EA031183B1 - Способы улучшения функции диафрагмы - Google Patents
Способы улучшения функции диафрагмы Download PDFInfo
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- EA031183B1 EA031183B1 EA201491605A EA201491605A EA031183B1 EA 031183 B1 EA031183 B1 EA 031183B1 EA 201491605 A EA201491605 A EA 201491605A EA 201491605 A EA201491605 A EA 201491605A EA 031183 B1 EA031183 B1 EA 031183B1
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- Eurasian Patent Office
- Prior art keywords
- diaphragm
- compound
- patient
- skeletal muscle
- muscle
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- 229940117013 triethanolamine oleate Drugs 0.000 description 1
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Classifications
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- 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
- A61K31/52—Purines, e.g. adenine
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- A—HUMAN NECESSITIES
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- 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
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
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- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/02—Antidotes
-
- 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
- A61P7/10—Antioedematous agents; Diuretics
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Neurology (AREA)
- Pulmonology (AREA)
- Physical Education & Sports Medicine (AREA)
- Hospice & Palliative Care (AREA)
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- Neurosurgery (AREA)
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- Cardiology (AREA)
- Toxicology (AREA)
- Hematology (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
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| US201261619261P | 2012-04-02 | 2012-04-02 | |
| PCT/US2013/034824 WO2013151938A1 (en) | 2012-04-02 | 2013-04-01 | Methods for improving diaphragm function |
Publications (2)
| Publication Number | Publication Date |
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| EA201491605A1 EA201491605A1 (ru) | 2015-03-31 |
| EA031183B1 true EA031183B1 (ru) | 2018-11-30 |
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| Application Number | Title | Priority Date | Filing Date |
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| EA201491605A EA031183B1 (ru) | 2012-04-02 | 2013-04-01 | Способы улучшения функции диафрагмы |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US20150065525A1 (https=) |
| EP (1) | EP2834269A4 (https=) |
| JP (3) | JP6345645B2 (https=) |
| KR (1) | KR20160046693A (https=) |
| CN (2) | CN104379597A (https=) |
| AU (2) | AU2013243671B2 (https=) |
| BR (1) | BR112014024552A2 (https=) |
| CA (1) | CA2868507A1 (https=) |
| EA (1) | EA031183B1 (https=) |
| HK (1) | HK1206364A1 (https=) |
| IL (2) | IL234885A0 (https=) |
| MX (1) | MX354965B (https=) |
| PH (1) | PH12014502217A1 (https=) |
| SG (2) | SG10201701101YA (https=) |
| WO (1) | WO2013151938A1 (https=) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US8299248B2 (en) | 2006-08-02 | 2012-10-30 | Cytokinetics, Incorporated | Certain 1H-imidazo[4,5-b]pyrazin-2(3H)-ones and 1H-imidazo[4,5-b]pyrazin-2-ols and methods for their use |
| AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| US9133123B2 (en) | 2010-04-23 | 2015-09-15 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
| AR081626A1 (es) | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
| WO2012178125A1 (en) | 2011-06-22 | 2012-12-27 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| KR101951220B1 (ko) | 2011-07-13 | 2019-02-22 | 싸이토키네틱스, 인코포레이티드 | 조합 als 치료법 |
| CN111840294A (zh) * | 2012-04-11 | 2020-10-30 | 赛特凯恩蒂克公司 | 改善对骨骼肌疲劳的抵抗力的方法 |
| SI2941432T1 (en) | 2012-12-07 | 2018-07-31 | Vertex Pharmaceuticals Incorporated | 2-AMINO-6-FLUORO-N- (5-FLUORO-4- (4- (4- (OXETHAN-3-YL) PIPERAZIN-1-CARBONYL) PIPERIDIN-1-YLIPRIDIN-3-YL) 1,5 ALFA) PYRIMIDINE-3-CARBOXAMIDE AS ATR KINAZE INHIBITOR |
| EP2970240B1 (en) | 2013-03-14 | 2018-01-10 | Novartis AG | 3-pyrimidin-4-yl-oxazolidin-2-ones as inhibitors of mutant idh |
| JP2016512815A (ja) | 2013-03-15 | 2016-05-09 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ａｔｒキナーゼの阻害剤として有用な縮合ピラゾロピリミジン誘導体 |
| WO2014143242A1 (en) | 2013-03-15 | 2014-09-18 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of atr kinase |
| EP2970289A1 (en) | 2013-03-15 | 2016-01-20 | Vertex Pharmaceuticals Inc. | Compounds useful as inhibitors of atr kinase |
| DK3077397T3 (da) | 2013-12-06 | 2019-12-16 | Vertex Pharma | 2-amino-6-fluor-n-[5-fluor-pyridin-3-yl]pyrazolo[1,5-a]pyrimidin-3-carboxamidforbindelse anvendelig som atr-kinase-inhibitor, dens fremstilling, forskellige faste former og radiomarkerede derivater deraf |
| HUE057533T2 (hu) | 2014-04-29 | 2022-05-28 | Cytokinetics Inc | Eljárások vitálkapacitás csökkenésének gátlására |
| PL3152212T3 (pl) | 2014-06-05 | 2020-06-15 | Vertex Pharmaceuticals Inc. | Radioznakowane pochodne związku 2-amino-6-fluoro-n-[5-fluoro-piridyn-3-ylo]-pirazolo[1,5-a]pirymidino-3-karboksamidu przydatne jako inhibitor kinazy atr, wytwarzanie tego związku i jego różnych postaci stałych |
| LT3157566T (lt) | 2014-06-17 | 2019-08-12 | Vertex Pharmaceuticals Incorporated | Vėžio gydymo būdas, panaudojant chk1 ir atr inhibitorių derinį |
| JP6573618B2 (ja) * | 2014-09-09 | 2019-09-11 | アステラス製薬株式会社 | 尿失禁予防用及び／又は治療用新規医薬組成物 |
| WO2016193844A1 (en) | 2015-05-29 | 2016-12-08 | Pfizer Inc. | Novel heterocyclic compounds as inhibitors of vanin-1 enzyme |
| HK1258570A1 (zh) | 2015-09-30 | 2019-11-15 | Vertex Pharmaceuticals Inc. | 使用dna损伤剂及atr抑制剂的组合治疗癌症的方法 |
| BR112018016475A2 (en) | 2016-02-12 | 2018-12-26 | Cytokinetics, Incorporated | tetrahydroisoquinoline derivatives |
| EP3484876A1 (en) | 2016-07-14 | 2019-05-22 | Pfizer Inc | Novel pyrimidine carboxamides as inhibitors of vanin-1 enzyme |
| JP7770928B2 (ja) * | 2019-06-19 | 2025-11-17 | エフ． ホフマン－ラ ロシュ アーゲー | デジタルバイオマーカー |
| JP7687968B2 (ja) | 2019-06-19 | 2025-06-03 | エフ． ホフマン－ラ ロシュ アーゲー | デジタルバイオマーカー |
| WO2020254344A1 (en) | 2019-06-19 | 2020-12-24 | F. Hoffmann-La Roche Ag | Digital biomarker |
| WO2021007477A1 (en) | 2019-07-11 | 2021-01-14 | E-Scape Bio, Inc. | Indazoles and azaindazoles as lrrk2 inhibitors |
| WO2022099011A1 (en) | 2020-11-06 | 2022-05-12 | Cytokinetics, Inc. | Bicyclic 1,4-diazepanones and therapeutic uses thereof |
| WO2023107705A1 (en) | 2021-12-10 | 2023-06-15 | Incyte Corporation | Bicyclic amines as cdk12 inhibitors |
| TW202448488A (zh) * | 2023-04-17 | 2024-12-16 | 美商雅利斯塔製藥公司 | 用於治療肌肉萎縮症及記憶損傷之方法及組合物 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070173465A9 (en) * | 1995-10-11 | 2007-07-26 | Monahan Sean D | Expression of zeta negative and zeta positive nucleic acids using a dystrophin gene |
| US20090029345A1 (en) * | 2006-08-01 | 2009-01-29 | Alan Russell | Modulating skeletal muscle |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7201898B2 (en) * | 2000-06-01 | 2007-04-10 | The University Of North Carolina At Chapel Hill | Methods and compounds for controlled release of recombinant parvovirus vectors |
| CN1283793C (zh) * | 2002-06-03 | 2006-11-08 | 北京大学 | 具有骨骼肌刺激活性和免疫调节作用的趋化素样因子超家族 |
| JP2007501805A (ja) * | 2003-08-08 | 2007-02-01 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | ピリジルピペラジニルウレア |
| ES2558517T3 (es) * | 2006-08-02 | 2016-02-04 | Cytokinetics, Inc. | Ciertas entidades químicas, composiciones y métodos que comprenden imidazopirimidinas |
| US8299248B2 (en) * | 2006-08-02 | 2012-10-30 | Cytokinetics, Incorporated | Certain 1H-imidazo[4,5-b]pyrazin-2(3H)-ones and 1H-imidazo[4,5-b]pyrazin-2-ols and methods for their use |
| KR20100044251A (ko) * | 2007-08-15 | 2010-04-29 | 싸이토키네틱스, 인코포레이티드 | 특정 화학 물질, 조성물 및 방법 |
| NL2001694C2 (en) * | 2008-06-18 | 2009-12-22 | Nasophlex B V | Ear stimulator for producing a stimulation signal to an ear. |
| AR081331A1 (es) * | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| AR081626A1 (es) * | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
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2013
- 2013-04-01 SG SG10201701101YA patent/SG10201701101YA/en unknown
- 2013-04-01 JP JP2015503681A patent/JP6345645B2/ja not_active Expired - Fee Related
- 2013-04-01 KR KR1020147027435A patent/KR20160046693A/ko not_active Abandoned
- 2013-04-01 US US14/389,805 patent/US20150065525A1/en not_active Abandoned
- 2013-04-01 EA EA201491605A patent/EA031183B1/ru not_active IP Right Cessation
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- 2013-04-01 EP EP13773086.7A patent/EP2834269A4/en not_active Withdrawn
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- 2013-04-01 CN CN201810509450.1A patent/CN108553467A/zh active Pending
- 2013-04-01 SG SG11201406270YA patent/SG11201406270YA/en unknown
- 2013-04-01 HK HK15106936.7A patent/HK1206364A1/xx unknown
- 2013-04-01 CA CA2868507A patent/CA2868507A1/en not_active Abandoned
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2014
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- 2014-10-01 PH PH12014502217A patent/PH12014502217A1/en unknown
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2017
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- 2017-12-07 AU AU2017272286A patent/AU2017272286B2/en not_active Ceased
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2018
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2019
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2020
- 2020-06-17 JP JP2020104620A patent/JP2020147607A/ja active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070173465A9 (en) * | 1995-10-11 | 2007-07-26 | Monahan Sean D | Expression of zeta negative and zeta positive nucleic acids using a dystrophin gene |
| US20090029345A1 (en) * | 2006-08-01 | 2009-01-29 | Alan Russell | Modulating skeletal muscle |
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| AU2013243671A1 (en) | 2014-10-16 |
| MX354965B (es) | 2018-03-27 |
| JP2015516957A (ja) | 2015-06-18 |
| US20170266192A1 (en) | 2017-09-21 |
| SG11201406270YA (en) | 2014-10-30 |
| KR20160046693A (ko) | 2016-04-29 |
| EP2834269A4 (en) | 2015-12-30 |
| US20150065525A1 (en) | 2015-03-05 |
| IL267876A (en) | 2019-09-26 |
| HK1206364A1 (en) | 2016-01-08 |
| EP2834269A1 (en) | 2015-02-11 |
| WO2013151938A1 (en) | 2013-10-10 |
| JP2020147607A (ja) | 2020-09-17 |
| CN104379597A (zh) | 2015-02-25 |
| AU2017272286B2 (en) | 2019-05-09 |
| AU2013243671B2 (en) | 2017-09-21 |
| PH12014502217A1 (en) | 2015-01-12 |
| AU2017272286A1 (en) | 2018-01-04 |
| JP2018131460A (ja) | 2018-08-23 |
| SG10201701101YA (en) | 2017-04-27 |
| BR112014024552A2 (pt) | 2017-09-19 |
| JP6345645B2 (ja) | 2018-06-20 |
| IL267876B (en) | 2021-03-25 |
| MX2014011881A (es) | 2016-07-20 |
| IL234885A0 (en) | 2014-12-31 |
| EA201491605A1 (ru) | 2015-03-31 |
| CA2868507A1 (en) | 2013-10-10 |
| CN108553467A (zh) | 2018-09-21 |
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