JP2009501732A - Ｃ型肝炎インヒビターペプチド類似体 - Google Patents
Ｃ型肝炎インヒビターペプチド類似体 Download PDFInfo
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- JP2009501732A JP2009501732A JP2008521756A JP2008521756A JP2009501732A JP 2009501732 A JP2009501732 A JP 2009501732A JP 2008521756 A JP2008521756 A JP 2008521756A JP 2008521756 A JP2008521756 A JP 2008521756A JP 2009501732 A JP2009501732 A JP 2009501732A
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- alkyl
- compound
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- infection
- hepatitis
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- 108090000765 processed proteins & peptides Proteins 0.000 title claims description 12
- 239000003112 inhibitor Substances 0.000 title abstract description 42
- 208000005176 Hepatitis C Diseases 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 137
- HYGWNUKOUCZBND-UHFFFAOYSA-N azanide Chemical compound [NH2-] HYGWNUKOUCZBND-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229940124771 HCV-NS3 protease inhibitor Drugs 0.000 claims abstract description 8
- 108700012707 hepatitis C virus NS3 Proteins 0.000 claims abstract 2
- 238000000034 method Methods 0.000 claims description 78
- 239000000203 mixture Substances 0.000 claims description 70
- 241000711549 Hepacivirus C Species 0.000 claims description 66
- 150000003839 salts Chemical class 0.000 claims description 46
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- -1 methoxy, ethoxy, propoxy, 1-methylethoxy, methylthio, ethylthio, propylthio Chemical group 0.000 claims description 40
- 230000008569 process Effects 0.000 claims description 40
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- 238000011282 treatment Methods 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 20
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- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 16
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
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- 229910052763 palladium Inorganic materials 0.000 description 1
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- 230000001717 pathogenic effect Effects 0.000 description 1
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- 229910052700 potassium Inorganic materials 0.000 description 1
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- ZMJJCODMIXQWCQ-UHFFFAOYSA-N potassium;di(propan-2-yl)azanide Chemical compound [K+].CC(C)[N-]C(C)C ZMJJCODMIXQWCQ-UHFFFAOYSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
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- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- PYJBLCPUFFGGKV-UHFFFAOYSA-N tert-butyl 1-sulfamoylcyclopropane-1-carboxylate Chemical compound CC(C)(C)OC(=O)C1(S(N)(=O)=O)CC1 PYJBLCPUFFGGKV-UHFFFAOYSA-N 0.000 description 1
- SOROHDKXLRHTPF-UHFFFAOYSA-N tert-butyl 2-methyl-2-sulfamoylcyclopropane-1-carboxylate Chemical compound CC(C)(C)OC(=O)C1CC1(C)S(N)(=O)=O SOROHDKXLRHTPF-UHFFFAOYSA-N 0.000 description 1
- NBXGDPBFRRQZEV-UHFFFAOYSA-N tert-butyl n-cyclopropylsulfonylcarbamate Chemical compound CC(C)(C)OC(=O)NS(=O)(=O)C1CC1 NBXGDPBFRRQZEV-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
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- XJRBFBKDHIEHJR-UHFFFAOYSA-N thieno[3,2-b]pyridin-2-ol Chemical compound C1=CC=C2SC(O)=CC2=N1 XJRBFBKDHIEHJR-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US70095005P | 2005-07-20 | 2005-07-20 | |
| PCT/CA2006/001160 WO2007009227A1 (en) | 2005-07-20 | 2006-07-17 | Hepatitis c inhibitor peptide analogs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2009501732A true JP2009501732A (ja) | 2009-01-22 |
| JP2009501732A5 JP2009501732A5 (OSRAM) | 2009-09-03 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2008521756A Ceased JP2009501732A (ja) | 2005-07-20 | 2006-07-17 | Ｃ型肝炎インヒビターペプチド類似体 |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US20080200497A1 (OSRAM) |
| EP (1) | EP1910378B1 (OSRAM) |
| JP (1) | JP2009501732A (OSRAM) |
| CA (1) | CA2615921C (OSRAM) |
| WO (1) | WO2007009227A1 (OSRAM) |
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| MY140680A (en) | 2002-05-20 | 2010-01-15 | Bristol Myers Squibb Co | Hepatitis c virus inhibitors |
| US7741281B2 (en) | 2005-11-03 | 2010-06-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2008008776A2 (en) | 2006-07-11 | 2008-01-17 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| BRPI0714343A2 (pt) | 2006-07-13 | 2013-03-19 | Achillion Pharmaceuticals Inc | peptÍdeos de 4-amino-4-oxobutanoil como inibidores de replicaÇço viral |
| US8343477B2 (en) | 2006-11-01 | 2013-01-01 | 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 |
| US7763584B2 (en) | 2006-11-16 | 2010-07-27 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8003604B2 (en) | 2006-11-16 | 2011-08-23 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7888464B2 (en) | 2006-11-16 | 2011-02-15 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| JP2010519339A (ja) | 2007-02-26 | 2010-06-03 | 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 | Ｈｃｖ複製阻害剤として有用な三級アミン置換ペプチド |
| US20090047252A1 (en) * | 2007-06-29 | 2009-02-19 | Gilead Sciences, Inc. | Antiviral compounds |
| WO2009042668A2 (en) | 2007-09-24 | 2009-04-02 | Achillion Pharmaceuticals, Inc. | Urea-containing peptides as inhibitors of viral replication |
| US8383583B2 (en) | 2007-10-26 | 2013-02-26 | Enanta Pharmaceuticals, Inc. | Macrocyclic, pyridazinone-containing hepatitis C serine protease inhibitors |
| MX2010006313A (es) | 2007-12-19 | 2010-06-25 | Boehringer Ingelheim Int | Inhibidores de la polimerasa virica. |
| CN104557861A (zh) | 2007-12-21 | 2015-04-29 | 阿维拉制药公司 | Hcv蛋白酶抑制剂和其用途 |
| US8309685B2 (en) | 2007-12-21 | 2012-11-13 | Celgene Avilomics Research, Inc. | HCV protease inhibitors and uses thereof |
| EP2237666A4 (en) | 2007-12-21 | 2012-05-16 | Avila Therapeutics Inc | HCV PROTEASE INHIBITORS AND USES THEREOF |
| US8202996B2 (en) | 2007-12-21 | 2012-06-19 | Bristol-Myers Squibb Company | Crystalline forms of N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-4-((7-chloro-4-methoxy-1-isoquinolinyl)oxy)-N- ((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)-L-prolinamide |
| US8293705B2 (en) | 2007-12-21 | 2012-10-23 | Avila Therapeutics, Inc. | HCV protease inhibitors and uses thereof |
| CN101977915B (zh) | 2008-02-04 | 2014-08-13 | 埃迪尼克斯医药公司 | 大环丝氨酸蛋白酶抑制剂 |
| CN102015652A (zh) | 2008-03-20 | 2011-04-13 | 益安药业 | 作为丙型肝炎病毒抑制剂的氟化大环化合物 |
| US8163921B2 (en) | 2008-04-16 | 2012-04-24 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US7964560B2 (en) | 2008-05-29 | 2011-06-21 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2009148923A1 (en) | 2008-05-29 | 2009-12-10 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| US8207341B2 (en) | 2008-09-04 | 2012-06-26 | Bristol-Myers Squibb Company | Process or synthesizing substituted isoquinolines |
| UY32099A (es) | 2008-09-11 | 2010-04-30 | Enanta Pharm Inc | Inhibidores macrocíclicos de serina proteasas de hepatitis c |
| US8044087B2 (en) | 2008-09-29 | 2011-10-25 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US8563505B2 (en) | 2008-09-29 | 2013-10-22 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| CN102245599B (zh) | 2008-12-10 | 2014-05-14 | 艾其林医药公司 | 作为病毒复制抑制剂的新的4-氨基-4-氧代丁酰基肽 |
| US8283310B2 (en) | 2008-12-15 | 2012-10-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| JP2012514605A (ja) | 2009-01-07 | 2012-06-28 | サイネクシス，インコーポレーテッド | Ｈｃｖおよびｈｉｖ感染の治療への使用におけるシクロスポリン誘導体 |
| JP2012523419A (ja) | 2009-04-08 | 2012-10-04 | イデニク プハルマセウティカルス，インコーポレイテッド | 大環状セリンプロテアーゼ阻害剤 |
| JP2013501068A (ja) | 2009-08-05 | 2013-01-10 | アイディニックス ファーマシューティカルズ インコーポレイテッド | 大環状セリンプロテアーゼ阻害剤 |
| MX2013007677A (es) | 2010-12-30 | 2013-07-30 | Abbvie Inc | Inhibidores macrociclicos de serina proteasa de hepatitis. |
| US8951964B2 (en) | 2010-12-30 | 2015-02-10 | Abbvie Inc. | Phenanthridine macrocyclic hepatitis C serine protease inhibitors |
| TW201309690A (zh) | 2011-02-10 | 2013-03-01 | Idenix Pharmaceuticals Inc | 巨環絲胺酸蛋白酶抑制劑，其醫藥組合物及其於治療ｈｃｖ感染之用途 |
| US8957203B2 (en) | 2011-05-05 | 2015-02-17 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| US10201584B1 (en) | 2011-05-17 | 2019-02-12 | Abbvie Inc. | Compositions and methods for treating HCV |
| US8691757B2 (en) | 2011-06-15 | 2014-04-08 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| SI2909205T1 (sl) | 2012-10-19 | 2017-02-28 | Bristol-Myers Squibb Company | 9-metil substituiran heksadekahidrociklopropa(e)pirolo(1,2-A)(1,4)diazaciklopentadecinil karbamat derivati kot nestrukturalni 3 (NS3) proteazni inhibitorji za zdravljenje hepatitis C virusnih infekcij |
| US9643999B2 (en) | 2012-11-02 | 2017-05-09 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2014071007A1 (en) | 2012-11-02 | 2014-05-08 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| US9598433B2 (en) | 2012-11-02 | 2017-03-21 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2014070974A1 (en) | 2012-11-05 | 2014-05-08 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| US9580463B2 (en) | 2013-03-07 | 2017-02-28 | Bristol-Myers Squibb Company | Hepatitis C virus inhibitors |
| WO2014152928A2 (en) | 2013-03-14 | 2014-09-25 | Achillion Pharmaceuticals, Inc. | Novel processes for producing sovaprevir |
| US9006423B2 (en) | 2013-03-15 | 2015-04-14 | Achillion Pharmaceuticals Inc. | Process for making a 4-amino-4-oxobutanoyl peptide cyclic analogue, an inhibitor of viral replication, and intermediates thereof |
| BR112015023351A2 (pt) | 2013-03-15 | 2017-07-18 | Achillion Pharmaceuticals Inc | forma cristalina de sovaprevir, composição farmacêutica, e, método para tratar um distúrbio |
| US9085607B2 (en) | 2013-03-15 | 2015-07-21 | Achillion Pharmaceuticals, Inc. | ACH-0142684 sodium salt polymorph, composition including the same, and method of manufacture thereof |
| WO2015103490A1 (en) | 2014-01-03 | 2015-07-09 | Abbvie, Inc. | Solid antiviral dosage forms |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6468350A (en) * | 1987-08-17 | 1989-03-14 | American Cyanamid Co | Herbicide and intermediate |
| WO2003099274A1 (en) * | 2002-05-20 | 2003-12-04 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| WO2003099316A1 (en) * | 2002-05-20 | 2003-12-04 | Bristol-Myers Squibb Company | Heterocyclicsulfonamide hepatitis c virus inhibitors |
| WO2004037855A1 (en) * | 2002-10-25 | 2004-05-06 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis c virus |
| WO2004043339A2 (en) * | 2002-05-20 | 2004-05-27 | Bristol-Myers Squibb Company | Substituted cycloalkyl p1' hepatitis c virus inhibitors |
| WO2005046712A1 (en) * | 2003-11-12 | 2005-05-26 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4883914A (en) * | 1987-08-17 | 1989-11-28 | American Cyanamid Company | Benzenesulfonyl carboxamide compounds useful as herbicidal agents |
| US6323180B1 (en) * | 1998-08-10 | 2001-11-27 | Boehringer Ingelheim (Canada) Ltd | Hepatitis C inhibitor tri-peptides |
| AU2002248147B2 (en) * | 2000-11-20 | 2006-04-06 | Bristol-Myers Squibb Company | Hepatitis C tripeptide inhibitors |
| US6642204B2 (en) * | 2002-02-01 | 2003-11-04 | Boehringer Ingelheim International Gmbh | Hepatitis C inhibitor tri-peptides |
| CA2474156C (en) * | 2002-02-01 | 2011-09-20 | Boehringer Ingelheim International Gmbh | Tripeptides having a hydroxyproline ether of a substituted quinoline for the inhibition of ns3 (hepatitis c) |
| CA2556669C (en) * | 2004-06-28 | 2012-05-01 | Boehringer Ingelheim International Gmbh | Hepatitis c inhibitor peptide analogs |
-
2006
- 2006-07-17 WO PCT/CA2006/001160 patent/WO2007009227A1/en not_active Ceased
- 2006-07-17 EP EP06761122A patent/EP1910378B1/en not_active Not-in-force
- 2006-07-17 JP JP2008521756A patent/JP2009501732A/ja not_active Ceased
- 2006-07-17 CA CA2615921A patent/CA2615921C/en not_active Expired - Fee Related
- 2006-07-17 US US11/996,452 patent/US20080200497A1/en not_active Abandoned
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6468350A (en) * | 1987-08-17 | 1989-03-14 | American Cyanamid Co | Herbicide and intermediate |
| WO2003099274A1 (en) * | 2002-05-20 | 2003-12-04 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
| WO2003099316A1 (en) * | 2002-05-20 | 2003-12-04 | 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 |
| WO2004037855A1 (en) * | 2002-10-25 | 2004-05-06 | Boehringer Ingelheim International Gmbh | Macrocyclic peptides active against the hepatitis c virus |
| WO2005046712A1 (en) * | 2003-11-12 | 2005-05-26 | Bristol-Myers Squibb Company | Hepatitis c virus inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1910378B1 (en) | 2012-06-20 |
| WO2007009227A1 (en) | 2007-01-25 |
| US20080200497A1 (en) | 2008-08-21 |
| EP1910378A4 (en) | 2009-04-29 |
| CA2615921A1 (en) | 2007-01-25 |
| EP1910378A1 (en) | 2008-04-16 |
| CA2615921C (en) | 2011-09-13 |
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