CN101773661B - 用于治疗和预防丙型肝炎病毒感染的3-醚和3-硫醚取代的环孢菌素衍生物 - Google Patents
用于治疗和预防丙型肝炎病毒感染的3-醚和3-硫醚取代的环孢菌素衍生物 Download PDFInfo
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- CN101773661B CN101773661B CN2010100010787A CN201010001078A CN101773661B CN 101773661 B CN101773661 B CN 101773661B CN 2010100010787 A CN2010100010787 A CN 2010100010787A CN 201010001078 A CN201010001078 A CN 201010001078A CN 101773661 B CN101773661 B CN 101773661B
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
- A61K38/13—Cyclosporins
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
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- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
- C07K7/645—Cyclosporins; Related peptides
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Organic Chemistry (AREA)
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- Pulmonology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US61515204P | 2004-10-01 | 2004-10-01 | |
| US60/615,152 | 2004-10-01 | ||
| US70762605P | 2005-08-11 | 2005-08-11 | |
| US60/707,626 | 2005-08-11 |
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| CN2005800412034A Division CN101068829B (zh) | 2004-10-01 | 2005-09-30 | 用于治疗和预防丙型肝炎病毒感染的3-醚和3-硫醚取代的环孢菌素衍生物 |
Publications (2)
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|---|---|
| CN101773661A CN101773661A (zh) | 2010-07-14 |
| CN101773661B true CN101773661B (zh) | 2013-09-25 |
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| CN2010100010787A Expired - Fee Related CN101773661B (zh) | 2004-10-01 | 2005-09-30 | 用于治疗和预防丙型肝炎病毒感染的3-醚和3-硫醚取代的环孢菌素衍生物 |
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| EP (1) | EP1802650B1 (enExample) |
| JP (2) | JP5139065B2 (enExample) |
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| AT (1) | ATE530561T1 (enExample) |
| AU (1) | AU2005292162B2 (enExample) |
| BR (1) | BRPI0516737A (enExample) |
| CA (1) | CA2583494C (enExample) |
| DK (1) | DK1802650T3 (enExample) |
| ES (1) | ES2373450T3 (enExample) |
| IL (1) | IL182315A (enExample) |
| MX (1) | MX2007003538A (enExample) |
| NZ (1) | NZ554514A (enExample) |
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| PT (1) | PT1802650E (enExample) |
| RU (1) | RU2399628C2 (enExample) |
| SI (1) | SI1802650T1 (enExample) |
| WO (1) | WO2006039668A2 (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7196161B2 (en) | 2004-10-01 | 2007-03-27 | Scynexis Inc. | 3-ether and 3-thioether substituted cyclosporin derivatives for the treatment and prevention of hepatitis C infection |
| WO2006054801A1 (en) | 2004-11-22 | 2006-05-26 | Astellas Pharma Inc. | New cyclic peptide compound |
| JP5322647B2 (ja) * | 2005-09-30 | 2013-10-23 | スシネキス インク | ウイルス感染の治療及び予防のためのシクロスポリンａのアリールアルキル及びヘテロアリールアルキル誘導体 |
| US7754685B2 (en) * | 2005-09-30 | 2010-07-13 | Scynexis, Inc. | Methods and pharmaceutical compositions for the treatment and prevention of hepatitis C infection |
| US7872097B2 (en) | 2005-10-26 | 2011-01-18 | Astellas Pharma Inc. | Cyclic peptide compounds |
| US7825152B2 (en) | 2006-04-11 | 2010-11-02 | Novartis Ag | Organic compounds and their uses |
| US8188052B2 (en) * | 2006-05-19 | 2012-05-29 | Scynexis, Inc. | Method for the treatment and prevention of ocular disorders |
| KR101089112B1 (ko) * | 2006-06-02 | 2011-12-06 | 피씨 제스띠옹 에스.아.에스. | 활성 전자 관리 |
| SG175621A1 (en) * | 2006-10-12 | 2011-11-28 | Novartis Ag | Use of modified cyclosporins |
| WO2008069917A2 (en) | 2006-11-20 | 2008-06-12 | Scynexis, Inc. | Novel cyclic peptides |
| WO2008127613A1 (en) * | 2007-04-11 | 2008-10-23 | Scynexis, Inc. | New pharmaceutical compositions |
| US8603975B2 (en) | 2007-05-02 | 2013-12-10 | Astellas Pharma Inc. | Cyclic peptide compounds |
| US20090306033A1 (en) * | 2008-06-06 | 2009-12-10 | Keqiang Li | Novel cyclic peptides |
| CA2724523A1 (en) * | 2008-06-06 | 2010-01-07 | Scynexis, Inc. | Novel macrocyclic peptides |
| JP5726733B2 (ja) | 2008-07-30 | 2015-06-03 | シクロフィリン ファーマシューティカルズ コープ． | 非免疫抑制性シクロスポリン類似体分子 |
| WO2010076329A1 (en) | 2008-12-31 | 2010-07-08 | Scynexis, Inc. | Derivatives of cyclosporin a |
| MX2011007195A (es) * | 2009-01-07 | 2013-07-12 | Scynexis Inc | Derivado de ciclosporina para el uso en el tratamiento de infección de virus de hepatitis c (vhc) y virus de inmunodeficiencia humana (vih). |
| CA2751210C (en) * | 2009-01-30 | 2015-04-21 | Enanta Pharmaceuticals, Inc. | Cyclosporin analogues for preventing or treating hepatitis c infection |
| US8481483B2 (en) | 2009-02-19 | 2013-07-09 | Enanta Pharmaceuticals, Inc. | Cyclosporin analogues |
| US8512690B2 (en) | 2009-04-10 | 2013-08-20 | Novartis Ag | Derivatised proline containing peptide compounds as protease inhibitors |
| US20110182850A1 (en) | 2009-04-10 | 2011-07-28 | Trixi Brandl | Organic compounds and their uses |
| US8685917B2 (en) | 2009-07-09 | 2014-04-01 | Enanta Pharmaceuticals, Inc. | Cyclosporin analogues |
| US8367053B2 (en) | 2009-07-09 | 2013-02-05 | Enanta Pharmaceuticals, Inc. | Cyclosporin analogues |
| US8349312B2 (en) | 2009-07-09 | 2013-01-08 | Enanta Pharmaceuticals, Inc. | Proline substituted cyclosporin analogues |
| EA201200650A1 (ru) | 2009-10-30 | 2012-12-28 | Бёрингер Ингельхайм Интернациональ Гмбх | Курсы комбинированного лечения вируса гепатита с, включающие bi201335, интерферон-альфа и рибавирин |
| CA2782898A1 (en) | 2009-12-09 | 2011-06-16 | Scynexis, Inc. | Novel cyclic peptides |
| MX2012007076A (es) * | 2009-12-18 | 2012-07-20 | Boehringer Ingelheim Int | Terapia combinada de hcv. |
| CN102834409A (zh) | 2009-12-30 | 2012-12-19 | 西尼克斯公司 | 环孢菌素类似物 |
| US8623814B2 (en) | 2010-02-23 | 2014-01-07 | Enanta Pharmaceuticals, Inc. | Antiviral agents |
| CN103153329A (zh) | 2010-07-16 | 2013-06-12 | 美国科技环球有限公司 | 新颖的环孢霉素a衍生物在病毒感染的治疗和预防中的应用 |
| CN103153330B (zh) | 2010-08-12 | 2017-08-18 | 美国科技环球有限公司 | 新的环孢霉素衍生物在病毒感染的治疗和预防中的应用 |
| CA2811799A1 (en) | 2010-10-08 | 2012-04-12 | Novartis Ag | Vitamin e formulations of sulfamide ns3 inhibitors |
| ES2625502T3 (es) * | 2010-12-03 | 2017-07-19 | S&T Global Inc | Nuevos derivados de ciclosporina para el tratamiento y prevención de una infección vírica |
| US9890198B2 (en) | 2010-12-03 | 2018-02-13 | S&T Global Inc. | Cyclosporin derivatives and uses thereof |
| TR201900128T4 (tr) | 2010-12-15 | 2019-02-21 | Contravir Pharmaceuticals Inc | Amino asit 1'de ve 3'te modifiye edilmiş siklosporin analoğu moleküller. |
| RU2448690C1 (ru) * | 2011-03-15 | 2012-04-27 | Открытое акционерное общество "Биосинтез" | Твердая лекарственная форма пролонгированного действия нестероидного противовоспалительного средства кетопрофен, способ получения |
| CN103987399A (zh) * | 2011-08-19 | 2014-08-13 | 美国科技环球有限公司 | 用于治疗和预防病毒感染的新型环孢菌素衍生物 |
| US9266927B2 (en) | 2012-06-01 | 2016-02-23 | Allergan, Inc. | Cyclosporin A analogs |
| US8906853B2 (en) | 2012-11-28 | 2014-12-09 | Enanta Pharmaceuticals, Inc. | [N-Me-4-hydroxyleucine]-9-cyclosporin analogues for treatment and prevention of hepatitis C infection |
| US20140205566A1 (en) | 2012-11-30 | 2014-07-24 | Novartis Ag | Cyclic nucleuoside derivatives and uses thereof |
| EP3038626A4 (en) * | 2013-08-26 | 2017-04-19 | Enanta Pharmaceuticals, Inc. | Cyclosporin analogues for preventing or treating hepatitis c |
| WO2016073480A1 (en) | 2014-11-03 | 2016-05-12 | Enanta Pharmaceuticals, Inc. | Novel cyclosporin analogues for preventing or treating hepatitis c infection |
| US9914755B2 (en) | 2015-01-08 | 2018-03-13 | Allergan, Inc. | Cyclosporin derivatives wherein the MeBmt sidechain has been cyclized |
| WO2016160362A1 (en) | 2015-03-31 | 2016-10-06 | Allergan, Inc. | Cyclosporins modified on the mebmt sidechain by heterocyclic rings |
| CN108025039B (zh) * | 2015-06-30 | 2022-07-29 | 西普拉里斯有限公司 | 新颖的大环化合物 |
| GB201711749D0 (en) * | 2017-07-21 | 2017-09-06 | Cypralis Ltd | Cyclosporin analogues and uses thereof |
| WO2020037530A1 (en) | 2018-08-22 | 2020-02-27 | Waterstone Pharmaceuticals (Wuhan) Co., Ltd. | Crystalline form of compound and uses thereof in medicine |
| JP2022551161A (ja) | 2019-10-12 | 2022-12-07 | ファーサイト メディカル テクノロジー （シャンハイ） カンパニー リミテッド | ネフロトキシン誘発性腎障害の処置及び予防 |
| EP4126905A4 (en) * | 2020-03-26 | 2024-05-29 | Farsight Medical Technology (Shanghai) Co., Ltd. | CYCLOPHILIN INHIBITORS AND THEIR USES |
| WO2021209003A1 (en) * | 2020-04-15 | 2021-10-21 | Farsight Medical Technology (Shanghai) Co., Ltd. | Prevention and treatment of organ injuries |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5994299A (en) * | 1996-12-24 | 1999-11-30 | Rhone-Poulenc Rorer, S.A. | Cyclosporin compounds, their preparation and the pharmaceutical compositions which contain them |
| WO2004041221A1 (en) * | 2002-11-04 | 2004-05-21 | Lg Household & Health Care Ltd. | Use of 3-position cyclosporin derivatives for hair growth |
Family Cites Families (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0194972B1 (en) * | 1985-03-11 | 1992-07-29 | Sandoz Ag | Novel cyclosporins |
| US4814323A (en) * | 1986-03-25 | 1989-03-21 | Andrieu J M | Process for the treatment and the prevention of AIDS and other disorders induced by the LAV/HTLV III virus |
| US4798823A (en) * | 1987-06-03 | 1989-01-17 | Merck & Co., Inc. | New cyclosporin analogs with modified "C-9 amino acids" |
| US4885276A (en) * | 1987-06-03 | 1989-12-05 | Merck & Co., Inc. | Cyclosporin analogs with modified "C-9 amino acids" |
| US4996193A (en) * | 1989-03-03 | 1991-02-26 | The Regents Of The University Of California | Combined topical and systemic method of administration of cyclosporine |
| US5294604A (en) * | 1989-12-20 | 1994-03-15 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating ocular diseases by periocular administration of cyclosporine A or G |
| DE69124459T3 (de) * | 1990-11-02 | 2001-05-31 | Novartis Ag, Basel | Zyklosporine |
| WO1994022896A1 (fr) * | 1993-03-31 | 1994-10-13 | Tokyo Tanabe Company Limited | Ameliorant de la cholestase |
| WO1995003056A1 (en) * | 1993-07-19 | 1995-02-02 | Tokyo Tanabe Company Limited | Hepatitis c virus proliferation inhibitor |
| AU2577295A (en) * | 1994-06-01 | 1995-12-21 | Yuhan Corporation | Cyclosporin containing composition and process for the preparation thereof |
| HUP9900405A3 (en) * | 1995-07-17 | 2001-04-28 | Scynexis Inc Durham | Cyclosporin derivatives with anti-hiv effect |
| JP3089350B2 (ja) * | 1995-11-20 | 2000-09-18 | ギルフォード ファーマシューティカルズ インコーポレイテッド | シクロフィリンロタマーゼ活性の阻害剤 |
| FR2757520B1 (fr) * | 1996-12-24 | 1999-01-29 | Rhone Poulenc Rorer Sa | Derive de cyclosporine, sa preparation et les compositions pharmaceutiques qui le contiennent |
| FR2757522B1 (fr) * | 1996-12-24 | 1999-01-29 | Rhone Poulenc Rorer Sa | Derives de cyclosporine, leur preparation et les compositions pharmaceutiques qui les contiennent |
| FR2762843B1 (fr) * | 1997-04-30 | 1999-12-10 | Rhone Poulenc Rorer Sa | Nouveaux derives de cyclosporine, leur preparation et les compositions pharmaceutiques qui les contiennent |
| CN1205220C (zh) * | 1998-06-12 | 2005-06-08 | 斯－凯穆公司 | 新颖的环孢菌素 |
| FR2780061B1 (fr) * | 1998-06-22 | 2001-09-07 | Rhone Poulenc Rorer Sa | Nouveau procede de preparation de derives de cyclosporine |
| BR9911724A (pt) * | 1998-07-01 | 2001-03-20 | Debiopharm Sa | Ciclosporina que tem um perfil de atividade melhorado |
| US6254860B1 (en) * | 1999-04-13 | 2001-07-03 | Allergan Sales, Inc. | Ocular treatment using cyclosporin-A derivatives |
| US6521595B1 (en) * | 1999-11-19 | 2003-02-18 | Lg Chemical, Ltd. | Nonimmunosuppressive [γ-hydroxy-methylleucine4] cyclosporin A, hair growth stimulator and external composition for skin using the same |
| MY139078A (en) * | 2000-07-21 | 2009-08-28 | Schering Corp | Peptides as ns3-serine protease inhibitors of hepatitis c virus |
| US6987090B2 (en) * | 2002-05-09 | 2006-01-17 | Lg Household & Health Care Ltd. | Use of 3-position cyclosporin derivatives for hair growth |
| GB0320638D0 (en) * | 2003-09-03 | 2003-10-01 | Novartis Ag | Organic compounds |
| US7196161B2 (en) * | 2004-10-01 | 2007-03-27 | Scynexis Inc. | 3-ether and 3-thioether substituted cyclosporin derivatives for the treatment and prevention of hepatitis C infection |
| JP5322647B2 (ja) * | 2005-09-30 | 2013-10-23 | スシネキス インク | ウイルス感染の治療及び予防のためのシクロスポリンａのアリールアルキル及びヘテロアリールアルキル誘導体 |
| US7754685B2 (en) * | 2005-09-30 | 2010-07-13 | Scynexis, Inc. | Methods and pharmaceutical compositions for the treatment and prevention of hepatitis C infection |
| US8188052B2 (en) * | 2006-05-19 | 2012-05-29 | Scynexis, Inc. | Method for the treatment and prevention of ocular disorders |
| WO2008069917A2 (en) * | 2006-11-20 | 2008-06-12 | Scynexis, Inc. | Novel cyclic peptides |
| WO2008127613A1 (en) * | 2007-04-11 | 2008-10-23 | Scynexis, Inc. | New pharmaceutical compositions |
| CA2724523A1 (en) * | 2008-06-06 | 2010-01-07 | Scynexis, Inc. | Novel macrocyclic peptides |
| US20090306033A1 (en) * | 2008-06-06 | 2009-12-10 | Keqiang Li | Novel cyclic peptides |
| WO2010076329A1 (en) * | 2008-12-31 | 2010-07-08 | Scynexis, Inc. | Derivatives of cyclosporin a |
| CN102271688A (zh) * | 2009-01-07 | 2011-12-07 | 西尼克斯公司 | 用于治疗hcv的环孢菌素衍生物和核苷的组合 |
| MX2011007195A (es) * | 2009-01-07 | 2013-07-12 | Scynexis Inc | Derivado de ciclosporina para el uso en el tratamiento de infección de virus de hepatitis c (vhc) y virus de inmunodeficiencia humana (vih). |
| CA2782898A1 (en) * | 2009-12-09 | 2011-06-16 | Scynexis, Inc. | Novel cyclic peptides |
-
2005
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- 2005-09-30 AT AT05815625T patent/ATE530561T1/de active
- 2005-09-30 AU AU2005292162A patent/AU2005292162B2/en not_active Ceased
- 2005-09-30 MX MX2007003538A patent/MX2007003538A/es active IP Right Grant
- 2005-09-30 EP EP05815625A patent/EP1802650B1/en not_active Expired - Lifetime
- 2005-09-30 PT PT05815625T patent/PT1802650E/pt unknown
- 2005-09-30 JP JP2007534872A patent/JP5139065B2/ja not_active Expired - Fee Related
- 2005-09-30 DK DK05815625.8T patent/DK1802650T3/da active
- 2005-09-30 WO PCT/US2005/035533 patent/WO2006039668A2/en not_active Ceased
- 2005-09-30 NZ NZ554514A patent/NZ554514A/en not_active IP Right Cessation
- 2005-09-30 BR BRPI0516737-0A patent/BRPI0516737A/pt not_active IP Right Cessation
- 2005-09-30 ES ES05815625T patent/ES2373450T3/es not_active Expired - Lifetime
- 2005-09-30 SI SI200531452T patent/SI1802650T1/sl unknown
- 2005-09-30 CN CN2010100010787A patent/CN101773661B/zh not_active Expired - Fee Related
- 2005-09-30 RU RU2007116119/04A patent/RU2399628C2/ru not_active IP Right Cessation
- 2005-09-30 KR KR1020077009820A patent/KR101309409B1/ko not_active Expired - Fee Related
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-
2009
- 2009-12-21 US US12/643,860 patent/US20100167996A1/en not_active Abandoned
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2012
- 2012-05-08 JP JP2012106395A patent/JP2012167113A/ja active Pending
- 2012-06-20 US US13/528,165 patent/US20120264679A1/en not_active Abandoned
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5994299A (en) * | 1996-12-24 | 1999-11-30 | Rhone-Poulenc Rorer, S.A. | Cyclosporin compounds, their preparation and the pharmaceutical compositions which contain them |
| WO2004041221A1 (en) * | 2002-11-04 | 2004-05-21 | Lg Household & Health Care Ltd. | Use of 3-position cyclosporin derivatives for hair growth |
Non-Patent Citations (1)
| Title |
|---|
| Nakagawa Mina.Specific inhibition of hepatits C Virus replication by cyclosporin A.《Biochemical and Biophysical Research Communication》.2004,第313卷42-47. * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2006039668A2 (en) | 2006-04-13 |
| US20120264679A1 (en) | 2012-10-18 |
| HK1108703A1 (en) | 2008-05-16 |
| WO2006039668B1 (en) | 2007-05-31 |
| BRPI0516737A (pt) | 2008-04-29 |
| ATE530561T1 (de) | 2011-11-15 |
| PL1802650T3 (pl) | 2012-04-30 |
| ES2373450T3 (es) | 2012-02-03 |
| US20100167996A1 (en) | 2010-07-01 |
| JP2008514732A (ja) | 2008-05-08 |
| EP1802650A2 (en) | 2007-07-04 |
| PT1802650E (pt) | 2011-12-30 |
| JP5139065B2 (ja) | 2013-02-06 |
| AU2005292162A1 (en) | 2006-04-13 |
| KR20070073841A (ko) | 2007-07-10 |
| IL182315A0 (en) | 2007-07-24 |
| AU2005292162B2 (en) | 2011-11-10 |
| NZ554514A (en) | 2010-10-29 |
| KR101309409B1 (ko) | 2013-09-23 |
| DK1802650T3 (da) | 2012-02-06 |
| CN101773661A (zh) | 2010-07-14 |
| RU2399628C2 (ru) | 2010-09-20 |
| RU2007116119A (ru) | 2008-11-10 |
| EP1802650A4 (en) | 2008-08-20 |
| SI1802650T1 (sl) | 2012-03-30 |
| CA2583494C (en) | 2014-01-21 |
| WO2006039668A3 (en) | 2007-04-19 |
| MX2007003538A (es) | 2008-01-16 |
| CA2583494A1 (en) | 2006-04-13 |
| JP2012167113A (ja) | 2012-09-06 |
| EP1802650B1 (en) | 2011-10-26 |
| IL182315A (en) | 2013-08-29 |
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