JP2011522834A - 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 - Google Patents
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 Download PDFInfo
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| US16776309P | 2009-04-08 | 2009-04-08 | |
| US61/167,763 | 2009-04-08 | ||
| PCT/US2009/046451 WO2009149377A1 (en) | 2008-06-05 | 2009-06-05 | Use of pegylated type iii interferons for the treatment of hepatitis c |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020511415A (ja) * | 2016-12-20 | 2020-04-16 | ユーシービー バイオファルマ エスアールエル | 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 |
| JP2022548652A (ja) * | 2019-09-20 | 2022-11-21 | エフ．ホフマン－ラ ロシュ アーゲー | コアタンパク質アロステリックモジュレータを使用してｈｂｖ感染を処置する方法 |
| JP2023120389A (ja) * | 2019-03-05 | 2023-08-29 | プロージット ソウル バイオテクノロジー （ベイジン） カンパニー リミテッド | 融合ポリペプチドおよび使用方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| ES2286128T3 (es) | 2000-06-30 | 2007-12-01 | Zymogenetics, Inc. | Proteina zcyto21 tipo interferon. |
| US7910313B2 (en) | 2001-04-20 | 2011-03-22 | Zymogenetics, Inc. | Cytokine protein family |
| JP4808157B2 (ja) | 2003-08-07 | 2011-11-02 | 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 | Ｉｌ−２８およびｉｌ−２９の均一な調製物 |
| AU2005231476B2 (en) | 2004-04-02 | 2011-09-01 | Zymogenetics, Inc. | Il-28 and il-29 cysteine mutants for treating viral infection |
| UY32099A (es) | 2008-09-11 | 2010-04-30 | Enanta Pharm Inc | Inhibidores macrocíclicos de serina proteasas de hepatitis c |
| WO2011098644A2 (es) | 2010-02-09 | 2011-08-18 | Proyecto De Biomedicina Cima, S.L. | Composiciones para el tratamiento de enfermedades infecciosas y tumorales |
| WO2012031763A1 (en) * | 2010-09-08 | 2012-03-15 | Twincore Zentrum Fuer Experimentelle Und Klinische Infektionsforschung Gmbh | Use of inhibitors of phospholipase a2 for the treatment or prevention of flavivirus infection |
| AU2011305652B2 (en) | 2010-09-22 | 2016-10-20 | Janssen Biopharma, Inc. | Azido nucleosides and nucleotide analogs |
| CN103534256B (zh) | 2010-12-30 | 2016-08-10 | 益安药业 | 大环丙型肝炎丝氨酸蛋白酶抑制剂 |
| KR20140003521A (ko) | 2010-12-30 | 2014-01-09 | 이난타 파마슈티칼스, 인코포레이티드 | 페난트리딘 매크로사이클릭 ｃ형 간염 세린 프로테아제 억제제 |
| 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 |
| US10201584B1 (en) | 2011-05-17 | 2019-02-12 | Abbvie Inc. | Compositions and methods for treating HCV |
| WO2013029062A1 (en) * | 2011-08-25 | 2013-02-28 | Nanogen Pharmaceutical Biotechnology Co., Ltd | Peginterferon lambda 1 conjugates, processes for their preparation, pharmaceutical compositions containing these conjugates and processes for making the same |
| EP2748328A4 (en) * | 2011-08-25 | 2015-03-04 | Nanogen Pharmaceutical Biotechnology | PEG-INTERFERON LAMBDA 1 CONJUGATES |
| US8492386B2 (en) | 2011-10-21 | 2013-07-23 | Abbvie Inc. | Methods for treating HCV |
| DE112012003510T5 (de) | 2011-10-21 | 2015-03-19 | Abbvie Inc. | Verfahren zur Behandlung von HCV umfassend mindestens zwei direkt wirkende antivirale Wirkstoffe, Ribavirin aber nicht Interferon |
| US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
| CN104023726A (zh) | 2011-10-21 | 2014-09-03 | 艾伯维公司 | 用于治疗hcv的一种或多种daa的联合治疗(例如，与abt-072或abt-333) |
| CN102533840A (zh) * | 2011-12-13 | 2012-07-04 | 江南大学 | 毕赤酵母制备人白细胞介素29成熟肽的方法 |
| US8454947B1 (en) | 2012-03-01 | 2013-06-04 | Nanogen Pharmaceutical Biotechnology | PEG-interferon lambda 1 conjugates |
| CN104045704B (zh) * | 2013-03-11 | 2016-08-10 | 中国医学科学院基础医学研究所 | PEG化重组人IFN-λ1、其制备方法和用途 |
| WO2015103490A1 (en) | 2014-01-03 | 2015-07-09 | Abbvie, Inc. | Solid antiviral dosage forms |
| CN109293782A (zh) * | 2014-01-08 | 2019-02-01 | 德益阳光生物技术（北京）有限责任公司 | 融合多肽及使用方法 |
| WO2015136455A1 (en) * | 2014-03-13 | 2015-09-17 | Novartis Ag | New treatments of hepatitis c virus infection |
| MX2016014731A (es) * | 2014-05-12 | 2017-05-04 | Conatus Pharmaceuticals Inc | Tratamiento de las complicaciones de la enfermedad cronica del higado con enfermedades de caspasa. |
| US11759500B2 (en) * | 2014-07-24 | 2023-09-19 | Abion Inc. | PEGylated interferon-beta variant |
| JP7129703B2 (ja) | 2016-04-28 | 2022-09-02 | エモリー ユニバーシティー | アルキン含有ヌクレオチド及びヌクレオシド治療組成物並びにそれらに関連した使用 |
| RU2678332C1 (ru) | 2017-09-08 | 2019-01-28 | Общество с ограниченной ответственностью "Саентифик Фьючер Менеджмент" (ООО "СФМ") | Пегилированный интерферон лямбда, обладающий высокой биодоступностью при пероральном применении, и способ его получения |
| AU2020249331B2 (en) | 2019-03-25 | 2026-02-05 | F. Hoffmann-La Roche Ag | Solid forms of a compound of HBV core protein allosteric modifier |
| WO2021119749A1 (en) * | 2019-12-20 | 2021-06-24 | The Council Of The Queensland Institute Of Medical Research | Treatment of gastrointestinal disease |
| CN115968291A (zh) * | 2020-04-22 | 2023-04-14 | 南湖制药公司 | 聚乙二醇化干扰素tau及其组合物和方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007012033A2 (en) * | 2005-07-20 | 2007-01-25 | Zymogenetics, Inc. | Il28 and il29 truncated cysteine mutants and antiviral methods of using same |
| JP2007531741A (ja) * | 2004-04-02 | 2007-11-08 | ザイモジェネティクス， インコーポレイテッド | Ｉｌ−２８およびｉｌ−２９システイン変異体を用いるウイルス感染を治療するための方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2286128T3 (es) * | 2000-06-30 | 2007-12-01 | Zymogenetics, Inc. | Proteina zcyto21 tipo interferon. |
| US7038032B2 (en) * | 2001-04-20 | 2006-05-02 | Zymogenetics, Inc. | Cytokine protein family |
| PT3025726T (pt) * | 2002-01-18 | 2020-01-09 | Biogen Ma Inc | Compostos do polímero polialquileno e utilizações dos mesmos |
| CA2503305A1 (en) * | 2002-10-23 | 2004-05-06 | Zymogenetics, Inc. | Methods for treating viral infection using il-28 and il-29 |
| JP4808157B2 (ja) * | 2003-08-07 | 2011-11-02 | 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 | Ｉｌ−２８およびｉｌ−２９の均一な調製物 |
| US7351689B2 (en) * | 2004-07-29 | 2008-04-01 | Zymogenetics, Inc. | Use of IL-28 and IL-29 to treat cancer and autoimmune disorders |
| US20070004635A1 (en) * | 2005-06-02 | 2007-01-04 | Schering Corporation | Method of treating interferon non-responders using HCV protease inhibitor |
| EP1909821A2 (en) * | 2005-07-20 | 2008-04-16 | ZymoGenetics, Inc. | Use of truncated cysteine il28 and il29 mutants to treat cancers and autoimmune disorders |
| JP5364375B2 (ja) * | 2005-10-04 | 2013-12-11 | 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 | Ｉｌ−２９の生産および精製の方法 |
-
2009
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- 2009-06-05 AU AU2009255994A patent/AU2009255994B2/en not_active Expired - Fee Related
- 2009-06-05 EP EP09759535A patent/EP2296691A1/en not_active Withdrawn
- 2009-06-05 CN CN2009801261152A patent/CN102099051A/zh active Pending
- 2009-06-05 JP JP2011512703A patent/JP2011522834A/ja active Pending
- 2009-06-05 CN CN201310408018.0A patent/CN103536906A/zh active Pending
- 2009-06-05 WO PCT/US2009/046451 patent/WO2009149377A1/en not_active Ceased
- 2009-06-05 US US12/996,358 patent/US20110165121A1/en not_active Abandoned
- 2009-06-05 CA CA2727026A patent/CA2727026A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007531741A (ja) * | 2004-04-02 | 2007-11-08 | ザイモジェネティクス， インコーポレイテッド | Ｉｌ−２８およびｉｌ−２９システイン変異体を用いるウイルス感染を治療するための方法 |
| WO2007012033A2 (en) * | 2005-07-20 | 2007-01-25 | Zymogenetics, Inc. | Il28 and il29 truncated cysteine mutants and antiviral methods of using same |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2020511415A (ja) * | 2016-12-20 | 2020-04-16 | ユーシービー バイオファルマ エスアールエル | 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 |
| JP2022081677A (ja) * | 2016-12-20 | 2022-05-31 | ユーシービー バイオファルマ エスアールエル | 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 |
| US11975046B2 (en) | 2016-12-20 | 2024-05-07 | UCB Biopharma SRL | Medical use of interferon-lambda for the treatment of fibrosis |
| JP7609556B2 (ja) | 2016-12-20 | 2025-01-07 | ユーシービー バイオファルマ エスアールエル | 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 |
| JP2023120389A (ja) * | 2019-03-05 | 2023-08-29 | プロージット ソウル バイオテクノロジー （ベイジン） カンパニー リミテッド | 融合ポリペプチドおよび使用方法 |
| JP7712982B2 (ja) | 2019-03-05 | 2025-07-24 | プロージット ソウル バイオテクノロジー （ベイジン） カンパニー リミテッド | 融合ポリペプチドおよび使用方法 |
| JP2022548652A (ja) * | 2019-09-20 | 2022-11-21 | エフ．ホフマン－ラ ロシュ アーゲー | コアタンパク質アロステリックモジュレータを使用してｈｂｖ感染を処置する方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| RU2496514C2 (ru) | 2013-10-27 |
| RU2010154092A (ru) | 2012-07-20 |
| WO2009149377A1 (en) | 2009-12-10 |
| US20110165121A1 (en) | 2011-07-07 |
| AU2009255994B2 (en) | 2014-07-17 |
| AU2009255994A1 (en) | 2009-12-10 |
| AU2009255994A2 (en) | 2011-02-17 |
| EP2296691A1 (en) | 2011-03-23 |
| CA2727026A1 (en) | 2009-12-10 |
| CN103536906A (zh) | 2014-01-29 |
| CN102099051A (zh) | 2011-06-15 |
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