DK2739628T3 - Hidtil ukendte makrocyklusser som faktor xia-hæmmere - Google Patents
Hidtil ukendte makrocyklusser som faktor xia-hæmmere Download PDFInfo
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- DK2739628T3 DK2739628T3 DK12762427.8T DK12762427T DK2739628T3 DK 2739628 T3 DK2739628 T3 DK 2739628T3 DK 12762427 T DK12762427 T DK 12762427T DK 2739628 T3 DK2739628 T3 DK 2739628T3
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- C—CHEMISTRY; METALLURGY
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- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/06—Peri-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/06—Peri-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/06—Peri-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/08—Bridged systems
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Claims (13)
- HIDTIL UKENDTE MAKROCYKLUSSER SOM FAKTOR XIA-HÆMMERE PATENTKRAV1. Forbindelse med formlen (I):eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt, et solvat deraf, hvor: ring A er udvalgt fra aryl og en 5- til 6-leddet heterocyklus, der omfatter carbonatomer og 1-4 heteroatomer, der er udvalgt fra N, NH, N(Cu alkyl), S(0)p og O, hvor arylen og heterocyklussen eventuelt er substitueret med R1; ring B er en 5- til 6-leddet heterocyklus, der omfatter: carbonatomer og 1-4 heteroatomer, der er udvalgt fra N, NH, S(0)p og O, hvor heterocyklussen eventuelt er substitueret med R10; ring C er en 4- til 5-leddet heterocyklus, der omfatter: carbonatomer og 1-4 heteroatomer, der er udvalgt fra N, NR9, S(0)p og O, hvor heterocyklussen eventuelt er substitueret med R2; X1 er udvalgt fra Ci.4-alkylen og C2.4-alkenylen; eventuelt ét eller flere af carbonatomerne af alkylenen og alkenylenen kan være erstattet med O, S(0)p, NH og NfC^-alkyl); R1 uafhængigt ved hver forekomst er udvalgt fra H, halogen, N02, C^g-alkyl, OH, OMe og CN; R2 er udvalgt fra H, =0, OH, NH2, CF3, halogen og Ci.4-alkyl eventuelt er substitueret med OH; R3 er udvalgt fra II og Ci_4 alkyl; R2 og R3 alternativt sammen med de atomer, hvortil de er direkte eller indirekte er bundet, danner en ring, hvor ringen eventuelt er substitueret med =0; R4 er udvalgt fra H, Ci_4-alkyl, hydroxyl og C3.6-cycloalkyl; R5 er udvalgt fra II og C^-alkyl; R6 er udvalgt fra H, halogen, C(0)0H og C(0)0(Ci.4-alkyl); R7 er udvalgt fra H, C^-alkyl og CF3; R6 og R7 alternativt sammen er =0; R8 uafhængigt ved hver forekomst er udvalgt fra H, halogen, NHC^O-C^-alkyl, CN, OH, O-Q-4-alkyl; CF3, C02H, C02(Ci.4-alkyl), -CH2C02H, -(CH2)2C02H, -CH2C02(Ci.4-alkyl), -(CH^CO^C^-alkyl), NH2, -CH2NH2, -NHCO(CU4-alkyl), -NHC02(CH2)1.20(C1.4-alkyl), -NHC02(CH2)i_30(C14-alkyl), NHC02CH2CH(C1.4-alkyl)0(C1.4-alkyl), -NHC02(CH2)i_20H, -NHC02CH2C02H, -CH2NHC02(Ci_4-alkyl), -NHClOjNHCC^-alkyl), -NHC(0)N(Ci_4-alkyl)2, NHC(0)NH(Ci.4-alkyl)N[5- til 6-lcddct hctcrocyklus)], -NHS02(CM alkyl), -CONH2, -CONH(Cw alkyl), -CON(C[ ^-alky 1)2 og -CH2CONH2; R9 er udvalgt fra H og C^-alkyl; R10 uafhængigt ved hver forekomst er udvalgt fra H, halogen, CN, =(), OH, NH2, C3.6.cycloalkyl, (',,4-alkoxy, CF3, CH2OH, C02H, CO,(C,^alkyl) og CONH; og p uafhængigt ved hver forekomst er udvalgt fra 0, 1 og 2; forudsat, at følgende forbindelser er udelukket
- 2. Forbindelse ifølge krav 1 med formlen (II):eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt, et solvat deraf, hvor: ring A er udvalgt fra aryl og en 6-leddet heterocyklus, der omfatter: carbonatomer og 1-3 heteroatomer, der er udvalgt fra N, NH og Ν((’μ4 alkyl); ring B er udvalgt fra imidazol, pyridin, pyridon og pyridazin; X1 er udvalgt fra CH2 og CH=CH; W og Q hver uafhængigt er udvalgt fra N, NR9, CRA og GHR2; og R2a er udvalgt fra H, NH2 og C1.4-alkyl.
- 3. Forbindelse ifølge krav 2, eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt, et solvat deraf, hvor: ring A er udvalgt fra phenyl og piperidin;R10 er udvalgt fra H, halogen og CN.
- 4. Forbindelse ifølge krav 3 med formlen (III):eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt, et solvat deraf, hvor:W og Q hver uafhængigt er udvalgt fra N og CR2; Rla og Rlb hver uafhængigt er udvalgt fra H og halogen; R2 uafhængigt ved hver forekomst er udvalgt fra H og C^-alkyl eventuelt substitueret med OH; R2a er udvalgt fra H, NH2 og Me; R4 er udvalgt fra H og Ci_4-alkyl; R5 er udvalgt fra II og Ci_4-alkyl; R6 uafhængigt er udvalgt fra H. C(0)0H og C(0)0(C1.4-alkyl); R7 er udvalgt fra H, C^-alkyl og CF3; R6 og R7 alternativt sammen er =0; og R10 er udvalgt fra H, halogen og CN.
- 5. Forbindelse ifølge krav 4 med formlen (IV):eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt, et solvat deraf, hvor: W og Q hver uafhængigt er udvalgt fra N og CH; Rla og Rlb hver uafhængigt er udvalgt fra H, F og Cl; R4 er udvalgt fra H, methyl, ethyl, propyl, isopropyl og butyl; R5 er Η; R8 er NHC(0)0-CM-alkyl; og R10 er udvalgt fra F1 og CN.
- 6. Forbindelse ifølge krav 5 med formlen (V):eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt, et solvat deraf, hvor: Rla er udvalgt fra H og F; Rlb er Cl; og R4 er udvalgt fra H, methyl, ethyl og isopropyl.
- 7. Forbindelse ifølge krav 4 med formlen (VI):eller en stereoisomer, en tautomer, et farmaceutisk acceptabelt salt, et solvat deraf, hvor:W er udvalgt fra N og CH; Q er udvalgt fra N og CH; Rla og Rlb hver uafhængigt er udvalgt fra F og Cl; R4 er udvalgt fra H, methyl og ethyl; og R8 er NHC(0)0Me.
- 8. Forbindelse ifølge krav 1, udvalgt fra gruppen bestående af:
- 9. Farmaceutisk sammensætning, der omfatter én eller mere forbindelser ifølge et hvilket som helst af kravene 1-8 og en farmaceutisk acceptabel bærer eller fortynder.
- 10. Forbindelse ifølge et hvilket som helst af kravene 1-8, eller en stereoisomer, en tautomer, eller et farmaceutisk acceptabelt salt deraf til anvendelse i terapi.
- 11. Terapeutisk effektiv mængde af en forbindelse ifølge et hvilket som helst af kravene 1-8, eller en stereoisomer, en tautomer, eller et farmaceutisk acceptabelt salt deraf til anvendelse i behandling og/eller profylakse af en tromboembolisk forstyrrelse.
- 12. Terapeutisk effektiv mængde af en forbindelse ifølge et hvilket som helst af kravene 1-8, eller en stereoisomer, en tautomer, eller et farmaceutisk acceptabelt salt deraf, til anvendelse ifølge krav 11, hvor den tromboemboliske forstyrrelse er udvalgt fra gruppen bestående af arterielle kardiovaskulære tromboemboliske forstyrrelser, venøse kardiovaskulære tromboemboliske forstyrrelser og tromboemboliske forstyrrelser i hjertekamrene eller i det perifere kredsløb.
- 13. Terapeutisk effektiv mængde af en forbindelse ifølge et hvilket som helst af kravene 1-8, eller en stereoisomer, en tautomer, eller et farmaceutisk acceptabelt salt deraf, til anvendelse ifølge krav 12, hvor den tromboemboliske forstyrrelse er udvalgt fra ustabil angina, et akut koronart syndrom, atrieflimren, myokardieinfarkt, transient iskæmisk attack, apopleksi, atherosklerose, perifer okklusiv arteriesygdom, venetrombose, dyb venetrombose, thrombophlebitis, arterieemboli, koronaer arterietrombose, cerebral arterietrombose, cerebral emboli, nyreemboli, lungeemboli og trombose som følge af medicinske implantater, anordninger eller procedurer, hvor blod eksponeres for en kunstig overflade, der fremmer trombose.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161515401P | 2011-08-05 | 2011-08-05 | |
PCT/US2012/049706 WO2013022818A1 (en) | 2011-08-05 | 2012-08-06 | Novel macrocycles as factor xia inhibitors |
Publications (1)
Publication Number | Publication Date |
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DK2739628T3 true DK2739628T3 (da) | 2017-09-11 |
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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DK12762427.8T DK2739628T3 (da) | 2011-08-05 | 2012-08-06 | Hidtil ukendte makrocyklusser som faktor xia-hæmmere |
Country Status (21)
Country | Link |
---|---|
US (4) | US9221818B2 (da) |
EP (1) | EP2739628B1 (da) |
JP (1) | JP6158181B2 (da) |
CN (1) | CN103857681B (da) |
AR (1) | AR088748A1 (da) |
BR (1) | BR112014002202A2 (da) |
CA (1) | CA2844254A1 (da) |
CY (1) | CY1119281T1 (da) |
DK (1) | DK2739628T3 (da) |
EA (1) | EA024791B1 (da) |
ES (1) | ES2635088T3 (da) |
HR (1) | HRP20171122T1 (da) |
HU (1) | HUE034487T2 (da) |
LT (1) | LT2739628T (da) |
MX (1) | MX345763B (da) |
PL (1) | PL2739628T3 (da) |
PT (1) | PT2739628T (da) |
RS (1) | RS56244B1 (da) |
SI (1) | SI2739628T1 (da) |
TW (1) | TW201311689A (da) |
WO (1) | WO2013022818A1 (da) |
Families Citing this family (47)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2011100401A1 (en) | 2010-02-11 | 2011-08-18 | Bristol-Myers Squibb Company | Macrocycles as factor xia inhibitors |
TW201319068A (zh) | 2011-08-05 | 2013-05-16 | 必治妥美雅史谷比公司 | 作為xia因子抑制劑之環狀p1接合劑 |
TW201311689A (zh) | 2011-08-05 | 2013-03-16 | 必治妥美雅史谷比公司 | 作為因子xia抑制劑之新穎巨環化合物 |
CN103987697B (zh) | 2011-10-14 | 2017-04-26 | 百时美施贵宝公司 | 作为因子xia抑制剂的取代的四氢异喹啉化合物 |
SI2766346T1 (sl) | 2011-10-14 | 2017-05-31 | Bristol-Myers Squibb Company | Substituirane tetrahidroizokinolinske spojine kot faktor xia inhibitorji |
US9079929B2 (en) | 2011-10-14 | 2015-07-14 | Bristol-Myers Squibb Company | Substituted tetrahydroisoquinoline compounds as factor XIa inhibitors |
PT2882734T (pt) * | 2012-08-03 | 2016-12-09 | Bristol Myers Squibb Co | Di-hidropiridona pi como inibidores do fator xia |
SG11201500271UA (en) * | 2012-08-03 | 2015-03-30 | Bristol Myers Squibb Co | Dihydropyridone p1 as factor xia inhibitors |
TR201807316T4 (tr) | 2012-10-12 | 2018-06-21 | Squibb Bristol Myers Co | Bir faktör XIa inhibitörünün kristalli formları. |
WO2014059202A1 (en) | 2012-10-12 | 2014-04-17 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
US9403774B2 (en) | 2012-10-12 | 2016-08-02 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
US9738655B2 (en) | 2013-03-25 | 2017-08-22 | Bristol-Myers Squibb Company | Tetrahydroisoquinolines containing substituted azoles as factor XIa inhibitors |
WO2014160592A2 (en) | 2013-03-27 | 2014-10-02 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
FR3010076B1 (fr) * | 2013-09-02 | 2016-12-23 | Centre Nat De La Rech Scient - Cnrs - | Inhibiteurs de metalloproteases, leurs procedes de preparation et leurs utilisations therapeutiques |
NO2760821T3 (da) | 2014-01-31 | 2018-03-10 | ||
TWI688564B (zh) * | 2014-01-31 | 2020-03-21 | 美商必治妥美雅史谷比公司 | 作為凝血因子xia抑制劑之具有雜環p2'基團之巨環化合物 |
WO2015123091A1 (en) | 2014-02-11 | 2015-08-20 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
WO2015123093A1 (en) | 2014-02-11 | 2015-08-20 | Merck Sharp & Dohme Corp. | Factor xia inhibitors |
EP3134408B1 (en) | 2014-04-22 | 2020-08-12 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
EP3180317B1 (en) | 2014-07-28 | 2021-04-14 | Merck Sharp & Dohme Corp. | FACTOR XIa INHIBITORS |
ES2714283T3 (es) * | 2014-09-04 | 2019-05-28 | Bristol Myers Squibb Co | Macrociclos de diamida que son inhibidores de FXIa |
NO2721243T3 (da) * | 2014-10-01 | 2018-10-20 | ||
US9453018B2 (en) | 2014-10-01 | 2016-09-27 | Bristol-Myers Squibb Company | Pyrimidinones as factor XIa inhibitors |
WO2016205482A1 (en) | 2015-06-19 | 2016-12-22 | Bristol-Myers Squibb Company | Diamide macrocycles as factor xia inhibitors |
EP3328852B1 (en) | 2015-07-29 | 2021-04-28 | Bristol-Myers Squibb Company | Factor xia macrocyclic inhibitors bearing a non-aromatic p2' group |
JP6629958B2 (ja) | 2015-07-29 | 2020-01-15 | ブリストル−マイヤーズ スクイブ カンパニーBristol−Myers Squibb Company | アルキルまたはシクロアルキルP2’基を担持する大員環の第XIa因子阻害剤 |
RS62807B1 (sr) | 2015-10-01 | 2022-02-28 | Biocryst Pharm Inc | Inhibitori humanog kalikreina plazme |
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2012
- 2012-08-03 TW TW101128173A patent/TW201311689A/zh unknown
- 2012-08-06 RS RS20170852A patent/RS56244B1/sr unknown
- 2012-08-06 PL PL12762427T patent/PL2739628T3/pl unknown
- 2012-08-06 BR BR112014002202A patent/BR112014002202A2/pt not_active Application Discontinuation
- 2012-08-06 SI SI201231004T patent/SI2739628T1/sl unknown
- 2012-08-06 WO PCT/US2012/049706 patent/WO2013022818A1/en active Application Filing
- 2012-08-06 PT PT127624278T patent/PT2739628T/pt unknown
- 2012-08-06 EA EA201490418A patent/EA024791B1/ru not_active IP Right Cessation
- 2012-08-06 CA CA2844254A patent/CA2844254A1/en not_active Abandoned
- 2012-08-06 LT LTEP12762427.8T patent/LT2739628T/lt unknown
- 2012-08-06 ES ES12762427.8T patent/ES2635088T3/es active Active
- 2012-08-06 JP JP2014524152A patent/JP6158181B2/ja active Active
- 2012-08-06 US US14/236,973 patent/US9221818B2/en active Active
- 2012-08-06 HU HUE12762427A patent/HUE034487T2/en unknown
- 2012-08-06 CN CN201280049108.9A patent/CN103857681B/zh active Active
- 2012-08-06 DK DK12762427.8T patent/DK2739628T3/da active
- 2012-08-06 EP EP12762427.8A patent/EP2739628B1/en active Active
- 2012-08-06 MX MX2014000831A patent/MX345763B/es active IP Right Grant
- 2012-08-07 AR ARP120102878A patent/AR088748A1/es unknown
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- 2015-11-16 US US14/942,013 patent/US9611274B2/en active Active
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- 2017-02-21 US US15/437,605 patent/US9902742B2/en active Active
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Also Published As
Publication number | Publication date |
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LT2739628T (lt) | 2017-08-25 |
US20160068544A1 (en) | 2016-03-10 |
AR088748A1 (es) | 2014-07-02 |
US9902742B2 (en) | 2018-02-27 |
CY1119281T1 (el) | 2018-02-14 |
EP2739628A1 (en) | 2014-06-11 |
US10208068B2 (en) | 2019-02-19 |
CA2844254A1 (en) | 2013-02-14 |
US9221818B2 (en) | 2015-12-29 |
JP2014521701A (ja) | 2014-08-28 |
EA024791B1 (ru) | 2016-10-31 |
MX2014000831A (es) | 2014-02-27 |
RS56244B1 (sr) | 2017-11-30 |
PL2739628T3 (pl) | 2017-11-30 |
PT2739628T (pt) | 2017-08-02 |
CN103857681A (zh) | 2014-06-11 |
MX345763B (es) | 2017-02-15 |
EA201490418A1 (ru) | 2014-05-30 |
US20170158712A1 (en) | 2017-06-08 |
TW201311689A (zh) | 2013-03-16 |
SI2739628T1 (sl) | 2017-08-31 |
HRP20171122T1 (hr) | 2017-10-06 |
BR112014002202A2 (pt) | 2017-03-07 |
HUE034487T2 (en) | 2018-02-28 |
US20180148461A1 (en) | 2018-05-31 |
CN103857681B (zh) | 2017-07-14 |
WO2013022818A1 (en) | 2013-02-14 |
JP6158181B2 (ja) | 2017-07-05 |
US9611274B2 (en) | 2017-04-04 |
EP2739628B1 (en) | 2017-06-07 |
ES2635088T3 (es) | 2017-10-02 |
US20140221338A1 (en) | 2014-08-07 |
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