JP7609556B2 - 線維症の処置のためのインターフェロン－ラムダの医学的使用 - Google Patents
線維症の処置のためのインターフェロン－ラムダの医学的使用 Download PDFInfo
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Landscapes
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| JP2024125837A JP2024156844A (ja) | 2016-12-20 | 2024-08-01 | 線維症の処置のためのインターフェロン－ラムダの医学的使用 |
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| EP3375452B1 (en) * | 2017-03-16 | 2025-01-08 | Evangelos Andreakos | Use of lambda interferons in the treatment of an obesity-related disorder, atherosclerosis or a coagulation disorder |
| EP3849592A4 (en) * | 2018-08-23 | 2022-08-24 | Exalt Therapeutics, LLC | MODIFIED IFNL3 POLYPEPTIDES COMPRISING A PHARMACOKINETIC ENHANCING FRAGMENT AND THEIR USES |
| EP3999101A1 (en) * | 2019-07-18 | 2022-05-25 | ENYO Pharma | Method for decreasing adverse-effects of interferon |
| CN110882381B (zh) * | 2019-12-18 | 2020-11-17 | 中国人民解放军陆军军医大学第一附属医院 | 重组IFN-λ1蛋白在制备防治炎症性骨丢失药物中的应用 |
| WO2021119749A1 (en) * | 2019-12-20 | 2021-06-24 | The Council Of The Queensland Institute Of Medical Research | Treatment of gastrointestinal disease |
| CN114736878B (zh) * | 2021-01-07 | 2024-04-19 | 秦皇岛摩登狗生物科技有限公司 | 共表达猪干扰素l3和猪白介素22重组杆状病毒及应用 |
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| WO2011075605A2 (en) | 2009-12-18 | 2011-06-23 | Alios Biopharma, Inc. | Hyperglycosylated interferon variants and methods of use |
| JP2011522834A (ja) | 2008-06-05 | 2011-08-04 | ザイモジェネティクス リミテッド ライアビリティ カンパニー | Ｃ型肝炎の治療のためのペグ化ｉｉｉ型インターフェロンの使用 |
| JP2019505553A (ja) | 2016-02-19 | 2019-02-28 | アイガー・バイオファーマシューティカルズ・インコーポレイテッドＥｉｇｅｒ Ｂｉｏｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | インターフェロンラムダによるデルタ型肝炎ウイルス感染の処置 |
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| GB9113120D0 (en) | 1991-06-18 | 1991-08-07 | Kodak Ltd | Photographic processing apparatus |
| MXPA03009082A (es) | 2001-04-06 | 2004-11-22 | Maxygen Holdings Ltd | Variantes polipeptidicas de interferon gamma. |
| EP1551369A4 (en) | 2002-08-28 | 2007-05-09 | Intermune Inc | COMBINATION THERAPY FOR THE TREATMENT OF FIBROTIC DISEASES |
| AU2003225670A1 (en) | 2003-02-28 | 2004-09-28 | Intermune, Inc. | Interferon drug therapy for the treatment of viral diseases and liver fibrosis |
| AU2003299962A1 (en) | 2003-02-28 | 2004-09-28 | Intermune, Inc. | Interferon drug therapy for the treatment of viral diseases and liver fibrosis |
| WO2004105684A2 (en) | 2003-05-16 | 2004-12-09 | Intermune, Inc. | Combination therapy for proliferative disorders |
| GB0315457D0 (en) | 2003-07-01 | 2003-08-06 | Celltech R&D Ltd | Biological products |
| ES2551439T5 (es) | 2003-07-01 | 2018-11-08 | Ucb Biopharma Sprl | Fragmentos Fab de anticuerpos modificados |
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| US20070258946A1 (en) * | 2003-12-23 | 2007-11-08 | Blatt Lawrence M | Combination Therapy for Treating Hepatitis C Virus Infection |
| WO2005110478A2 (en) | 2004-04-13 | 2005-11-24 | Intermune, Inc. | Combination therapy for treating fibrotic disorders |
| GB0411186D0 (en) | 2004-05-19 | 2004-06-23 | Celltech R&D Ltd | Biological products |
| US7597884B2 (en) | 2004-08-09 | 2009-10-06 | Alios Biopharma, Inc. | Hyperglycosylated polypeptide variants and methods of use |
| EP1991679A2 (fr) | 2006-03-08 | 2008-11-19 | Biomethodes | Variants de l'interferon- gamma humain (ifngamma) |
| EP2535349A1 (en) | 2007-09-26 | 2012-12-19 | UCB Pharma S.A. | Dual specificity antibody fusions |
| US20110263484A1 (en) | 2008-10-13 | 2011-10-27 | Zymogenetics, Inc. | Single chain fc type iii interferons and methods of using same |
| WO2010048468A1 (en) | 2008-10-23 | 2010-04-29 | Concert Pharmaceuticals, Inc. | Deuterated macrocyclic inhibitors of viral ns3 protease |
| EP2350124A1 (en) * | 2008-11-20 | 2011-08-03 | Zymogenetics, Inc. | Il-29 mutants and uses thereof |
| IT1400236B1 (it) | 2010-05-10 | 2013-05-24 | Univ Bari | Impiego di composti noti per il trattamento dell'insufficienza renale cronica(irc) |
| CN102584979B (zh) * | 2011-01-18 | 2015-10-14 | 北京凯因科技股份有限公司 | PEG化干扰素λ |
| US9678074B2 (en) | 2012-03-28 | 2017-06-13 | The United States Of America, As Represented By The Secretary, Dept. Of Health And Human Services | Interferon-λ4 (IFNL4) protein, related nucleic acid molecules, and uses thereof |
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2022
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2011522834A (ja) | 2008-06-05 | 2011-08-04 | ザイモジェネティクス リミテッド ライアビリティ カンパニー | Ｃ型肝炎の治療のためのペグ化ｉｉｉ型インターフェロンの使用 |
| WO2011075605A2 (en) | 2009-12-18 | 2011-06-23 | Alios Biopharma, Inc. | Hyperglycosylated interferon variants and methods of use |
| JP2019505553A (ja) | 2016-02-19 | 2019-02-28 | アイガー・バイオファーマシューティカルズ・インコーポレイテッドＥｉｇｅｒ Ｂｉｏｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | インターフェロンラムダによるデルタ型肝炎ウイルス感染の処置 |
Non-Patent Citations (5)
| Title |
|---|
| Ａｍ． Ｊ． Ｒｅｓｐｉｒ． Ｃｅｌｌ Ｍｏｌ． Ｂｉｏｌ．， ２００５， Ｖｏｌ．３２， ｐｐ．９３－９８ |
| Ｈｅｐａｔｏｌｏｇｙ， ２００７， Ｖｏｌ．４６， Ｎｏ．２， ｐｐ．３８８－３９４ |
| Ｎａｔｕｒｅ Ｉｍｍｕｎｏｌｏｇｙ， ２０１５， Ｖｏｌ．１６， ｐｐ．８０２－８０９ |
| Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， ２０１０， Ｖｏｌ．３， ｐｐ．１１６２－１１８６ |
| ＰＬｏＳ Ｐａｔｈｏｇｅｎｓ， ２００８， Ｖｏｌ．４， Ｎｏ．３， ＃ｅ１００００１７ |
Also Published As
| Publication number | Publication date |
|---|---|
| GB201621728D0 (en) | 2017-02-01 |
| JP2024156844A (ja) | 2024-11-06 |
| WO2018115199A1 (en) | 2018-06-28 |
| EP3558342B1 (en) | 2025-01-29 |
| US20190374610A1 (en) | 2019-12-12 |
| BR112019012084A2 (pt) | 2019-11-12 |
| US11975046B2 (en) | 2024-05-07 |
| UY37534A (es) | 2018-09-28 |
| EA201991175A1 (ru) | 2019-11-29 |
| TW201828973A (zh) | 2018-08-16 |
| EP3558342A1 (en) | 2019-10-30 |
| JP2022081677A (ja) | 2022-05-31 |
| CA3044949A1 (en) | 2018-06-28 |
| US20240000893A1 (en) | 2024-01-04 |
| AR110404A1 (es) | 2019-03-27 |
| CN110381985A (zh) | 2019-10-25 |
| JP2020511415A (ja) | 2020-04-16 |
| ES3019566T3 (en) | 2025-05-20 |
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