JP2012519181A - ヌクレオシドポリメラーゼインヒビターと大環状プロテアーゼインヒビターの併用ならびにｃ型肝炎、肝臓線維症および肝臓機能障害の治療におけるその使用 - Google Patents
ヌクレオシドポリメラーゼインヒビターと大環状プロテアーゼインヒビターの併用ならびにｃ型肝炎、肝臓線維症および肝臓機能障害の治療におけるその使用 Download PDFInfo
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- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
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- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
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Landscapes
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| US61/257,367 | 2009-11-02 | ||
| PCT/US2010/025611 WO2010099458A1 (en) | 2009-02-27 | 2010-02-26 | Combination of a nucleoside polymerase inhibitor with a macrocyclic protease inhibitor and use thereof in the treatment of hepatitis c, liver fibrosis and impaired liver function |
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Cited By (1)
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| JP2015528511A (ja) * | 2012-09-18 | 2015-09-28 | アッヴィ・インコーポレイテッド | Ｃ型肝炎を治療するための方法 |
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| EP4032897B1 (en) | 2003-05-30 | 2025-01-29 | Gilead Pharmasset LLC | Modified fluorinated nucleoside analogues |
| US7491794B2 (en) * | 2003-10-14 | 2009-02-17 | Intermune, Inc. | Macrocyclic compounds as inhibitors of viral replication |
| GEP20105124B (en) | 2005-07-25 | 2010-11-25 | Array Biopharma Inc | Novel macrocyclic inhibitors of hepatitis c virus replication |
| UA93990C2 (ru) * | 2005-10-11 | 2011-03-25 | Интермюн, Инк. | Соединения и способ ингибирования репликации вируса гепатита c |
| MX2007009796A (es) | 2007-08-14 | 2009-02-25 | Cell Therapy And Technology S | Gel conteniendo pirfenidona. |
| KR20110005869A (ko) | 2008-04-15 | 2011-01-19 | 인터뮨, 인크. | Ｃ형 간염 바이러스 복제의 신규한 마크로사이클릭 억제제 |
| AR075584A1 (es) | 2009-02-27 | 2011-04-20 | Intermune Inc | COMPOSICIONES TERAPEUTICAS QUE COMPRENDEN beta-D-2'-DESOXI-2'-FLUORO-2'-C-METILCITIDINA Y UN DERIVADO DE ACIDO ISOINDOL CARBOXILICO Y SUS USOS. COMPUESTO. |
| HRP20130862T1 (hr) | 2009-09-21 | 2013-10-25 | Gilead Sciences, Inc. | Procesi i intermedijeri za pripravu analoga 1'-cijanokarbanukleozida |
| NZ606141A (en) | 2010-07-19 | 2015-03-27 | Gilead Sciences Inc | Methods for the preparation of diasteromerically pure phosphoramidate prodrugs |
| UA111163C2 (uk) | 2010-07-22 | 2016-04-11 | Гайлід Сайєнсіз, Інк. | Способи й сполуки для лікування вірусних інфекцій paramyxoviridae |
| TW201300106A (zh) * | 2010-11-09 | 2013-01-01 | Hoffmann La Roche | 治療ｈｃｖ感染之醫藥組合物 |
| MX2011007675A (es) | 2011-07-19 | 2012-07-11 | Cell Therapy And Technology S A De C V | Procedimiento para la fabricacion de una composicion farmaceutica en forma de tabletas de liberacion prolongada conteniendo pirfenidona y su aplicacion en la regresion de la insuficiencia renal cronica, contractura capsular mamaria y fibrosis hepatica humanas. |
| GB2515942A (en) | 2011-10-21 | 2015-01-07 | Abbvie Inc | Combination treatment (e.g. with ABT-072 or ABT-333) of DAAs for use in treating HCV |
| US8492386B2 (en) | 2011-10-21 | 2013-07-23 | Abbvie Inc. | Methods for treating HCV |
| US8466159B2 (en) | 2011-10-21 | 2013-06-18 | Abbvie Inc. | Methods for treating HCV |
| PT107894A (pt) | 2011-10-21 | 2014-10-31 | Abbvie Inc | Métodos para o tratamento de hcv compreendendo pelo menos dois agentes antivirais de actuação directa, ribavirina, mas não interferão. |
| EP2802595B1 (en) | 2012-01-11 | 2016-01-06 | AbbVie Inc. | Processes for making hcv protease inhibitors |
| MX346763B (es) | 2012-03-28 | 2017-03-31 | Cell Therapy And Tech S A De C V | Composición tópica semisólida conteniendo pirfenidona y dialil óxido de disulfuro modificado (odd-m) para eliminar o prevenir el acné. |
| EA201590006A1 (ru) * | 2012-06-12 | 2015-05-29 | Ф. Хоффманн-Ля Рош Аг | Комбинация терапевтических средств для лечения инфекции, вызванной вирусом гепатита c |
| MX356551B (es) | 2012-08-23 | 2018-06-04 | Grupo Medifarma S A De C V Star | Composición antiséptica, antiseborreica y exfoliante para eliminar o prevenir el acné. |
| TWI767201B (zh) | 2014-10-29 | 2022-06-11 | 美商基利科學股份有限公司 | 絲狀病毒科病毒感染之治療 |
| MY190867A (en) | 2015-03-06 | 2022-05-13 | Atea Pharmaceuticals Inc | ? -d-2'-deoxy-2'-?-fluoro-2'- ? -c-substituted-2-modified-n6-substituted purine nucleotides for hcv treatment |
| MA52371A (fr) | 2015-09-16 | 2021-09-22 | Gilead Sciences Inc | Méthodes de traitement d'infections dues aux coronaviridae |
| US11192914B2 (en) | 2016-04-28 | 2021-12-07 | Emory University | Alkyne containing nucleotide and nucleoside therapeutic compositions and uses related thereto |
| US10711029B2 (en) | 2016-07-14 | 2020-07-14 | Atea Pharmaceuticals, Inc. | Beta-d-2′-deoxy-2′-alpha-fluoro-2′-beta-c-substituted-4′fluoro-n6-substituted-6-amino-2-substituted purine nucleotides for the treatment of hepatitis c virus infection |
| PL3512863T3 (pl) | 2016-09-07 | 2022-04-04 | Atea Pharmaceuticals, Inc. | 2'-Podstawione-N6-podstawione nukleotydy purynowe do leczenia zakażeń wirusem RNA |
| CN106674224A (zh) * | 2016-12-20 | 2017-05-17 | 天津迈德新医药科技有限公司 | mPEG4‑阿巴卡韦及其制备方法和应用 |
| IL295609B2 (en) | 2017-02-01 | 2023-11-01 | Atea Pharmaceuticals Inc | Nucleotide hemisulfate salt for the treatment of hepatitis C virus |
| CA3056072C (en) | 2017-03-14 | 2022-08-23 | Gilead Sciences, Inc. | Methods of treating feline coronavirus infections |
| JP2020518578A (ja) | 2017-05-01 | 2020-06-25 | ギリアード サイエンシーズ， インコーポレイテッド | （Ｓ）−２−エチルブチル２−（（（Ｓ）−（（（２Ｒ，３Ｓ，４Ｒ，５Ｒ）−５−（４−アミノピロロ［２，１−ｆ］［１，２，４］トリアジン−７−イル）−５−シアノ−３，４−ジヒドロキシテトラヒドロフラン−２−イル）メトキシ）（フェノキシ）ホスホリル）アミノ）プロパノエートの結晶形態 |
| ES3000461T3 (en) | 2017-07-11 | 2025-02-28 | Gilead Sciences Inc | Compositions comprising an rna polymerase inhibitor and cyclodextrin for treating viral infections |
| CN112351799A (zh) | 2018-04-10 | 2021-02-09 | 阿堤亚制药公司 | 具有硬化的hcv感染患者的治疗 |
| JP2023512656A (ja) | 2020-01-27 | 2023-03-28 | ギリアード サイエンシーズ， インコーポレイテッド | ＳＡＲＳ ＣｏＶ－２感染を治療するための方法 |
| US10874687B1 (en) | 2020-02-27 | 2020-12-29 | Atea Pharmaceuticals, Inc. | Highly active compounds against COVID-19 |
| TWI890963B (zh) | 2020-03-12 | 2025-07-21 | 美商基利科學股份有限公司 | 1'-氰基核苷之製備方法 |
| AU2021251689B2 (en) | 2020-04-06 | 2024-06-13 | Gilead Sciences, Inc. | Inhalation formulations of 1'-cyano substituted carbanucleoside analogs |
| TW202532084A (zh) | 2020-05-29 | 2025-08-16 | 美商基利科學股份有限公司 | 瑞德西韋之治療方法 |
| IL299202A (en) | 2020-06-24 | 2023-02-01 | Gilead Sciences Inc | 1'-cyano nucleoside analogs and uses thereof |
| PE20231983A1 (es) | 2020-08-27 | 2023-12-12 | Gilead Sciences Inc | Compuestos y metodos para el tratamiento de infecciones virales |
| BR112023026356A2 (pt) | 2021-06-17 | 2024-03-05 | Atea Pharmaceuticals Inc | Método para tratar vírus da hepatite c ou uma condição resultante de uma infecção por hepatite c, combinação, uso da combinação, composição farmacêutica, e, kit para o tratamento de vírus da hepatite c |
| CA3244278A1 (en) | 2022-03-02 | 2023-09-07 | Gilead Sciences Inc | COMPOUNDS AND METHODS FOR THE TREATMENT OF VIRAL INFECTIONS |
| US12357577B1 (en) | 2024-02-02 | 2025-07-15 | Gilead Sciences, Inc. | Pharmaceutical formulations and uses thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008506648A (ja) * | 2004-07-14 | 2008-03-06 | ノバルティス アクチエンゲゼルシャフト | Ｃ型肝炎（ｈｃｖ）処置のためのシクロスポリンとペグ化インターフェロンの組合せ剤の使用 |
| WO2008144072A1 (en) * | 2007-05-21 | 2008-11-27 | Vertex Pharmaceuticals Incorporated | Dose forms comprising vx- 950 and their dosage regimen |
| JP2009502920A (ja) * | 2005-07-25 | 2009-01-29 | インターミューン・インコーポレーテッド | Ｃ型肝炎ウイルス複製の新規大環状阻害剤 |
Family Cites Families (193)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3547119A (en) | 1967-12-08 | 1970-12-15 | Baxter Laboratories Inc | Catheter assembly |
| US4311137A (en) | 1980-04-30 | 1982-01-19 | Sherwood Medical Industries Inc. | Infusion device |
| US4531937A (en) | 1983-01-24 | 1985-07-30 | Pacesetter Systems, Inc. | Introducer catheter apparatus and method of use |
| HU196607B (en) | 1985-05-15 | 1988-12-28 | Wellcome Found | Process for producing dideoxy-nucleosides and pharmaceutics comprising such compounds |
| US4755173A (en) | 1986-02-25 | 1988-07-05 | Pacesetter Infusion, Ltd. | Soft cannula subcutaneous injection set |
| US5149820A (en) | 1987-03-11 | 1992-09-22 | Norsk Hydro A.S. | Deuterated compounds |
| GB8815265D0 (en) * | 1988-06-27 | 1988-08-03 | Wellcome Found | Therapeutic nucleosides |
| US5232928A (en) | 1989-07-25 | 1993-08-03 | Boehringer Ingelheim Pharmaceuticals, Inc. | Tetrahydroisoquinoline amides |
| US5545143A (en) | 1993-01-21 | 1996-08-13 | T. S. I. Medical | Device for subcutaneous medication delivery |
| US5624949A (en) * | 1993-12-07 | 1997-04-29 | Eli Lilly And Company | Protein kinase C inhibitors |
| US6334997B1 (en) | 1994-03-25 | 2002-01-01 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
| US6693072B2 (en) * | 1994-06-02 | 2004-02-17 | Aventis Pharmaceuticals Inc. | Elastase inhibitors |
| US5847135A (en) | 1994-06-17 | 1998-12-08 | Vertex Pharmaceuticals, Incorporated | Inhibitors of interleukin-1β converting enzyme |
| US5756466A (en) | 1994-06-17 | 1998-05-26 | Vertex Pharmaceuticals, Inc. | Inhibitors of interleukin-1β converting enzyme |
| US5968895A (en) | 1996-12-11 | 1999-10-19 | Praecis Pharmaceuticals, Inc. | Pharmaceutical formulations for sustained drug delivery |
| US6767991B1 (en) * | 1997-08-11 | 2004-07-27 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis C inhibitor peptides |
| US6323180B1 (en) * | 1998-08-10 | 2001-11-27 | Boehringer Ingelheim (Canada) Ltd | Hepatitis C inhibitor tri-peptides |
| US7157430B2 (en) | 1998-10-22 | 2007-01-02 | Idun Pharmaceuticals, Inc. | (Substituted)acyl dipeptidyl inhibitors of the ICE/CED-3 family of cysteine proteases |
| US6376531B1 (en) * | 1998-11-13 | 2002-04-23 | Rupert Charles Bell | Method of treatment using deuterium compounds |
| UA74546C2 (en) | 1999-04-06 | 2006-01-16 | Boehringer Ingelheim Ca Ltd | Macrocyclic peptides having activity relative to hepatitis c virus, a pharmaceutical composition and use of the pharmaceutical composition |
| US6608027B1 (en) * | 1999-04-06 | 2003-08-19 | Boehringer Ingelheim (Canada) Ltd | Macrocyclic peptides active against the hepatitis C virus |
| US7256005B2 (en) | 1999-08-10 | 2007-08-14 | The Chancellor, Masters And Scholars Of The University Of Oxford | Methods for identifying iminosugar derivatives that inhibit HCV p7 ion channel activity |
| ATE297946T1 (de) | 2000-04-03 | 2005-07-15 | Vertex Pharma | Inhibitoren von serin proteasen, speziell der hepatitis-c-virus ns3-protease |
| ES2317900T3 (es) * | 2000-04-05 | 2009-05-01 | Schering Corporation | Inhibidores de serina proteasa ns3 macrociclicos del virus de la hepatitis c que comprenden fragmentos n-ciclicas p2. |
| PL358591A1 (en) * | 2000-04-19 | 2004-08-09 | Schering Corporation | Macrocyclic ns3-serine protease inhibitors of hepatitis c virus comprising alkyl and aryl alanine p2 moieties |
| US7244721B2 (en) * | 2000-07-21 | 2007-07-17 | Schering Corporation | Peptides as NS3-serine protease inhibitors of hepatitis C virus |
| CN1498224A (zh) * | 2000-07-21 | 2004-05-19 | ���鹫˾ | 用作丙型肝炎病毒ns3-丝氨酸蛋白酶抑制剂的新型肽 |
| HUP0500456A3 (en) | 2000-11-20 | 2012-05-02 | Bristol Myers Squibb Co | Hepatitis c tripeptide inhibitors, pharmaceutical compositions comprising thereof and their use |
| EP1408986B1 (en) * | 2001-05-08 | 2008-09-24 | Yale University | Proteomimetic compounds and methods |
| DE10129832A1 (de) | 2001-06-17 | 2003-07-10 | Berolina Drug Dev Ab Svedala | Deuterierte N- und alpha-substituierte Diphenylalkoxyessigsäureaminoalkylester sowie diese Verbindungen enthaltende Arzneimittel |
| JP4455056B2 (ja) * | 2001-07-11 | 2010-04-21 | 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 | 架橋二環式セリンプロテアーゼ阻害剤 |
| DE10162121A1 (de) | 2001-12-12 | 2003-06-18 | Berolina Drug Dev Ab Svedala | Deuterierte substituierte Pyrazolyl-Benzolsulfonamide sowie diese Verbindungen enthaltende Arzneimittel |
| US6867185B2 (en) * | 2001-12-20 | 2005-03-15 | Bristol-Myers Squibb Company | Inhibitors of hepatitis C virus |
| US7119072B2 (en) | 2002-01-30 | 2006-10-10 | Boehringer Ingelheim (Canada) Ltd. | Macrocyclic peptides active against the hepatitis C virus |
| CA2369711A1 (en) | 2002-01-30 | 2003-07-30 | Boehringer Ingelheim (Canada) Ltd. | Macrocyclic peptides active against the hepatitis c virus |
| CA2369970A1 (en) | 2002-02-01 | 2003-08-01 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis c inhibitor tri-peptides |
| US6642204B2 (en) | 2002-02-01 | 2003-11-04 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
| CA2370400A1 (en) | 2002-02-01 | 2003-08-01 | Boehringer Ingelheim (Canada) Ltd. | Hepatitis c inhibitor tri-peptides |
| US7091184B2 (en) | 2002-02-01 | 2006-08-15 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
| US6828301B2 (en) | 2002-02-07 | 2004-12-07 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for hepatitis C viral protease inhibitors |
| CA2481369C (en) * | 2002-04-11 | 2012-07-10 | Vertex Pharmaceuticals Incorporated | Inhibitors of serine proteases, particularly hepatitis c virus ns3 - ns4 protease |
| TWI332956B (en) * | 2002-04-26 | 2010-11-11 | Gilead Sciences Inc | Cellular accumulation of phosphonate analogs of hiv protease inhibitor compounds |
| US6869964B2 (en) * | 2002-05-20 | 2005-03-22 | Bristol-Myers Squibb Company | Heterocyclicsulfonamide hepatitis C virus inhibitors |
| WO2004043339A2 (en) * | 2002-05-20 | 2004-05-27 | Bristol-Myers Squibb Company | Substituted cycloalkyl p1' hepatitis c virus inhibitors |
| US7041698B2 (en) * | 2002-05-20 | 2006-05-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| MY140680A (en) * | 2002-05-20 | 2010-01-15 | Bristol Myers Squibb Co | Hepatitis c virus inhibitors |
| JP3598381B2 (ja) | 2002-07-02 | 2004-12-08 | 独立行政法人物質・材料研究機構 | 一般式；ＢＮで示され、六方晶系５Ｈ型ないしは６Ｈ型多形構造を有し、紫外域で発光するｓｐ３結合型窒化ホウ素とその製造方法、及びこれを利用した機能性材料 |
| US20040138109A1 (en) * | 2002-09-30 | 2004-07-15 | Boehringer Ingelheim Pharmaceuticals, Inc. | Potent inhibitor of HCV serine protease |
| PL199412B1 (pl) * | 2002-10-15 | 2008-09-30 | Boehringer Ingelheim Int | Nowe kompleksy rutenu jako (pre)katalizatory reakcji metatezy, pochodne 2-alkoksy-5-nitrostyrenu jako związki pośrednie i sposób ich wytwarzania |
| US7601709B2 (en) | 2003-02-07 | 2009-10-13 | Enanta Pharmaceuticals, Inc. | Macrocyclic hepatitis C serine protease inhibitors |
| US20040180815A1 (en) | 2003-03-07 | 2004-09-16 | Suanne Nakajima | Pyridazinonyl macrocyclic hepatitis C serine protease inhibitors |
| WO2004101605A1 (en) | 2003-03-05 | 2004-11-25 | Boehringer Ingelheim International Gmbh | Hepatitis c inhibiting compounds |
| UY28240A1 (es) | 2003-03-27 | 2004-11-08 | Boehringer Ingelheim Pharma | Fases cristalinas de un potente inhibidor de la hcv |
| BRPI0409068A (pt) | 2003-04-02 | 2006-03-28 | Boehringer Ingelheim Int | composições farmacêuticas para inibidores de protease viral de hepatite c. |
| EP1615947A2 (en) * | 2003-04-10 | 2006-01-18 | Boehringer Ingelheim International GmbH | Process for preparing macrocyclic compounds |
| TW200510391A (en) * | 2003-04-11 | 2005-03-16 | Vertex Pharma | Inhibitors of serine proteases, particularly HCV NS3-NS4A protease |
| DE602004019518D1 (de) * | 2003-04-16 | 2009-04-02 | Bristol Myers Squibb Co | Makrocyclische isochinolinpeptidinhibitoren des hepatitis-c-virus |
| AU2004233898B2 (en) | 2003-04-25 | 2010-12-23 | Gilead Sciences, Inc. | Antiviral phosphonate analogs |
| WO2004096285A2 (en) | 2003-04-25 | 2004-11-11 | Gilead Sciences, Inc. | Anti-infective phosphonate conjugates |
| WO2004099134A2 (en) | 2003-05-05 | 2004-11-18 | Prosidion Ltd. | Glutaminyl based dp iv-inhibitors |
| EP4032897B1 (en) * | 2003-05-30 | 2025-01-29 | Gilead Pharmasset LLC | Modified fluorinated nucleoside analogues |
| US7273851B2 (en) | 2003-06-05 | 2007-09-25 | Enanta Pharmaceuticals, Inc. | Tri-peptide hepatitis C serine protease inhibitors |
| US7125845B2 (en) * | 2003-07-03 | 2006-10-24 | Enanta Pharmaceuticals, Inc. | Aza-peptide macrocyclic hepatitis C serine protease inhibitors |
| AU2004274468B2 (en) * | 2003-09-18 | 2009-07-23 | Vertex Pharmaceuticals, Incorporated | Inhibitors of serine proteases, particularly HCV NS3-NS4A protease |
| MXPA06004006A (es) * | 2003-10-10 | 2006-06-28 | Vertex Pharma | Inhibidores de serina proteasas, especialmente de ns3-ns4a proteasa del virus de la hepatitis c. |
| US7491794B2 (en) * | 2003-10-14 | 2009-02-17 | Intermune, Inc. | Macrocyclic compounds as inhibitors of viral replication |
| CN103145715B (zh) * | 2003-10-14 | 2016-08-03 | F·霍夫曼-罗须公司 | 作为hcv复制抑制剂的巨环羧酸和酰基磺酰胺 |
| JP4890254B2 (ja) * | 2003-10-27 | 2012-03-07 | 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 | Ｈｃｖｎｓ３−ｎｓ４ａプロテアーゼ耐性突然変異体 |
| US7132504B2 (en) | 2003-11-12 | 2006-11-07 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| EP1687021B1 (en) * | 2003-11-20 | 2013-11-06 | Boehringer Ingelheim International GmbH | Method of removing transition metals, especially from metathesis reaction products |
| US7309708B2 (en) * | 2003-11-20 | 2007-12-18 | Birstol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CA2549167A1 (en) | 2003-12-11 | 2005-06-30 | Schering Corporation | Inhibitors of hepatitis c virus ns3/ns4a serine protease |
| JP4682155B2 (ja) | 2004-01-21 | 2011-05-11 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃ型肝炎ウイルスに対して活性な大環状ペプチド |
| SI1713823T1 (sl) | 2004-01-30 | 2010-04-30 | Medivir Ab | Inhibitorji HCV NS-3 serin proteaze |
| JP2008505849A (ja) | 2004-02-04 | 2008-02-28 | 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 | セリンプロテアーゼ、特に、ｈｃｖ、ｎｓ３−ｎｓ４ａプロテアーゼの阻害剤 |
| CN1972956A (zh) | 2004-02-27 | 2007-05-30 | 先灵公司 | 用作丙型肝炎病毒ns3丝氨酸蛋白酶抑制剂的新化合物 |
| ATE514691T1 (de) | 2004-02-27 | 2011-07-15 | Schering Corp | Neue ketoamide mit cyclischen p4 als inhibitoren der ns3-serinprotease von hepatitis-c-virus |
| TW200536528A (en) | 2004-02-27 | 2005-11-16 | Schering Corp | Novel inhibitors of hepatitis C virus NS3 protease |
| AR048413A1 (es) | 2004-02-27 | 2006-04-26 | Schering Corp | Compuestos prolina 3,4- (ciclopentil) - fusionados , como inhibidores de serina proteasa ns3 del virus de la hepatitis c |
| US7816326B2 (en) | 2004-02-27 | 2010-10-19 | Schering Corporation | Sulfur compounds as inhibitors of hepatitis C virus NS3 serine protease |
| MXPA06010389A (es) | 2004-03-15 | 2007-01-19 | Boehringer Ingelheim Int | Procedimiento para preparar dipeptidos macrociclicos los cuales son adecuados para el tratamiento de infecciones virales de hepatitis c. |
| MXPA06013404A (es) | 2004-05-20 | 2007-01-23 | Schering Corp | Prolinas sustituidas como inhibidores de serina proteasa ns3 de virus de hepatitis c. |
| JP5156374B2 (ja) | 2004-05-25 | 2013-03-06 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 非環式ｈｃｖプロテアーゼインヒビターの調製方法 |
| US7939538B2 (en) * | 2004-06-28 | 2011-05-10 | Amgen Inc. | Compounds, compositions and methods for prevention and treatment of inflammatory and immunoregulatory disorders and diseases |
| DE102004033312A1 (de) * | 2004-07-08 | 2006-01-26 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Kontinuierliches Metatheseverfahren mit Ruthenium-Katalysatoren |
| EP2316839B1 (en) * | 2004-07-16 | 2014-03-12 | Gilead Sciences, Inc. | Antiviral heterocyclic compounds having phosphonate groups |
| CA2573346C (en) * | 2004-07-20 | 2011-09-20 | Boehringer Ingelheim International Gmbh | Hepatitis c inhibitor peptide analogs |
| WO2006026352A1 (en) * | 2004-08-27 | 2006-03-09 | Schering Corporation | Acylsulfonamide compounds as inhibitors of hepatitis c virus ns3 serine protease |
| WO2006033851A1 (en) * | 2004-09-17 | 2006-03-30 | Boehringer Ingelheim International, Gmbh | Ring-closing metathesis process in supercritical fluid |
| US7323447B2 (en) | 2005-02-08 | 2008-01-29 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7524831B2 (en) | 2005-03-02 | 2009-04-28 | Schering Corporation | Treatments for Flaviviridae virus infection |
| AU2006220887B2 (en) | 2005-03-04 | 2010-11-04 | The Rockefeller University | Infectious, chimeric Hepatitis C Virus, methods of producing the same and methods of use thereof |
| WO2006096652A2 (en) | 2005-03-08 | 2006-09-14 | Boehringer Ingelheim International Gmbh | Process for preparing macrocyclic compounds |
| AU2006242475B2 (en) * | 2005-05-02 | 2011-07-07 | Merck Sharp & Dohme Corp. | HCV NS3 protease inhibitors |
| CN101184771A (zh) | 2005-05-26 | 2008-05-21 | 先灵公司 | 干扰素－IgG融合体 |
| US20060275366A1 (en) | 2005-06-02 | 2006-12-07 | Schering Corporation | Controlled-release formulation |
| WO2006130627A2 (en) | 2005-06-02 | 2006-12-07 | Schering Corporation | Methods for treating hepatitis c |
| US7608592B2 (en) * | 2005-06-30 | 2009-10-27 | Virobay, Inc. | HCV inhibitors |
| US7601686B2 (en) * | 2005-07-11 | 2009-10-13 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| TWI389908B (zh) * | 2005-07-14 | 2013-03-21 | Gilead Sciences Inc | 抗病毒化合物類 |
| US7470664B2 (en) * | 2005-07-20 | 2008-12-30 | Merck & Co., Inc. | HCV NS3 protease inhibitors |
| DK1912997T3 (da) * | 2005-07-29 | 2012-01-02 | Tibotec Pharm Ltd | Makrocycliske inhibitorer af hepatitis C virus |
| UA93990C2 (ru) * | 2005-10-11 | 2011-03-25 | Интермюн, Инк. | Соединения и способ ингибирования репликации вируса гепатита c |
| US7772183B2 (en) * | 2005-10-12 | 2010-08-10 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7741281B2 (en) * | 2005-11-03 | 2010-06-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7705138B2 (en) | 2005-11-11 | 2010-04-27 | Vertex Pharmaceuticals Incorporated | Hepatitis C virus variants |
| JP2009515925A (ja) * | 2005-11-16 | 2009-04-16 | エフ．ホフマン−ラ ロシュ アーゲー | 凝固第Ｘａ因子のインヒビターとしての新規なピロリジン誘導体 |
| CA2632626C (en) * | 2005-12-09 | 2011-10-11 | F. Hoffmann-La Roche Ag | Ester prodrugs of 2'-fluoro-2'-alkyl-2'-deoxycytidines and their use in the treatment of hcv infection |
| US7728148B2 (en) * | 2006-06-06 | 2010-06-01 | Enanta Pharmaceuticals, Inc. | Acyclic oximyl hepatitis C protease inhibitors |
| US9526769B2 (en) | 2006-06-06 | 2016-12-27 | Enanta Pharmaceuticals, Inc. | Macrocylic oximyl hepatitis C protease inhibitors |
| WO2007145894A2 (en) | 2006-06-08 | 2007-12-21 | Merck & Co., Inc. | A rapid method to determine inhibitor sensitivity of ns3/4a protease sequences |
| TWI454264B (zh) | 2006-06-26 | 2014-10-01 | Enanta Pharm Inc | 喹啉基巨環ｃ型肝炎病毒絲胺酸蛋白酶抑制劑 |
| KR20090024834A (ko) * | 2006-07-05 | 2009-03-09 | 인터뮨, 인크. | Ｃ형 간염 바이러스 복제의 신규 억제제 |
| US8338593B2 (en) * | 2006-07-07 | 2012-12-25 | Gilead Sciences, Inc. | Modulators of toll-like receptor 7 |
| US7935670B2 (en) * | 2006-07-11 | 2011-05-03 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| EP2374812B1 (en) * | 2006-07-13 | 2015-04-15 | Achillion Pharmaceuticals, Inc. | 4-amino-4-oxobutanoyl Peptides as Inhibitors of Viral Replication |
| US7718612B2 (en) * | 2007-08-02 | 2010-05-18 | Enanta Pharmaceuticals, Inc. | Pyridazinonyl macrocyclic hepatitis C serine protease inhibitors |
| US20090035267A1 (en) * | 2007-07-31 | 2009-02-05 | Moore Joel D | Acyclic, pyridazinone-derived hepatitis c serine protease inhibitors |
| US7635683B2 (en) * | 2006-08-04 | 2009-12-22 | Enanta Pharmaceuticals, Inc. | Quinoxalinyl tripeptide hepatitis C virus inhibitors |
| WO2008019289A2 (en) * | 2006-08-04 | 2008-02-14 | Enanta Pharmaceuticals, Inc. | Tetrazolyl macrocyclic hepatitis c serine protease inhibitors |
| US7605126B2 (en) * | 2006-08-11 | 2009-10-20 | Enanta Pharmaceuticals, Inc. | Acylaminoheteroaryl hepatitis C virus protease inhibitors |
| US20090035268A1 (en) * | 2007-08-01 | 2009-02-05 | Ying Sun | Tetrazolyl acyclic hepatitis c serine protease inhibitors |
| US20090098085A1 (en) * | 2006-08-11 | 2009-04-16 | Ying Sun | Tetrazolyl acyclic hepatitis c serine protease inhibitors |
| US20080038225A1 (en) * | 2006-08-11 | 2008-02-14 | Ying Sun | Triazolyl acyclic hepatitis c serine protease inhibitors |
| US7687459B2 (en) * | 2006-08-11 | 2010-03-30 | Enanta Pharmaceuticals, Inc. | Arylalkoxyl hepatitis C virus protease inhibitors |
| US7662779B2 (en) * | 2006-08-11 | 2010-02-16 | Enanta Pharmaceuticals, Inc. | Triazolyl macrocyclic hepatitis C serine protease inhibitors |
| US20120220520A1 (en) * | 2006-10-17 | 2012-08-30 | Van T Klooster Gerben Albert Eleutherius | Bioavailable combinations for hcv treatment |
| US8343477B2 (en) * | 2006-11-01 | 2013-01-01 | Bristol-Myers Squibb Company | Inhibitors of hepatitis C virus |
| US20080107623A1 (en) * | 2006-11-01 | 2008-05-08 | Bristol-Myers Squibb Company | Inhibitors of Hepatitis C Virus |
| US20080107625A1 (en) * | 2006-11-01 | 2008-05-08 | Bristol-Myers Squibb Company | Inhibitors of Hepatitis C Virus |
| US7772180B2 (en) * | 2006-11-09 | 2010-08-10 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CN101535294B (zh) | 2006-11-17 | 2014-09-24 | 泰博特克药品有限公司 | 丙型肝炎病毒的大环化合物抑制剂 |
| US7951789B2 (en) | 2006-12-28 | 2011-05-31 | Idenix Pharmaceuticals, Inc. | Compounds and pharmaceutical compositions for the treatment of viral infections |
| CA2676297A1 (en) * | 2007-02-16 | 2008-08-21 | Boehringer Ingelheim International Gmbh | Inhibitors of hepatitis c ns3 protease |
| CN101679240A (zh) * | 2007-03-23 | 2010-03-24 | 先灵公司 | Hcv ns3蛋白酶的p1-非可差向异构化酮酰胺抑制剂 |
| CN101663294A (zh) | 2007-04-24 | 2010-03-03 | 弗·哈夫曼-拉罗切有限公司 | Hcv蛋白酶抑制剂中间体的制备方法 |
| WO2008134395A1 (en) | 2007-04-26 | 2008-11-06 | Enanta Pharmaceuticals, Inc. | Aza-peptide macrocyclic hepatitis c serine protease inhibitors |
| US8377872B2 (en) | 2007-04-26 | 2013-02-19 | Enanta Pharmaceuticals, Inc. | Cyclic P3 tripeptide hepatitis C serine protease inhibitors |
| US7910587B2 (en) | 2007-04-26 | 2011-03-22 | Enanta Pharmaceuticals, Inc. | Quinoxalinyl dipeptide hepatitis C virus inhibitors |
| US20090123423A1 (en) * | 2007-04-26 | 2009-05-14 | Yonghua Gai | Hydroxyamic analogs as hepatitis c virus serine protease inhibitor |
| US20080317712A1 (en) | 2007-04-26 | 2008-12-25 | Deqiang Niu | Arylpiperidinyl and arylpyrrolidinyl tripeptide hepatitis c serine protease inhibitors |
| US20080279821A1 (en) | 2007-04-26 | 2008-11-13 | Deqiang Niu | Arylpiperidinyl and arylpyrrolidinyl macrocyclic hepatitis c serine protease inhibitors |
| US20080274082A1 (en) | 2007-04-26 | 2008-11-06 | Yonghua Gai | Oximyl hydroxyamic analogs as hepatitis c virus protease inhibitor |
| US20080267917A1 (en) | 2007-04-26 | 2008-10-30 | Deqiang Niu | N-functionalized amides as hepatitis c serine protease inhibitors |
| US7906513B2 (en) | 2007-04-26 | 2011-03-15 | Enanta Pharmaceuticals, Inc. | Hydrazide-containing hepatitis C serine protease inhibitors |
| US20090155209A1 (en) * | 2007-05-03 | 2009-06-18 | Blatt Lawrence M | Novel macrocyclic inhibitors of hepatitis c virus replication |
| AP2009005057A0 (en) | 2007-05-10 | 2009-12-31 | Array Biopharma Inc | Novel peptide inhibitors of hepatitis c virus replication |
| US20090005387A1 (en) * | 2007-06-26 | 2009-01-01 | Deqiang Niu | Quinoxalinyl macrocyclic hepatitis c virus serine protease inhibitors |
| WO2009014730A1 (en) * | 2007-07-26 | 2009-01-29 | Idenix Pharmaceuticals, Inc. | Macrocyclic serine protease inhibitors |
| US20090053175A1 (en) * | 2007-08-24 | 2009-02-26 | Yat Sun Or | Substitute pyrrolidine derivatives |
| US20090060874A1 (en) * | 2007-09-05 | 2009-03-05 | Yao-Ling Qiu | Bicyclic pyrrolidine derivatives |
| US8163693B2 (en) * | 2007-09-24 | 2012-04-24 | Achillion Pharmaceuticals, Inc. | Urea-containing peptides as inhibitors of viral replication |
| US20090082366A1 (en) * | 2007-09-26 | 2009-03-26 | Protia, Llc | Deuterium-enriched telaprevir |
| WO2009055335A2 (en) * | 2007-10-25 | 2009-04-30 | Taigen Biotechnology Co., Ltd. | Hcv protease inhibitors |
| US8383583B2 (en) * | 2007-10-26 | 2013-02-26 | Enanta Pharmaceuticals, Inc. | Macrocyclic, pyridazinone-containing hepatitis C serine protease inhibitors |
| US8426360B2 (en) * | 2007-11-13 | 2013-04-23 | Enanta Pharmaceuticals, Inc. | Carbocyclic oxime hepatitis C virus serine protease inhibitors |
| WO2009076166A2 (en) * | 2007-12-05 | 2009-06-18 | Enanta Pharmaceuticals, Inc. | Oximyl hcv serine protease inhibitors |
| US8283309B2 (en) | 2007-12-20 | 2012-10-09 | Enanta Pharmaceuticals, Inc. | Bridged carbocyclic oxime hepatitis C virus serine protease inhibitors |
| CN101903391B (zh) * | 2007-12-21 | 2013-04-03 | 弗·哈夫曼-拉罗切有限公司 | 大环化合物的制备方法 |
| EP2250174B1 (en) | 2008-02-04 | 2013-08-28 | IDENIX Pharmaceuticals, Inc. | Macrocyclic serine protease inhibitors |
| EA201001262A1 (ru) | 2008-02-07 | 2011-04-29 | Вайробей, Инк. | Ингибиторы катепсина в |
| ES2388994T3 (es) | 2008-04-11 | 2012-10-22 | F. Hoffmann-La Roche Ag | Nuevos complejos de rutenio, como catalizadores para reacciones de metátesis |
| KR20110005869A (ko) | 2008-04-15 | 2011-01-19 | 인터뮨, 인크. | Ｃ형 간염 바이러스 복제의 신규한 마크로사이클릭 억제제 |
| US8211891B2 (en) | 2008-04-30 | 2012-07-03 | Enanta Pharmaceuticals, Inc. | Difluoromethyl-containing macrocyclic compounds as hepatitis C virus inhibitors |
| US20090285773A1 (en) | 2008-05-15 | 2009-11-19 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US20090285774A1 (en) | 2008-05-15 | 2009-11-19 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| CN101580535B (zh) | 2008-05-16 | 2012-10-03 | 太景生物科技股份有限公司 | 丙型肝炎病毒蛋白酶抑制剂 |
| JP5529120B2 (ja) | 2008-05-29 | 2014-06-25 | ブリストル−マイヤーズ スクイブ カンパニー | Ｃ型肝炎ウイルス阻害剤 |
| KR20110065440A (ko) * | 2008-07-02 | 2011-06-15 | 아이데닉스 파마슈티칼스, 인코포레이티드 | 바이러스 감염의 치료를 위한 화합물 및 제약 조성물 |
| US7906655B2 (en) * | 2008-08-07 | 2011-03-15 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| AU2009278075B2 (en) * | 2008-08-07 | 2013-07-04 | F. Hoffmann-La Roche Ag | Process for the preparation of a macrocycle |
| WO2010033443A1 (en) * | 2008-09-17 | 2010-03-25 | Boehringer Ingelheim International Gmbh | Combination of hcv ns3 protease inhibitor with interferon and ribavirin |
| US8603737B2 (en) * | 2008-09-19 | 2013-12-10 | Celgene Avilomics Research, Inc. | Methods for identifying HCV protease inhibitors |
| US20100080770A1 (en) * | 2008-09-29 | 2010-04-01 | Bristol-Myers Squibb Company | Hepatitis C Virus Inhibitors |
| US8563505B2 (en) | 2008-09-29 | 2013-10-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8044087B2 (en) | 2008-09-29 | 2011-10-25 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| EA201170441A1 (ru) * | 2008-10-15 | 2012-05-30 | Интермьюн, Инк. | Терапевтические противовирусные пептиды |
| US8445430B2 (en) * | 2008-11-20 | 2013-05-21 | Achillion Pharmaceuticals, Inc. | Cyclic carboxamide compounds and analogues thereof as of hepatitis C virus |
| JP5669749B2 (ja) * | 2008-12-10 | 2015-02-12 | アキリオン ファーマシューティカルズ，インコーポレーテッド | ウイルス複製の阻害剤である４−アミノ−４−オキソブタノイルペプチド環状類似体 |
| US8283310B2 (en) * | 2008-12-15 | 2012-10-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| UY32325A (es) * | 2008-12-19 | 2010-07-30 | Gilead Sciences Inc | Inhibidores de ns3 proteasa del vhc |
| EP2367813A1 (en) | 2008-12-22 | 2011-09-28 | Gilead Sciences, Inc. | Antiviral compounds |
| EP2393493A4 (en) | 2009-01-30 | 2013-07-17 | Glaxosmithkline Llc | LINKS |
| TWI438200B (zh) | 2009-02-17 | 2014-05-21 | 必治妥美雅史谷比公司 | Ｃ型肝炎病毒抑制劑 |
| AR075584A1 (es) | 2009-02-27 | 2011-04-20 | Intermune Inc | COMPOSICIONES TERAPEUTICAS QUE COMPRENDEN beta-D-2'-DESOXI-2'-FLUORO-2'-C-METILCITIDINA Y UN DERIVADO DE ACIDO ISOINDOL CARBOXILICO Y SUS USOS. COMPUESTO. |
| US8377962B2 (en) | 2009-04-08 | 2013-02-19 | Idenix Pharmaceuticals, Inc. | Macrocyclic serine protease inhibitors |
| US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
| EP2421527B1 (en) | 2009-04-25 | 2018-06-13 | F.Hoffmann-La Roche Ag | Methods for improving pharmacokinetics |
| US20100323989A1 (en) | 2009-06-23 | 2010-12-23 | Gilead Sciences, Inc. | Pharmaceutical combinations useful for treating hcv |
| UY32720A (es) | 2009-06-23 | 2011-01-31 | Gilead Sciences Inc | Combinaciones farmaceuticas utiles para el tratamiento del virus de la hepatitis c (vhc), usos y metodos relacionados |
| US20100324059A1 (en) | 2009-06-23 | 2010-12-23 | Gilead Sciences, Inc. | Pharmaceutical compositions useful for treating hcv |
| US8232246B2 (en) | 2009-06-30 | 2012-07-31 | Abbott Laboratories | Anti-viral compounds |
| US20110129444A1 (en) | 2009-09-28 | 2011-06-02 | Intermune, Inc | Novel macrocyclic inhibitors of hepatitis c virus replication |
-
2010
- 2010-02-23 AR ARP100100517A patent/AR075584A1/es unknown
- 2010-02-26 US US13/203,334 patent/US20120128628A1/en not_active Abandoned
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- 2011-08-21 IL IL214760A patent/IL214760A0/en unknown
- 2011-08-23 CR CR20110453A patent/CR20110453A/es not_active Application Discontinuation
- 2011-08-25 CO CO11108893A patent/CO6410304A2/es not_active Application Discontinuation
- 2011-08-26 EC EC2011011292A patent/ECSP11011292A/es unknown
- 2011-08-26 CL CL2011002082A patent/CL2011002082A1/es unknown
-
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- 2015-03-03 JP JP2015041648A patent/JP2015098501A/ja not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008506648A (ja) * | 2004-07-14 | 2008-03-06 | ノバルティス アクチエンゲゼルシャフト | Ｃ型肝炎（ｈｃｖ）処置のためのシクロスポリンとペグ化インターフェロンの組合せ剤の使用 |
| JP2009502920A (ja) * | 2005-07-25 | 2009-01-29 | インターミューン・インコーポレーテッド | Ｃ型肝炎ウイルス複製の新規大環状阻害剤 |
| WO2008144072A1 (en) * | 2007-05-21 | 2008-11-27 | Vertex Pharmaceuticals Incorporated | Dose forms comprising vx- 950 and their dosage regimen |
Non-Patent Citations (4)
| Title |
|---|
| 59TH ANNUAL MEETING OF THE AMERICAN ASSOCIATION FOR THE STUDY OF LIVER DISEASES, JPN6014011433, 2008, pages 1885, ISSN: 0002771270 * |
| ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 52(12), JPN6014011424, 2008, pages 4356 - 4369, ISSN: 0002771271 * |
| HEPATOLOGY, vol. 46(4)Suppl.1, JPN6014011429, 2007, pages 862 - 8, ISSN: 0002771273 * |
| JOURNAL OF HEPATOLOGY, vol. 48, JPN6014011428, 2008, pages 29 - 65, ISSN: 0002771272 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015528511A (ja) * | 2012-09-18 | 2015-09-28 | アッヴィ・インコーポレイテッド | Ｃ型肝炎を治療するための方法 |
| JP2018109035A (ja) * | 2012-09-18 | 2018-07-12 | アッヴィ・インコーポレイテッド | Ｃ型肝炎を治療するための方法 |
| JP2019194241A (ja) * | 2012-09-18 | 2019-11-07 | アッヴィ・インコーポレイテッド | Ｃ型肝炎を治療するための方法 |
| JP2021054849A (ja) * | 2012-09-18 | 2021-04-08 | アッヴィ・インコーポレイテッド | Ｃ型肝炎を治療するための方法 |
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| CL2011002082A1 (es) | 2012-04-13 |
| WO2010099458A1 (en) | 2010-09-02 |
| US20100221217A1 (en) | 2010-09-02 |
| MX2011008980A (es) | 2011-11-18 |
| CN102361641A (zh) | 2012-02-22 |
| US8735345B2 (en) | 2014-05-27 |
| KR20110135941A (ko) | 2011-12-20 |
| AR075584A1 (es) | 2011-04-20 |
| MA33236B1 (fr) | 2012-05-02 |
| IL214760A0 (en) | 2011-11-30 |
| BRPI1009338A2 (pt) | 2016-11-01 |
| NZ594524A (en) | 2013-09-27 |
| US20120128628A1 (en) | 2012-05-24 |
| JP2015098501A (ja) | 2015-05-28 |
| PE20120777A1 (es) | 2012-06-27 |
| CO6410304A2 (es) | 2012-03-30 |
| TW201035099A (en) | 2010-10-01 |
| SG173774A1 (en) | 2011-09-29 |
| CA2751220A1 (en) | 2010-09-02 |
| RU2011139180A (ru) | 2013-04-10 |
| AU2010217818A1 (en) | 2011-08-18 |
| CR20110453A (es) | 2011-12-08 |
| TWI473810B (zh) | 2015-02-21 |
| EP2400966A1 (en) | 2012-01-04 |
| ECSP11011292A (es) | 2011-12-30 |
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