ES2676209T3 - Composiciones de 5-etil-2-{4-[4-(4-tetrazol-1-il-fenoximetil)-tiazol-2-il]-piperidin-1-il}-pirimidina - Google Patents
Composiciones de 5-etil-2-{4-[4-(4-tetrazol-1-il-fenoximetil)-tiazol-2-il]-piperidin-1-il}-pirimidina Download PDFInfo
- Publication number
- ES2676209T3 ES2676209T3 ES11728490.1T ES11728490T ES2676209T3 ES 2676209 T3 ES2676209 T3 ES 2676209T3 ES 11728490 T ES11728490 T ES 11728490T ES 2676209 T3 ES2676209 T3 ES 2676209T3
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- Prior art keywords
- compound
- tetrazol
- weight
- pyrimidine
- ethyl
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- NFTMKHWBOINJGM-UHFFFAOYSA-N 2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-4-[[4-(tetrazol-1-yl)phenoxy]methyl]-1,3-thiazole Chemical group N1=CC(CC)=CN=C1N1CCC(C=2SC=C(COC=3C=CC(=CC=3)N3N=NN=C3)N=2)CC1 NFTMKHWBOINJGM-UHFFFAOYSA-N 0.000 title claims abstract description 56
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Classifications
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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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Landscapes
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- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US35798110P | 2010-06-23 | 2010-06-23 | |
| US357981P | 2010-06-23 | ||
| PCT/US2011/040972 WO2011163090A1 (en) | 2010-06-23 | 2011-06-17 | Compositions of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
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| Publication Number | Publication Date |
|---|---|
| ES2676209T3 true ES2676209T3 (es) | 2018-07-17 |
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| ES11728490.1T Active ES2676209T3 (es) | 2010-06-23 | 2011-06-17 | Composiciones de 5-etil-2-{4-[4-(4-tetrazol-1-il-fenoximetil)-tiazol-2-il]-piperidin-1-il}-pirimidina |
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| Country | Link |
|---|---|
| US (2) | US9241924B2 (enExample) |
| EP (1) | EP2585048B1 (enExample) |
| JP (1) | JP5847813B2 (enExample) |
| CN (2) | CN109674753A (enExample) |
| BR (1) | BR112012032248A2 (enExample) |
| CA (1) | CA2802541A1 (enExample) |
| ES (1) | ES2676209T3 (enExample) |
| WO (1) | WO2011163090A1 (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7638541B2 (en) | 2006-12-28 | 2009-12-29 | Metabolex Inc. | 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
| EP2185544B1 (en) | 2007-07-19 | 2014-11-26 | Cymabay Therapeutics, Inc. | N-azacyclic substituted pyrrole, pyrazole, imidazole, triazole and tetrazole derivatives as agonists of the rup3 or gpr119 for the treatment of diabetes and metabolic disorders |
| CA2719507C (en) * | 2008-03-31 | 2018-03-27 | Metabolex, Inc. | Oxymethylene aryl compounds and uses thereof |
| US20110160222A1 (en) * | 2008-11-26 | 2011-06-30 | Metabolex, Inc. | Modulators of glucose homeostasis for the treatment of diabetes and metabolic disorders |
| EP2483281B1 (en) | 2009-10-01 | 2014-06-04 | Cymabay Therapeutics, Inc. | Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts |
| BR112012032248A2 (pt) | 2010-06-23 | 2016-09-13 | Metabolex Inc | composições de 5-etil-2-{4-[-4(-4-tetrazol-1-il-fenoximetil)-tiazol-2-il]-piperidin-1-il}-pirimidina |
| CA2935307C (en) * | 2013-12-31 | 2023-05-09 | Ascendia Pharmaceuticals, Llc | Pharmaceutical compositions for poorly water-soluble compounds |
| ES2753582T3 (es) * | 2014-06-11 | 2020-04-13 | Bayer Cropscience Ag | Preparación de piperidin-4-carbotioamida |
| WO2018026890A1 (en) * | 2016-08-03 | 2018-02-08 | Cymabay Therapeutics | Oxymethylene aryl compounds for treating inflammatory gastrointestinal diseases or gastrointestinal conditions |
| PH12022552277A1 (en) | 2020-02-28 | 2024-03-04 | Kallyope Inc | Gpr40 agonists |
| CA3178994A1 (en) | 2020-05-19 | 2021-11-25 | Iyassu Sebhat | Ampk activators |
| JP2023531726A (ja) | 2020-06-26 | 2023-07-25 | キャリーオペ,インク. | Ampkアクチベーター |
Family Cites Families (99)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3108117A (en) | 1959-02-12 | 1963-10-22 | Mead Johnson & Co | 3-benzyl-1, 2-diloweralkyl-3-pyrrolidinols |
| US3778443A (en) | 1969-02-13 | 1973-12-11 | Ciba Geigy Ag | 4-tetrahydro pyridyl,hydroxy alkyl pyrazoles |
| US3536809A (en) | 1969-02-17 | 1970-10-27 | Alza Corp | Medication method |
| US3598123A (en) | 1969-04-01 | 1971-08-10 | Alza Corp | Bandage for administering drugs |
| US3845770A (en) | 1972-06-05 | 1974-11-05 | Alza Corp | Osmatic dispensing device for releasing beneficial agent |
| GB1422263A (en) | 1973-01-30 | 1976-01-21 | Ferrosan As | 4-phenyl-piperidine compounds |
| US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
| DE2701705A1 (de) | 1976-01-28 | 1977-08-04 | Sandoz Ag | Neue organische verbindungen, ihre verwendung und herstellung |
| US4008719A (en) | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
| CA1146866A (en) | 1979-07-05 | 1983-05-24 | Yamanouchi Pharmaceutical Co. Ltd. | Process for the production of sustained release pharmaceutical composition of solid medical material |
| DE3438830A1 (de) | 1984-10-23 | 1986-04-30 | Rentschler Arzneimittel | Nifedipin enthaltende darreichungsform und verfahren zu ihrer herstellung |
| US5013556A (en) | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
| JP2527107B2 (ja) * | 1991-04-16 | 1996-08-21 | 日本新薬株式会社 | 固体分散体の製造方法 |
| US5817667A (en) | 1991-04-17 | 1998-10-06 | University Of Georgia Research Foudation | Compounds and methods for the treatment of cancer |
| US5340591A (en) | 1992-01-24 | 1994-08-23 | Fujisawa Pharmaceutical Co., Ltd. | Method of producing a solid dispersion of the sparingly water-soluble drug, nilvadipine |
| JP3265680B2 (ja) | 1992-03-12 | 2002-03-11 | 大正製薬株式会社 | 経口製剤用組成物 |
| AU4444393A (en) | 1992-09-01 | 1994-03-10 | Zeneca Limited | Pyrrolidine derivatives |
| GB9310713D0 (en) | 1993-05-24 | 1993-07-07 | Zeneca Ltd | Aryl substituted heterocycles |
| ATE279406T1 (de) | 1995-01-12 | 2004-10-15 | Glaxo Group Ltd | Piperidinderivate mit tachykinin-antagonistischer wirkung |
| US6048876A (en) | 1995-01-23 | 2000-04-11 | Suntory Limited | Medicament for the alleviation or treatment of symptom derived from ischemic disease and compound useful therefor |
| DE19504832A1 (de) | 1995-02-14 | 1996-08-22 | Basf Ag | Feste Wirkstoff-Zubereitungen |
| KR100384979B1 (ko) | 1995-09-07 | 2003-10-17 | 에프. 호프만-라 로슈 아게 | 심부전증및신부전증치료용의신규한4-(옥시알콕시페닐)-3-옥시-피페리딘 |
| JPH11513382A (ja) | 1995-10-20 | 1999-11-16 | ドクトル カルル トーマエ ゲゼルシャフト ミット ベシュレンクテル ハフツング | 5員複素環化合物、これらの化合物を含む医薬品、それらの使用及びそれらの調製方法 |
| KR100537843B1 (ko) | 1996-07-22 | 2006-04-28 | 다이이치 아스비오파마 가부시키가이샤 | 아릴피페리디놀및아릴피페리딘유도체및이들을함유하는약제 |
| ATE364374T1 (de) * | 1997-08-11 | 2007-07-15 | Pfizer Prod Inc | Feste pharmazeutische dispersionen mit erhöhter bioverfügbarkeit |
| US6274735B1 (en) | 1998-08-10 | 2001-08-14 | Hoffmann-La Roche Inc. | Process and intermediates for preparation of substituted piperidines |
| IT1303737B1 (it) | 1998-11-11 | 2001-02-23 | Smithkline Beecham Spa | Derivati fenilpiperidinici procedimento per la loro preparazione eloro uso come ligandi del recettore orl-1. |
| US20030017528A1 (en) | 1998-11-20 | 2003-01-23 | Ruoping Chen | Human orphan G protein-coupled receptors |
| PT1133559E (pt) | 1998-11-20 | 2005-10-31 | Arena Pharm Inc | Receptor acoplato a proteina g orfao humano, rup3 |
| ES2307482T3 (es) * | 1999-02-10 | 2008-12-01 | Pfizer Products Inc. | Dispersiones farmaceuticas solidas. |
| US6221660B1 (en) | 1999-02-22 | 2001-04-24 | Synaptic Pharmaceutical Corporation | DNA encoding SNORF25 receptor |
| GB9912416D0 (en) | 1999-05-28 | 1999-07-28 | Pfizer Ltd | Compounds useful in therapy |
| GB9923177D0 (en) | 1999-09-30 | 1999-12-01 | Pfizer Ltd | Novel polypeptide |
| IL139073A0 (en) | 1999-10-21 | 2001-11-25 | Pfizer | Treatment of neuropathy |
| EP1176147A1 (en) | 2000-07-28 | 2002-01-30 | Pfizer Limited | Process for the preparation of pyrazolo[4,3-d]pyrimidin-7-ones and intermediates thereof |
| US6770645B2 (en) | 2001-03-16 | 2004-08-03 | Pfizer Inc. | Pharmaceutically active compounds |
| US6784185B2 (en) | 2001-03-16 | 2004-08-31 | Pfizer Inc. | Pharmaceutically active compounds |
| US20030095958A1 (en) | 2001-04-27 | 2003-05-22 | Bhisetti Govinda R. | Inhibitors of bace |
| US20030003157A1 (en) | 2001-06-06 | 2003-01-02 | University Of Medicine & Dentistry Of New Jersey | Collagen compositions and methods for making and using the same |
| WO2003014110A1 (en) | 2001-08-08 | 2003-02-20 | Takeda Chemical Industries, Ltd. | Benzazepine derivative, process for producing the same, and use |
| EP1469830A2 (en) * | 2002-02-01 | 2004-10-27 | Pfizer Products Inc. | Method for making homogeneous spray-dried solid amorphous drug dispersions using pressure nozzles |
| JPWO2003091216A1 (ja) | 2002-04-25 | 2005-09-02 | 住友製薬株式会社 | 新規ピペリジン誘導体 |
| GB0224919D0 (en) | 2002-10-25 | 2002-12-04 | Pfizer Ltd | Triazole compounds useful in therapy |
| GB0230162D0 (en) | 2002-12-24 | 2003-02-05 | Metris Therapeutics Ltd | Compounds useful in inhibiting angiogenesis |
| ES2268341T3 (es) | 2003-03-05 | 2007-03-16 | Maus S.P.A. | Metodo para mecanizar un disco de freno. |
| GB0308333D0 (en) | 2003-04-10 | 2003-05-14 | Glaxo Group Ltd | Novel compounds |
| MXPA05013474A (es) | 2003-06-13 | 2006-03-09 | Schering Ag | Derivados de quinolilamida como antagonistas de ccr-5. |
| US7132426B2 (en) | 2003-07-14 | 2006-11-07 | Arena Pharmaceuticals, Inc. | Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto |
| KR20060036105A (ko) | 2003-07-29 | 2006-04-27 | 제논 파마슈티칼스 인크. | 피리딜 유도체 및 그의 치료제로서의 용도 |
| FR2862647B1 (fr) | 2003-11-25 | 2008-07-04 | Aventis Pharma Sa | Derives de pyrazolyle, procede de preparation et intermediaires de ce procede a titre de medicaments et de compositions pharmaceutiques les renfermant |
| US7235641B2 (en) | 2003-12-22 | 2007-06-26 | Micromet Ag | Bispecific antibodies |
| NZ547965A (en) | 2003-12-24 | 2009-12-24 | Prosidion Ltd | 1,2,4-Oxadiazole derivatives as GPCR receptor agonists |
| TW200538433A (en) | 2004-02-24 | 2005-12-01 | Irm Llc | Immunosuppressant compounds and compositiions |
| AU2005251909A1 (en) | 2004-06-08 | 2005-12-22 | Nsab, Filial Af Neurosearch Sweden Ab, Sverige | New disubstituted phenylpiperidines as modulators of dopamine and serotonin neurotransmission |
| PT1852433E (pt) | 2004-10-29 | 2012-02-08 | Zeria Pharm Co Ltd | Derivados de carbazole, seus solvatos ou seus sais farmaceuticamente aceitáveis |
| TW200633990A (en) | 2004-11-18 | 2006-10-01 | Takeda Pharmaceuticals Co | Amide compound |
| US8211929B2 (en) | 2004-12-30 | 2012-07-03 | Exelixis, Inc. | Pyrimidine derivatives as kinase modulators and method of use |
| GB0428526D0 (en) | 2004-12-30 | 2005-02-09 | Novartis Ag | Organic compounds |
| MY148521A (en) | 2005-01-10 | 2013-04-30 | Arena Pharm Inc | Substituted pyridinyl and pyrimidinyl derivatives as modulators of metabolism and the treatment of disorders related thereto |
| DOP2006000008A (es) | 2005-01-10 | 2006-08-31 | Arena Pharm Inc | Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1 |
| US8277495B2 (en) | 2005-01-13 | 2012-10-02 | Candela Corporation | Method and apparatus for treating a diseased nail |
| AU2006216941B2 (en) | 2005-02-16 | 2009-12-03 | Pharmacopeia, Llc | Heteroaryl substituted pyrazinyl-piperazine-piperidines with CXCR3 antagonist activity |
| EP1888529A2 (en) | 2005-05-18 | 2008-02-20 | Wyeth | 3-cyanoquinoline inhibitors of tpl2 kinase and methods of making and using the same |
| EP1888512A2 (en) | 2005-06-06 | 2008-02-20 | Smithkline Beecham Corporation | Chemical compounds |
| CA2611216A1 (en) | 2005-06-15 | 2006-12-21 | Pfizer Limited | 3-phenylazetidine derivatives as dopamine agonists |
| WO2007023507A2 (en) | 2005-06-20 | 2007-03-01 | Wockhardt Limited | Oxazolidinones bearing antimicrobial activity composition and methods of preparation |
| JP5114395B2 (ja) | 2005-06-30 | 2013-01-09 | プロシディオン・リミテッド | Gpcrアゴニスト |
| JP2008545008A (ja) | 2005-06-30 | 2008-12-11 | プロシディオン・リミテッド | Gpcrアゴニスト |
| ATE429430T1 (de) | 2005-09-16 | 2009-05-15 | Arena Pharm Inc | Stoffwechselmodulatoren und behandlung damit verbundener erkrankungen |
| BRPI0617207A2 (pt) | 2005-09-29 | 2011-07-19 | Sanofi Aventis | derivados de fenil-1,2,4-oxadiazolona, processos para sua preparação e seu uso como produtos farmacêuticos |
| WO2007066189A2 (en) * | 2005-12-09 | 2007-06-14 | Pfizer Products Inc. | Salts, prodrugs and formulations of 1-[5-(4-amino-7-isopropyl-7h-pyrrolo[2,3-d]pyrimidine-5-carbonyl)-2-methoxy-phenyl]-3-(2,4-dichloro-phenyl)-urea |
| PE20071221A1 (es) | 2006-04-11 | 2007-12-14 | Arena Pharm Inc | Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas |
| EP2043744A2 (en) | 2006-07-13 | 2009-04-08 | SmithKline Beecham Corporation | Chemical compounds |
| US8343548B2 (en) * | 2006-08-08 | 2013-01-01 | Shin-Etsu Chemical Co., Ltd. | Solid dosage form comprising solid dispersion |
| US20080103141A1 (en) | 2006-08-30 | 2008-05-01 | Biovitrum | New compounds |
| EP2101741B1 (en) * | 2006-10-17 | 2010-08-11 | Bend Research, Inc. | Solid dispersion comprising a poorly water soluble drug |
| EP2094683B1 (en) | 2006-12-06 | 2011-10-12 | GlaxoSmithKline LLC | Bicyclic compounds and use as antidiabetics |
| US7638541B2 (en) | 2006-12-28 | 2009-12-29 | Metabolex Inc. | 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
| ZA200904281B (en) * | 2006-12-28 | 2010-08-25 | Metabolex Inc | Heterocyclic receptor agonists for the treatment of diabetes and metabolic disorders |
| ES2352880T3 (es) | 2007-03-08 | 2011-02-23 | Irm Llc | Compuestos y composiciones como moduladores de la actividad de gpr119. |
| EP2014656A3 (en) | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | New heteocyclic h3 antagonists |
| JP2010533672A (ja) | 2007-07-19 | 2010-10-28 | エフ.ホフマン−ラ ロシュ アーゲー | 新規ヘテロシクリル化合物およびケモカインアンタゴニストとしてのそれらの使用 |
| EP2185544B1 (en) | 2007-07-19 | 2014-11-26 | Cymabay Therapeutics, Inc. | N-azacyclic substituted pyrrole, pyrazole, imidazole, triazole and tetrazole derivatives as agonists of the rup3 or gpr119 for the treatment of diabetes and metabolic disorders |
| UY31232A1 (es) | 2007-07-19 | 2009-03-02 | Compuestos derivados de dibenzotifenilamino-cromen-4-onas activas sustituidas y sus isomeros y aplicaciones | |
| DK2019104T3 (da) | 2007-07-19 | 2013-12-16 | Sanofi Sa | Cytotoksiske midler, der omfatter nye tomaymycinderivater, og terapeutisk anvendelse deraf |
| CN101801958B (zh) | 2007-07-19 | 2014-01-29 | 默沙东公司 | 作为蛋白质激酶抑制剂的杂环酰胺化合物 |
| FR2918986B1 (fr) | 2007-07-19 | 2009-09-04 | Sanofi Aventis Sa | Derives de 6-cycloamino-3-(pyridazin-4-yl)imidazo[1,2-b]- pyridazine, leur preparation et leur application en therapeutique |
| WO2009070869A1 (en) | 2007-12-04 | 2009-06-11 | Merck Frosst Canada Ltd. | Renin inhibitors |
| CA2719507C (en) * | 2008-03-31 | 2018-03-27 | Metabolex, Inc. | Oxymethylene aryl compounds and uses thereof |
| AU2009271414A1 (en) | 2008-06-20 | 2010-01-21 | Metabolex, Inc. | Aryl GPR119 agonists and uses thereof |
| US8536176B2 (en) | 2008-08-01 | 2013-09-17 | Nippon Chemiphar Co., Ltd. | GPR119 agonist |
| BRPI0919288A2 (pt) * | 2008-09-10 | 2015-12-15 | Boehring Ingelheim Internat Gmbh | teriapia de combinação para tratamento de diabetes e condições relacionadas. |
| WO2010048149A2 (en) | 2008-10-20 | 2010-04-29 | Kalypsys, Inc. | Heterocyclic modulators of gpr119 for treatment of disease |
| US20110160222A1 (en) | 2008-11-26 | 2011-06-30 | Metabolex, Inc. | Modulators of glucose homeostasis for the treatment of diabetes and metabolic disorders |
| CN102596177B (zh) | 2009-07-01 | 2014-05-28 | 阿昂梅迪克斯公司 | 来源于有核哺乳动物细胞的微囊泡及其应用 |
| EP2483281B1 (en) * | 2009-10-01 | 2014-06-04 | Cymabay Therapeutics, Inc. | Substituted tetrazol-1-yl-phenoxymethyl-thiazol-2-yl-piperidinyl-pyrimidine salts |
| WO2011153435A1 (en) | 2010-06-04 | 2011-12-08 | Metabolex, Inc. | Preparation of 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
| BR112012032248A2 (pt) | 2010-06-23 | 2016-09-13 | Metabolex Inc | composições de 5-etil-2-{4-[-4(-4-tetrazol-1-il-fenoximetil)-tiazol-2-il]-piperidin-1-il}-pirimidina |
| US20120184572A1 (en) | 2011-01-13 | 2012-07-19 | Metabolex, Inc. | Aryl gpr119 agonists and uses thereof |
-
2011
- 2011-06-17 BR BR112012032248A patent/BR112012032248A2/pt not_active Application Discontinuation
- 2011-06-17 JP JP2013516636A patent/JP5847813B2/ja not_active Expired - Fee Related
- 2011-06-17 ES ES11728490.1T patent/ES2676209T3/es active Active
- 2011-06-17 CA CA2802541A patent/CA2802541A1/en not_active Abandoned
- 2011-06-17 CN CN201910082228.2A patent/CN109674753A/zh active Pending
- 2011-06-17 WO PCT/US2011/040972 patent/WO2011163090A1/en not_active Ceased
- 2011-06-17 EP EP11728490.1A patent/EP2585048B1/en not_active Not-in-force
- 2011-06-17 CN CN2011800283946A patent/CN103037843A/zh active Pending
- 2011-06-21 US US13/165,651 patent/US9241924B2/en active Active
-
2016
- 2016-01-21 US US15/002,498 patent/US10098843B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN109674753A (zh) | 2019-04-26 |
| CN103037843A (zh) | 2013-04-10 |
| US20110318418A1 (en) | 2011-12-29 |
| BR112012032248A2 (pt) | 2016-09-13 |
| JP2013529637A (ja) | 2013-07-22 |
| US20160213618A1 (en) | 2016-07-28 |
| CA2802541A1 (en) | 2011-12-29 |
| EP2585048B1 (en) | 2018-04-11 |
| US9241924B2 (en) | 2016-01-26 |
| WO2011163090A1 (en) | 2011-12-29 |
| JP5847813B2 (ja) | 2016-01-27 |
| US10098843B2 (en) | 2018-10-16 |
| EP2585048A1 (en) | 2013-05-01 |
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