EA006767B1 - Применение ингибитора il-18 для приготовления лекарственного средства для лечения и/или профилактики заболевания сердца - Google Patents
Применение ингибитора il-18 для приготовления лекарственного средства для лечения и/или профилактики заболевания сердца Download PDFInfo
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- EA006767B1 EA006767B1 EA200300844A EA200300844A EA006767B1 EA 006767 B1 EA006767 B1 EA 006767B1 EA 200300844 A EA200300844 A EA 200300844A EA 200300844 A EA200300844 A EA 200300844A EA 006767 B1 EA006767 B1 EA 006767B1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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- C07K—PEPTIDES
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Landscapes
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01101959 | 2001-01-29 | ||
| PCT/EP2002/000844 WO2002060479A1 (en) | 2001-01-29 | 2002-01-28 | Use of il-18 inhibitors for the treatment and/or prevention of heart disease |
Publications (2)
| Publication Number | Publication Date |
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| EA200300844A1 EA200300844A1 (ru) | 2003-12-25 |
| EA006767B1 true EA006767B1 (ru) | 2006-04-28 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA200300844A EA006767B1 (ru) | 2001-01-29 | 2002-01-28 | Применение ингибитора il-18 для приготовления лекарственного средства для лечения и/или профилактики заболевания сердца |
| EA200501549A EA010180B1 (ru) | 2001-01-29 | 2002-01-28 | Применение ингибитора il-18 для приготовления лекарственного средства для лечения и/или профилактики кардиомиопатии |
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| Application Number | Title | Priority Date | Filing Date |
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| EA200501549A EA010180B1 (ru) | 2001-01-29 | 2002-01-28 | Применение ингибитора il-18 для приготовления лекарственного средства для лечения и/или профилактики кардиомиопатии |
Country Status (31)
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SK12942002A3 (sk) | 2000-02-10 | 2003-05-02 | Abbott Laboratories | Protilátky viažuce ľudský interleukín-18, spôsoby ich výroby a použitia |
| AU2002211744B8 (en) | 2000-10-11 | 2008-03-20 | 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 |
| AU2004238524B2 (en) | 2003-05-13 | 2011-06-23 | Merck Serono Sa | Active variants of the IL-18 binding protein and medical uses thereof |
| US7968684B2 (en) * | 2003-11-12 | 2011-06-28 | Abbott Laboratories | IL-18 binding proteins |
| JP4961559B2 (ja) * | 2004-03-11 | 2012-06-27 | 友昭 星野 | インターロイキン１８阻害剤を有効成分とする疾患の予防又は治療剤 |
| CA2609060C (en) | 2005-06-03 | 2014-07-15 | Urs Weber | Production of recombinant il-18 binding protein |
| PT1891088E (pt) | 2005-06-10 | 2011-12-19 | Ares Trading Sa | Processo para a purificação da proteína de ligação il-18 |
| TW200927060A (en) | 2007-11-05 | 2009-07-01 | Kci Licensing Inc | Identification of tissue for debridement |
| US9376489B2 (en) | 2012-09-07 | 2016-06-28 | Novartis Ag | IL-18 binding molecules |
| WO2015032932A1 (en) * | 2013-09-05 | 2015-03-12 | Ab2 Bio Sa | Il-18 binding protein (il-18bp) in inflammatory diseases |
| CN107660150B (zh) * | 2015-03-05 | 2023-10-24 | Ab2生物股份有限公司 | Il-18结合蛋白(il-18bp)和抗体在炎性疾病中 |
| US11091795B2 (en) | 2016-07-11 | 2021-08-17 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Compositions and methods for diagnosing and treating arrhythmias |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6204261B1 (en) * | 1995-12-20 | 2001-03-20 | Vertex Pharmaceuticals Incorporated | Inhibitors of interleukin-1β Converting enzyme inhibitors |
| US5605690A (en) * | 1989-09-05 | 1997-02-25 | Immunex Corporation | Methods of lowering active TNF-α levels in mammals using tumor necrosis factor receptor |
| NZ322197A (en) * | 1995-11-21 | 1999-02-25 | Yamanouchi Pharma Co Ltd | Pyrido[2,3-d] pyrimidine derivatives and pharmaceutical compositions thereof |
| ATE310528T1 (de) * | 1996-09-12 | 2005-12-15 | Idun Pharmaceuticals Inc | Hemmung der apoptose unter verwendung von inhibitoren der interleukin-1 beta converting enzym (ice)/ced-3 familie |
| JP4094066B2 (ja) * | 1996-12-06 | 2008-06-04 | バーテックス ファーマシューティカルズ インコーポレイテッド | インターロイキン−１β変換酵素のインヒビター |
| SK122199A3 (en) * | 1997-03-18 | 2000-12-11 | Basf Ag | Methods and compositions for modulating responsiveness to corticosteroids |
| IL121860A0 (en) * | 1997-08-14 | 1998-02-22 | Yeda Res & Dev | Interleukin-18 binding proteins their preparation and use |
| DE19743687C1 (de) * | 1997-10-06 | 1998-11-26 | Henkel Kgaa | Detergensgemische und deren Verwendung |
| AU4961499A (en) * | 1998-06-26 | 2000-01-17 | Eli Lilly And Company | 5-HT1f agonists |
| CA2340579A1 (en) * | 1998-09-01 | 2000-03-09 | Kabushiki Kaisha Hayashibara Seibutsu Kagaku Kenkyujo | Interleukin 18-binding protein |
| EP1022027A1 (en) * | 1999-01-22 | 2000-07-26 | Applied Research Systems ARS Holding N.V. | Tumor necrosis factor antagonists and their use in endometriosis |
| EP1165490B1 (en) * | 1999-03-16 | 2006-08-16 | Cytovia, Inc. | Substituted 2-aminobenzamide caspase inhibitors and the use thereof |
| CA2369619A1 (en) * | 1999-04-09 | 2000-10-19 | Cytovia, Inc. | Caspase inhibitors and the use thereof |
| AU6078500A (en) * | 1999-07-09 | 2001-01-30 | Amgen, Inc. | Combination therapy for conditions leading to bone loss |
| SK12942002A3 (sk) * | 2000-02-10 | 2003-05-02 | Abbott Laboratories | Protilátky viažuce ľudský interleukín-18, spôsoby ich výroby a použitia |
| CA2407895C (en) * | 2000-05-05 | 2012-12-18 | Applied Research Systems Ars Holding N.V. | Use of il-18 inhibitors for the treatment and/or prevention of atherosclerosis |
| WO2002032374A2 (en) * | 2000-10-18 | 2002-04-25 | Immunex Corporation | Methods for treating il-18 mediated disorders |
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