MX2014004086A - Compuestos de pirrolopirimidina para el tratamiento del cancer. - Google Patents
Compuestos de pirrolopirimidina para el tratamiento del cancer.Info
- Publication number
- MX2014004086A MX2014004086A MX2014004086A MX2014004086A MX2014004086A MX 2014004086 A MX2014004086 A MX 2014004086A MX 2014004086 A MX2014004086 A MX 2014004086A MX 2014004086 A MX2014004086 A MX 2014004086A MX 2014004086 A MX2014004086 A MX 2014004086A
- Authority
- MX
- Mexico
- Prior art keywords
- compound
- alkyl
- further characterized
- cancer
- mmol
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
-
- 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
- C07D487/04—Ortho-condensed systems
-
- 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
- C07D487/12—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 three hetero rings
- C07D487/18—Bridged systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161542392P | 2011-10-03 | 2011-10-03 | |
| US201161547183P | 2011-10-14 | 2011-10-14 | |
| PCT/US2012/058298 WO2013052417A1 (en) | 2011-10-03 | 2012-10-01 | Pyrrolopyrimidine compounds for the treatment of cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| MX2014004086A true MX2014004086A (es) | 2014-09-22 |
Family
ID=48044101
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MX2014004086A MX2014004086A (es) | 2011-10-03 | 2012-10-01 | Compuestos de pirrolopirimidina para el tratamiento del cancer. |
Country Status (13)
| Country | Link |
|---|---|
| US (3) | US9273056B2 (enExample) |
| EP (1) | EP2763988B1 (enExample) |
| JP (2) | JP2014532060A (enExample) |
| KR (1) | KR102063098B1 (enExample) |
| CN (1) | CN103958510B (enExample) |
| AU (1) | AU2012318896B2 (enExample) |
| BR (1) | BR112014007788A2 (enExample) |
| CA (1) | CA2850617A1 (enExample) |
| ES (1) | ES2650630T3 (enExample) |
| IL (1) | IL231835A0 (enExample) |
| MX (1) | MX2014004086A (enExample) |
| RU (1) | RU2631655C2 (enExample) |
| WO (1) | WO2013052417A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2571361A4 (en) | 2010-05-19 | 2013-11-13 | Univ North Carolina | PYRAZOLOPYRIMIDINE COMPOUNDS FOR CANCER TREATMENT |
| BR112014007788A2 (pt) | 2011-10-03 | 2017-04-18 | Univ North Carolina Chapel Hill | compostos de pirrolopirimidina para tratamento do câncer |
| JP2015517574A (ja) | 2012-05-22 | 2015-06-22 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | がん治療のためのピリミジン化合物 |
| WO2014018535A1 (en) | 2012-07-25 | 2014-01-30 | Salk Institute For Biological Studies | Regulating the interaction between tam ligands and lipid membranes with exposed phosphatidylserine |
| WO2014062774A1 (en) | 2012-10-17 | 2014-04-24 | The University Of North Carolina At Chapel Hill | Pyrazolopyrimidine compounds for the treatment of cancer |
| WO2014085225A1 (en) | 2012-11-27 | 2014-06-05 | The University Of North Carolina At Chapel Hill | Pyrimidine compounds for the treatment of cancer |
| US9649309B2 (en) | 2014-04-11 | 2017-05-16 | The University Of North Carolina At Chapel Hill | Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity |
| CN106188060A (zh) * | 2015-04-29 | 2016-12-07 | 厦门大学 | 嘧啶并吡咯类化合物、其制备方法、药用组合物及其应用 |
| US9840503B2 (en) | 2015-05-11 | 2017-12-12 | Incyte Corporation | Heterocyclic compounds and uses thereof |
| WO2017027717A1 (en) * | 2015-08-12 | 2017-02-16 | Incyte Corporation | Bicyclic fused pyrimidine compounds as tam inhibitors |
| WO2017035366A1 (en) | 2015-08-26 | 2017-03-02 | Incyte Corporation | Pyrrolopyrimidine derivatives as tam inhibitors |
| WO2017062797A1 (en) * | 2015-10-07 | 2017-04-13 | The University Of North Carolina At Chapel Hill | The methods for treatment of tumors |
| US10709708B2 (en) | 2016-03-17 | 2020-07-14 | The University Of North Carolina At Chapel Hill | Method of treating cancer with a combination of MER tyrosine kinase inhibitor and an epidermal growth factor receptor (EGFR) inhibitor |
| TWI828027B (zh) | 2016-03-28 | 2024-01-01 | 美商英塞特公司 | 作為tam抑制劑之吡咯并三嗪化合物 |
| CN118359610A (zh) | 2016-09-16 | 2024-07-19 | 生命医药有限责任公司 | Menin-mll相互作用的抑制剂 |
| CN110177553A (zh) * | 2016-11-17 | 2019-08-27 | 北卡罗来纳大学教堂山分校 | 烷基吡咯并嘧啶类似物及其制备和使用方法 |
| US10633387B2 (en) | 2017-09-27 | 2020-04-28 | Incyte Corporation | Salts of TAM inhibitors |
| US11247990B1 (en) | 2017-12-07 | 2022-02-15 | Array Biopharma Inc | Bicyclic fused pyridine compounds as inhibitors of TAM kinases |
| WO2019133629A1 (en) * | 2017-12-28 | 2019-07-04 | Development Center For Biotechnology | Heterocycle compounds as tyro3, axl and mertk (tam) family of receptor tyrosine kinase inhibitors |
| ES3031110T3 (en) | 2018-06-29 | 2025-07-04 | Incyte Corp | Formulations of an axl/mer inhibitor |
| KR102163494B1 (ko) * | 2018-10-26 | 2020-10-08 | 한국과학기술연구원 | 단백질 키나아제 저해제인 헤테로방향족 매크로시클릭 유도체 |
| US12275737B2 (en) | 2019-04-02 | 2025-04-15 | Meryx, Inc. | Polymorphs of a kinase inhibitor, pharmaceutical compositions containing such a compound, preparation methods, and applications |
| PH12022552347A1 (en) | 2020-03-06 | 2024-01-29 | Incyte Corp | Combination therapy comprising axl/mer and pd-1/pd-l1 inhibitors |
| CN112043710A (zh) * | 2020-09-28 | 2020-12-08 | 广州智睿医药科技有限公司 | 一种治疗或预防与lrrk2激酶或异常lrrk2突变激酶活性相关疾病的药物 |
| CN115073469B (zh) * | 2021-03-15 | 2023-12-22 | 药雅科技(上海)有限公司 | 吡咯并嘧啶类化合物作为激酶抑制剂的制备及其应用 |
| WO2025170773A1 (en) * | 2024-01-26 | 2025-08-14 | The University Of North Carolina At Chapel Hill | Tam-family degraders and uses thereof |
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| US5958930A (en) | 1991-04-08 | 1999-09-28 | Duquesne University Of The Holy Ghost | Pyrrolo pyrimidine and furo pyrimidine derivatives |
| AU3176297A (en) * | 1996-06-25 | 1998-01-14 | Novartis Ag | Substituted 7-amino-pyrrolo{3,2-d}pyrimidines and the use thereof |
| US20080248046A1 (en) | 1997-03-17 | 2008-10-09 | Human Genome Sciences, Inc. | Death domain containing receptor 5 |
| TWI238824B (en) * | 2001-05-14 | 2005-09-01 | Novartis Ag | 4-amino-5-phenyl-7-cyclobutyl-pyrrolo[2,3-d]pyrimidine derivatives |
| US7217710B2 (en) | 2001-10-02 | 2007-05-15 | Smithkline Beecham Corporation | Substituted pyrazolopyrimidines |
| DE10239042A1 (de) | 2002-08-21 | 2004-03-04 | Schering Ag | Makrozyclische Pyrimidine, deren Herstellung und Verwendung als Arzneimittel |
| DE602004012559T2 (de) | 2003-05-28 | 2009-04-30 | Universita Degli Studi Di Siena | 4-SUBSTITUIERTE DERIVATE VON PYRAZOLOi3,4-D PYRIMIDIN UND DEREN VERWENDUNGEN |
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| GB0320728D0 (en) | 2003-09-04 | 2003-10-08 | Kilminster Shaun | Test |
| NZ546611A (en) | 2003-09-18 | 2010-02-26 | Conforma Therapeutics Corp | Novel heterocyclic compounds as HSP90-inhibitors |
| JP5520433B2 (ja) | 2004-01-21 | 2014-06-11 | エモリー ユニバーシティー | 病原体感染を処置するためのチロシンキナーゼインヒビターの組成物および使用 |
| WO2005074603A2 (en) | 2004-02-03 | 2005-08-18 | Abbott Laboratories | Aminobenzoxazoles as therapeutic agents |
| PL1713806T3 (pl) | 2004-02-14 | 2013-09-30 | Irm Llc | Związki i kompozycje jako inhibitory kinaz białkowych |
| WO2005095382A1 (ja) | 2004-03-30 | 2005-10-13 | Kyowa Hakko Kogyo Co., Ltd. | 抗腫瘍剤 |
| JP4790703B2 (ja) * | 2004-04-07 | 2011-10-12 | 武田薬品工業株式会社 | 環式化合物 |
| GB0420719D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
| US8575342B2 (en) | 2004-09-30 | 2013-11-05 | Tibotech Pharmaceuticals Ltd. | HIV inhibiting 5-heterocyclyl pyrimidines |
| WO2006042102A2 (en) * | 2004-10-05 | 2006-04-20 | Neurogen Corporation | Pyrrolo-pyridine, pyrrolo-pyrimidine and related heterocyclic compounds |
| EP1710246A1 (en) | 2005-04-08 | 2006-10-11 | Schering Aktiengesellschaft | Sulfoximine-pyrimidine Macrocycles and the salts thereof, a process for making them, and their pharmaceutical use against cancer |
| US20070105874A1 (en) * | 2005-09-23 | 2007-05-10 | Conforma Therapeutics Corporation | Anti-Tumor Methods Using Multi Drug Resistance Independent Synthetic HSP90 Inhibitors |
| US7547782B2 (en) | 2005-09-30 | 2009-06-16 | Bristol-Myers Squibb Company | Met kinase inhibitors |
| CN101321759A (zh) | 2005-10-06 | 2008-12-10 | 先灵公司 | 作为蛋白激酶抑制剂的吡唑并嘧啶化合物 |
| NZ569236A (en) | 2005-12-08 | 2012-06-29 | Medarex Inc | Human monoclonal antibodies to protein tyrosine kinase 7 (PTK7) and their use |
| US20080299113A1 (en) | 2005-12-19 | 2008-12-04 | Arnold Lee D | Combined treatment with and composition of 6,6-bicyclic ring substituted heterobicyclic protein kinase inhibitor and anti-cancer agents |
| EP1803723A1 (de) | 2006-01-03 | 2007-07-04 | Bayer Schering Pharma Aktiengesellschaft | (2,4,9-triaza-1(2,4)-pyrimidina-3(1,3)-benzenacyclononaphan-3^4-yl)-sulfoximid derivate als selektive inhibitoren der aurora kinase zur behandlung von krebs |
| AU2007233737B2 (en) | 2006-03-30 | 2012-11-29 | Janssen Sciences Ireland Uc | HIV inhibiting 5-amido substituted pyrimidines |
| WO2007125405A2 (en) | 2006-05-01 | 2007-11-08 | Pfizer Products Inc. | Substituted 2-amino-fused heterocyclic compounds |
| GB0610242D0 (en) | 2006-05-23 | 2006-07-05 | Novartis Ag | Organic compounds |
| TWI398252B (zh) | 2006-05-26 | 2013-06-11 | 諾華公司 | 吡咯并嘧啶化合物及其用途 |
| WO2009032703A1 (en) | 2007-08-28 | 2009-03-12 | Irm Llc | 2- (het) arylamino-6-aminopyridine derivatives and fused forms thereof as anaplastic lymphoma kinase inhibitors |
| AU2008309517B2 (en) | 2007-10-12 | 2013-03-14 | Astrazeneca Ab | Inhibitors of protein kinases |
| CA2703519C (en) | 2007-11-09 | 2017-04-18 | The Salk Institute For Biological Studies | Use of tam receptor inhibitors as immunoenhancers and tam activators as immunosuppressors |
| US8338439B2 (en) | 2008-06-27 | 2012-12-25 | Celgene Avilomics Research, Inc. | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
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| WO2010014755A1 (en) | 2008-07-29 | 2010-02-04 | The Regents Of The University Of Colorado | Methods and compounds for enhancing anti-cancer therapy |
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| GB0819105D0 (en) * | 2008-10-17 | 2008-11-26 | Chroma Therapeutics Ltd | Pyrrolo-pyrimidine compounds |
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| US8765727B2 (en) | 2009-01-23 | 2014-07-01 | Incyte Corporation | Macrocyclic compounds and their use as kinase inhibitors |
| TW201102391A (en) * | 2009-03-31 | 2011-01-16 | Biogen Idec Inc | Certain substituted pyrimidines, pharmaceutical compositions thereof, and methods for their use |
| UA107791C2 (en) | 2009-05-05 | 2015-02-25 | Dow Agrosciences Llc | Pesticidal compositions |
| WO2010129802A1 (en) | 2009-05-06 | 2010-11-11 | Portola Pharmaceuticals, Inc. | Inhibitors of jak |
| EP2464661B1 (en) | 2009-08-13 | 2018-01-17 | The Johns Hopkins University | Methods of modulating immune function with anti-b7-h7cr antibodies |
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| WO2011065800A2 (ko) | 2009-11-30 | 2011-06-03 | 주식회사 오스코텍 | 피리미딘 유도체, 이의 제조방법 및 이를 함유하는 약학적 조성물 |
| US9433621B2 (en) | 2010-02-18 | 2016-09-06 | Merck Sharp & Dohme Corp. | Substituted pyridine and pyrimidine derivatives and their use in treating viral infections |
| GB201004311D0 (en) | 2010-03-15 | 2010-04-28 | Proximagen Ltd | New enzyme inhibitor compounds |
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| EP2571361A4 (en) | 2010-05-19 | 2013-11-13 | Univ North Carolina | PYRAZOLOPYRIMIDINE COMPOUNDS FOR CANCER TREATMENT |
| WO2011153553A2 (en) | 2010-06-04 | 2011-12-08 | The Regents Of The University Of California | Methods and compositions for kinase inhibition |
| JP2014005206A (ja) | 2010-10-22 | 2014-01-16 | Astellas Pharma Inc | アリールアミノヘテロ環カルボキサミド化合物 |
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| US8362023B2 (en) | 2011-01-19 | 2013-01-29 | Hoffmann-La Roche Inc. | Pyrazolo pyrimidines |
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| PE20141371A1 (es) | 2011-08-29 | 2014-10-13 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y usos de los mismos |
| MD20140023A2 (ro) * | 2011-09-22 | 2014-06-30 | Pfizer Inc. | Derivaţi de pirolpirimidină şi purină |
| BR112014007788A2 (pt) | 2011-10-03 | 2017-04-18 | Univ North Carolina Chapel Hill | compostos de pirrolopirimidina para tratamento do câncer |
| BR112014021065A8 (pt) | 2012-02-21 | 2018-04-24 | Centre Nat Rech Scient | receptores tam como cofatores de entrada do vírus |
| CN104662018B (zh) | 2012-04-20 | 2017-10-24 | 阿迪维纳斯治疗有限公司 | 取代的杂双环化合物、组合物及其医疗应用 |
| JP2015517574A (ja) | 2012-05-22 | 2015-06-22 | ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル | がん治療のためのピリミジン化合物 |
| WO2014062774A1 (en) | 2012-10-17 | 2014-04-24 | The University Of North Carolina At Chapel Hill | Pyrazolopyrimidine compounds for the treatment of cancer |
| WO2014085225A1 (en) | 2012-11-27 | 2014-06-05 | The University Of North Carolina At Chapel Hill | Pyrimidine compounds for the treatment of cancer |
| WO2015153978A1 (en) | 2014-04-04 | 2015-10-08 | The University Of North Carolina At Chapel Hill | Methods for the treatment of tumors |
| US9649309B2 (en) | 2014-04-11 | 2017-05-16 | The University Of North Carolina At Chapel Hill | Therapeutic uses of selected pyrimidine compounds with anti-Mer tyrosine kinase activity |
-
2012
- 2012-10-01 BR BR112014007788A patent/BR112014007788A2/pt not_active IP Right Cessation
- 2012-10-01 WO PCT/US2012/058298 patent/WO2013052417A1/en not_active Ceased
- 2012-10-01 CA CA2850617A patent/CA2850617A1/en not_active Abandoned
- 2012-10-01 ES ES12839069.7T patent/ES2650630T3/es active Active
- 2012-10-01 CN CN201280056825.4A patent/CN103958510B/zh active Active
- 2012-10-01 EP EP12839069.7A patent/EP2763988B1/en active Active
- 2012-10-01 US US14/348,805 patent/US9273056B2/en active Active
- 2012-10-01 JP JP2014534626A patent/JP2014532060A/ja active Pending
- 2012-10-01 RU RU2014115847A patent/RU2631655C2/ru active
- 2012-10-01 KR KR1020147010156A patent/KR102063098B1/ko active Active
- 2012-10-01 MX MX2014004086A patent/MX2014004086A/es unknown
- 2012-10-01 AU AU2012318896A patent/AU2012318896B2/en active Active
-
2014
- 2014-03-31 IL IL231835A patent/IL231835A0/en unknown
-
2016
- 2016-02-03 US US15/014,573 patent/US9795606B2/en active Active
- 2016-12-28 JP JP2016255095A patent/JP6316925B2/ja active Active
-
2017
- 2017-10-23 US US15/790,700 patent/US10179133B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US9273056B2 (en) | 2016-03-01 |
| US20140243315A1 (en) | 2014-08-28 |
| US10179133B2 (en) | 2019-01-15 |
| AU2012318896A1 (en) | 2014-05-22 |
| CN103958510A (zh) | 2014-07-30 |
| US20160151372A1 (en) | 2016-06-02 |
| RU2631655C2 (ru) | 2017-09-26 |
| ES2650630T3 (es) | 2018-01-19 |
| US9795606B2 (en) | 2017-10-24 |
| CN103958510B (zh) | 2016-10-19 |
| JP2014532060A (ja) | 2014-12-04 |
| JP2017101043A (ja) | 2017-06-08 |
| KR20140095471A (ko) | 2014-08-01 |
| CA2850617A1 (en) | 2013-04-11 |
| BR112014007788A2 (pt) | 2017-04-18 |
| EP2763988A1 (en) | 2014-08-13 |
| EP2763988A4 (en) | 2015-06-03 |
| HK1201256A1 (en) | 2015-08-28 |
| JP6316925B2 (ja) | 2018-04-25 |
| RU2014115847A (ru) | 2015-11-10 |
| KR102063098B1 (ko) | 2020-01-08 |
| US20180104247A1 (en) | 2018-04-19 |
| AU2012318896B2 (en) | 2017-03-02 |
| EP2763988B1 (en) | 2017-09-20 |
| IL231835A0 (en) | 2014-05-28 |
| WO2013052417A1 (en) | 2013-04-11 |
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