DE69918946T2 - Rezeptoren für il-18 - Google Patents
Rezeptoren für il-18 Download PDFInfo
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- DE69918946T2 DE69918946T2 DE69918946T DE69918946T DE69918946T2 DE 69918946 T2 DE69918946 T2 DE 69918946T2 DE 69918946 T DE69918946 T DE 69918946T DE 69918946 T DE69918946 T DE 69918946T DE 69918946 T2 DE69918946 T2 DE 69918946T2
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- polypeptide
- 1rrp1
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| US7883598P | 1998-03-20 | 1998-03-20 | |
| US78835P | 1998-03-20 | ||
| US9446998P | 1998-07-28 | 1998-07-28 | |
| US94469P | 1998-07-28 | ||
| PCT/US1999/001419 WO1999037772A1 (en) | 1998-01-23 | 1999-01-22 | Il-18 receptors |
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| DE69918946D1 DE69918946D1 (de) | 2004-09-02 |
| DE69918946T2 true DE69918946T2 (de) | 2005-07-28 |
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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 |
| US7122632B2 (en) | 1999-12-23 | 2006-10-17 | Zymogenetics, Inc. | Soluble Interleukin-20 receptor |
| CA2395539C (en) | 1999-12-23 | 2009-08-25 | Zymogenetics, Inc. | Soluble interleukin-20 receptor |
| US6610286B2 (en) | 1999-12-23 | 2003-08-26 | Zymogenetics, Inc. | Method for treating inflammation using soluble receptors to interleukin-20 |
| 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 |
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| WO2002012345A2 (en) | 2000-08-08 | 2002-02-14 | Zymogenetics, Inc. | Soluble zcytor 11 cytokine receptors |
| ES2267814T3 (es) | 2000-09-15 | 2007-03-16 | Zymogenetics, Inc. | Metodo para tratar la inflamacion. |
| AU1174402A (en) | 2000-10-11 | 2002-04-22 | 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 |
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| EP1293566A1 (en) * | 2001-09-17 | 2003-03-19 | Societe Des Produits Nestle S.A. | A soluble toll-like receptor |
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| US20040136992A1 (en) | 2002-08-28 | 2004-07-15 | Burton Paul B. J. | Compositions and method for treating cardiovascular disease |
| BR0315155A (pt) * | 2002-10-08 | 2005-08-16 | Ares Trading Sa | Uso de citocina capaz de ligar il-18bp e de inibir a atividade de uma segunda citocina |
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| TWI353991B (en) | 2003-05-06 | 2011-12-11 | Syntonix Pharmaceuticals Inc | Immunoglobulin chimeric monomer-dimer hybrids |
| US7968684B2 (en) * | 2003-11-12 | 2011-06-28 | Abbott Laboratories | IL-18 binding proteins |
| US20050100965A1 (en) | 2003-11-12 | 2005-05-12 | Tariq Ghayur | IL-18 binding proteins |
| JP4991307B2 (ja) | 2003-11-21 | 2012-08-01 | ザイモジェネティクス， インコーポレイテッド | 抗ｉｌ−２０抗体および結合パートナーならびに炎症において用いる方法 |
| 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 |
| US7537761B2 (en) | 2004-10-22 | 2009-05-26 | 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 |
| US20080292590A1 (en) * | 2006-02-22 | 2008-11-27 | Burkhard Becher | Soluble Receptors and Methods for Treating Autoimmune or Demyelinating Diseases |
| US7932055B2 (en) | 2006-06-22 | 2011-04-26 | Novo Nordisk A/S | Soluble heterodimeric CD94/NKG2 receptors fusion proteins |
| BRPI0811857A2 (pt) * | 2007-05-14 | 2014-10-21 | Biogen Idec Inc | Regiões fc (scfc) de cadeia simples, polipeptídeos de aglutinação que as compreendem e métodos relacionados. |
| 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. |
| WO2011104381A2 (en) | 2010-02-26 | 2011-09-01 | Novo Nordisk A/S | Stable antibody containing compositions |
| CA2800188A1 (en) | 2010-05-28 | 2011-12-01 | Novo Nordisk A/S | Stable multi-dose compositions comprising an antibody and a preservative |
| WO2012006635A1 (en) | 2010-07-09 | 2012-01-12 | Biogen Idec Hemophilia Inc. | Processable single chain molecules and polypeptides made using same |
| CA2805054A1 (en) | 2010-08-25 | 2012-03-01 | F. Hoffmann-La Roche Ag | Antibodies against il-18r1 and uses thereof |
| JOP20200308A1 (ar) | 2012-09-07 | 2017-06-16 | Novartis Ag | جزيئات إرتباط il-18 |
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 |
| EP1950226A3 (en) * | 1995-08-01 | 2010-08-11 | F. Hoffmann-La Roche AG | An antibody against a receptor for human interleukin - 12 and its use |
| 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 |
-
1999
- 1999-01-22 PT PT99904222T patent/PT1047781E/pt unknown
- 1999-01-22 IL IL13717899A patent/IL137178A0/xx active IP Right Grant
- 1999-01-22 DE DE69918946T patent/DE69918946T2/de not_active Expired - Lifetime
- 1999-01-22 AU AU24668/99A patent/AU737592B2/en not_active Ceased
- 1999-01-22 ES ES99904222T patent/ES2226335T3/es not_active Expired - Lifetime
- 1999-01-22 JP JP2000528679A patent/JP4271850B2/ja not_active Expired - Fee Related
- 1999-01-22 DK DK99904222T patent/DK1047781T3/da active
- 1999-01-22 EP EP99904222A patent/EP1047781B1/en not_active Expired - Lifetime
- 1999-01-22 AT AT99904222T patent/ATE272114T1/de active
- 1999-01-22 WO PCT/US1999/001419 patent/WO1999037772A1/en not_active Ceased
- 1999-01-22 NZ NZ505880A patent/NZ505880A/xx not_active IP Right Cessation
- 1999-01-22 CA CA2318482A patent/CA2318482C/en not_active Expired - Fee Related
-
2000
- 2000-07-05 IL IL137178A patent/IL137178A/en not_active IP Right Cessation
- 2000-07-21 US US09/621,502 patent/US6589764B1/en not_active Expired - Fee Related
-
2003
- 2003-05-15 US US10/439,458 patent/US7169581B2/en not_active Expired - Fee Related
-
2007
- 2007-01-29 US US11/699,676 patent/US7704945B2/en not_active Expired - Fee Related
-
2010
- 2010-03-03 US US12/716,993 patent/US8053233B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| IL137178A (en) | 2007-06-17 |
| US7169581B2 (en) | 2007-01-30 |
| AU2466899A (en) | 1999-08-09 |
| WO1999037772A1 (en) | 1999-07-29 |
| DE69918946D1 (de) | 2004-09-02 |
| CA2318482A1 (en) | 1999-07-29 |
| ATE272114T1 (de) | 2004-08-15 |
| JP2002500886A (ja) | 2002-01-15 |
| JP4271850B2 (ja) | 2009-06-03 |
| US7704945B2 (en) | 2010-04-27 |
| EP1047781A1 (en) | 2000-11-02 |
| US20070135625A1 (en) | 2007-06-14 |
| AU737592B2 (en) | 2001-08-23 |
| CA2318482C (en) | 2010-04-13 |
| NZ505880A (en) | 2003-06-30 |
| EP1047781B1 (en) | 2004-07-28 |
| ES2226335T3 (es) | 2005-03-16 |
| US20100190211A1 (en) | 2010-07-29 |
| US6589764B1 (en) | 2003-07-08 |
| US8053233B2 (en) | 2011-11-08 |
| DK1047781T3 (da) | 2004-12-06 |
| US20030199040A1 (en) | 2003-10-23 |
| IL137178A0 (en) | 2001-07-24 |
| PT1047781E (pt) | 2004-11-30 |
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