) | 2004-08-15 |
| US20030199040A1 (en) | 2003-10-23 |
| IL137178A (en) | 2007-06-17 |
| CA2318482A1 (en) | 1999-07-29 |
| WO1999037772A1 (en) | 1999-07-29 |
| JP2002500886A (ja) | 2002-01-15 |
| AU737592B2 (en) | 2001-08-23 |
| EP1047781A1 (en) | 2000-11-02 |
| NZ505880A (en) | 2003-06-30 |
| US20100190211A1 (en) | 2010-07-29 |
| AU2466899A (en) | 1999-08-09 |
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