RU2658920C2 - Амиды в качестве модуляторов натриевых каналов - Google Patents
Амиды в качестве модуляторов натриевых каналов Download PDFInfo
- Publication number
- RU2658920C2 RU2658920C2 RU2015136779A RU2015136779A RU2658920C2 RU 2658920 C2 RU2658920 C2 RU 2658920C2 RU 2015136779 A RU2015136779 A RU 2015136779A RU 2015136779 A RU2015136779 A RU 2015136779A RU 2658920 C2 RU2658920 C2 RU 2658920C2
- Authority
- RU
- Russia
- Prior art keywords
- another embodiment
- alkyl
- benzamido
- pain
- compound
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- 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
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A61P9/06—Antiarrhythmics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/58—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/64—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring with carbon atoms of carboxamide groups and singly-bound oxygen atoms, bound in ortho-position to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361759062P | 2013-01-31 | 2013-01-31 | |
| US61/759,062 | 2013-01-31 | ||
| PCT/US2014/013667 WO2014120820A1 (en) | 2013-01-31 | 2014-01-29 | Amides as modulators of sodium channels |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2015136779A RU2015136779A (ru) | 2017-03-07 |
| RU2658920C2 true RU2658920C2 (ru) | 2018-06-26 |
Family
ID=50114569
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2015136779A RU2658920C2 (ru) | 2013-01-31 | 2014-01-29 | Амиды в качестве модуляторов натриевых каналов |
Country Status (15)
| Country | Link |
|---|---|
| US (2) | US9108903B2 (enExample) |
| EP (1) | EP2951155B1 (enExample) |
| JP (1) | JP6346622B2 (enExample) |
| KR (1) | KR102226588B1 (enExample) |
| CN (1) | CN104968647B (enExample) |
| AR (1) | AR094668A1 (enExample) |
| AU (1) | AU2014212431B2 (enExample) |
| BR (1) | BR112015018284B1 (enExample) |
| CA (1) | CA2898653C (enExample) |
| IL (1) | IL240196B (enExample) |
| MX (1) | MX359882B (enExample) |
| RU (1) | RU2658920C2 (enExample) |
| SG (1) | SG11201505954RA (enExample) |
| TW (1) | TWI659945B (enExample) |
| WO (1) | WO2014120820A1 (enExample) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SMT201700256T1 (it) | 2013-01-31 | 2017-09-07 | Vertex Pharma | Piridone ammidi come modulatori di canali del sodio |
| NZ710111A (en) | 2013-01-31 | 2020-08-28 | Vertex Pharma | Quinoline and quinoxaline amides as modulators of sodium channels |
| JP6337109B2 (ja) | 2013-07-19 | 2018-06-06 | 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 | ナトリウムチャネルの調節剤としてのスルホンアミド |
| JP6463580B2 (ja) | 2013-12-13 | 2019-02-06 | 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 | ナトリウムチャネルの調節剤として有用なピリドンアミドのプロドラッグ |
| BR112019024016A2 (pt) | 2017-05-16 | 2020-06-09 | Vertex Pharma | amidas de piridona deuteradas e profármacos das mesmas como moduladores de canais de sódio |
| CA3069720A1 (en) | 2017-07-11 | 2019-01-17 | Vertex Pharmaceuticals Incorporated | Carboxamides as modulators of sodium channels |
| EP3752152A1 (en) | 2018-02-12 | 2020-12-23 | Vertex Pharmaceuticals Incorporated | A method of treating pain |
| EP3873893A1 (en) | 2018-11-02 | 2021-09-08 | Merck Sharp & Dohme Corp. | 2-amino-n-heteroaryl-nicotinamides as nav1.8 inhibitors |
| US12344595B2 (en) | 2018-11-02 | 2025-07-01 | Merck Sharp & Dohme Llc | 2-amino-n-phenyl-nicotinamides as NAV1.8 inhibitors |
| EP3907218A4 (en) * | 2019-01-04 | 2022-09-21 | Jiangsu Hengrui Medicine Co., Ltd. | 6-OXO-1,6-DIHYDROPYRIDAZINE DERIVATIVE, METHOD FOR PREPARATION AND MEDICAL USE |
| US12441703B2 (en) | 2019-01-10 | 2025-10-14 | Vertex Pharmaceuticals Incorporated | Carboxamides as modulators of sodium channels |
| WO2020146612A1 (en) | 2019-01-10 | 2020-07-16 | Vertex Pharmaceuticals Incorporated | Esters and carbamates as modulators of sodium channels |
| CN112996776B (zh) * | 2019-02-20 | 2024-03-15 | 福建盛迪医药有限公司 | 6-氧代-1,6-二氢哒嗪类前药衍生物、其制备方法及其在医药上的应用 |
| WO2020176763A1 (en) | 2019-02-27 | 2020-09-03 | Vertex Pharmaceuticals Incorporated | Dosage form comprising prodrug of na 1.8 sodium channel inhibitor |
| WO2020219867A1 (en) | 2019-04-25 | 2020-10-29 | Vertex Pharmaceuticals Incorporated | Pyridone amide co-crystal compositions for the treatment of pain |
| AU2020346951A1 (en) * | 2019-09-12 | 2022-04-28 | Shanghai Jeyou Pharmaceutical Co., Ltd. | Pyridine oxynitride, preparation method therefor and use thereof |
| DK4069691T3 (da) | 2019-12-06 | 2024-10-28 | Vertex Pharma | Substituerede tetrahydrofuraner som modulatorer af natriumkanaler |
| CN114437062B (zh) * | 2020-04-30 | 2024-05-17 | 成都海博为药业有限公司 | 一种可作为钠通道调节剂的化合物及其用途 |
| IL299180A (en) | 2020-06-17 | 2023-02-01 | Merck Sharp & Dohme Llc | 2-OXOIMIDAZOLIDINE-4-CARBOXAMIDES AS NAV1.8 INHIBITORS |
| JP2023530319A (ja) | 2020-06-17 | 2023-07-14 | メルク・シャープ・アンド・ドーム・エルエルシー | Ｎａｖ１．８阻害剤としての２－オキソ－オキサゾリジン－５－カルボキサミド |
| CN113880771B (zh) * | 2020-07-03 | 2023-09-19 | 福建盛迪医药有限公司 | 一种选择性Nav抑制剂的结晶形式及其制备方法 |
| CN114031518B (zh) * | 2020-12-08 | 2023-08-18 | 成都海博为药业有限公司 | 一种苄胺或苄醇衍生物及其用途 |
| CN112225695B (zh) * | 2020-12-15 | 2021-03-02 | 上海济煜医药科技有限公司 | 一种氮氧化合物及其制备方法和用途 |
| TW202300147A (zh) * | 2021-03-11 | 2023-01-01 | 大陸商上海濟煜醫藥科技有限公司 | 吡啶氮氧化合物晶型及其應用 |
| CA3217565A1 (en) | 2021-05-07 | 2022-11-10 | Ashok Arasappan | Cycloalkyl 3-oxopiperazine carboxamides and cycloheteroalkyl 3-oxopiperazine carboxamides as nav1.8 inhibitors |
| JP2024520649A (ja) | 2021-06-04 | 2024-05-24 | 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 | （２ｒ，３ｓ，４ｓ，５ｒ）－４－［［３－（３，４－ジフルオロ－２－メトキシ－フェニル）－４，５－ジメチル－５－（トリフルオロメチル）テトラヒドロフラン－２－カルボニル］アミノ］ピリジン－２－カルボキサミドを含む固体剤形及び投与レジメン |
| JP2024520648A (ja) | 2021-06-04 | 2024-05-24 | 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 | ナトリウムチャネルの調節因子としての置換テトラヒドロフラン－２－カルボキサミド |
| CA3221939A1 (en) | 2021-06-04 | 2022-12-08 | Vertex Pharmaceuticals Incorporated | N-(hydroxyalkyl (hetero)aryl) tetrahydrofuran carboxamide analogs as modulators of sodium channels |
| CN117794918A (zh) | 2021-06-04 | 2024-03-29 | 沃泰克斯药物股份有限公司 | 经取代的四氢呋喃类似物作为钠通道调节剂 |
| EP4347033A1 (en) | 2021-06-04 | 2024-04-10 | Vertex Pharmaceuticals Incorporated | Hydroxy and (halo)alkoxy substituted tetrahydrofurans as modulators of sodium channels |
| MA64853B1 (fr) | 2021-06-04 | 2025-11-28 | Vertex Pharmaceuticals Incorporated | N-(hydroxyalkyl (hétéro)aryl) tétrahydrofuran carboxamides utilisés en tant que modulateurs de canaux sodiques |
| EP4511115A1 (en) | 2022-04-22 | 2025-02-26 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| AU2023255771A1 (en) | 2022-04-22 | 2024-10-31 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| JP2025513455A (ja) | 2022-04-22 | 2025-04-24 | 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 | 疼痛の治療のためのヘテロアリール化合物 |
| JP2025513452A (ja) | 2022-04-22 | 2025-04-24 | 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 | 疼痛の治療のためのヘテロアリール化合物 |
| CR20240512A (es) | 2022-04-25 | 2025-03-03 | Siteone Therapeutics Inc | Inhibidores de amida heterocíclica bicíclica de sodio activado por voltaje 1.8 (nav1.8) para el tratamiento del dolor |
| EP4630405A1 (en) | 2022-12-06 | 2025-10-15 | Vertex Pharmaceuticals Incorporated | Process for the synthesis of substituted tetrahydrofuran modulators of sodium channels |
| WO2024153856A1 (en) * | 2023-01-18 | 2024-07-25 | Orion Corporation | Process for the preparation of 3-(4,5-dichloro-2-(4-(trifluoromethoxy)phenoxy)benzamido)pyridine 1-oxide |
| WO2025090511A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Methods of preparing modulators of sodium channels and solid forms of the same for treating pain |
| WO2025090465A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| WO2025090480A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| WO2025090516A1 (en) | 2023-10-23 | 2025-05-01 | Vertex Pharmaceuticals Incorporated | Methods of preparing compounds for treating pain and solid forms thereof |
| WO2025122953A1 (en) | 2023-12-07 | 2025-06-12 | Vertex Pharmaceuticals Incorporated | Dosing regimens and formulations of suzetrigine for use in the treatment of acute and chronic pain |
| WO2025160286A1 (en) | 2024-01-24 | 2025-07-31 | Siteone Therapeutics, Inc. | 2-aryl cycloalkyl and heterocycloalkyl inhibitors of nav1.8 for the treatment of pain |
| US20260001877A1 (en) | 2024-06-28 | 2026-01-01 | Vertex Pharmaceuticals Incorporated | Heteroaryl compounds for the treatment of pain |
| WO2026013449A2 (en) | 2024-07-11 | 2026-01-15 | Sea4Us - Biotecnologia E Recursos Marinhos, Sa | Oxazolidone-derived compounds and their use in the treatment of chronic and acute pain |
| WO2026030525A1 (en) | 2024-07-31 | 2026-02-05 | Vertex Pharmaceuticals Incorporated | Zilvetrigine dosage forms and dosing regimens for treating pain |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009049181A1 (en) * | 2007-10-11 | 2009-04-16 | Vertex Pharmaceuticals Incorporated | Amides useful as inhibitors of voltage-gated sodium channels |
| WO2010137351A1 (en) * | 2009-05-29 | 2010-12-02 | Raqualia Pharma Inc. | Aryl substituted carboxamide derivatives as calcium or sodium channel blockers |
| RU2010118467A (ru) * | 2007-10-11 | 2011-11-20 | Вертекс Фармасьютикалз Инкорпорейтед (Us) | Ариламиды, пригодные в качестве ингибиторов потенциалзависимых натриевых каналов |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2511231A (en) * | 1949-03-26 | 1950-06-13 | Eastman Kodak Co | 1-cyanophenyl-3-acylamino-5-pyrazolone couplers for color photography |
| KR20080109918A (ko) | 2006-04-11 | 2008-12-17 | 버텍스 파마슈티칼스 인코포레이티드 | 전압 개폐 나트륨 채널의 억제제로서 유용한 조성물 |
| EP2227453B1 (en) | 2007-10-11 | 2016-03-09 | Vertex Pharmaceuticals Incorporated | Heteroaryl amides useful as inhibitors of voltage-gated sodium channels |
-
2014
- 2014-01-29 CA CA2898653A patent/CA2898653C/en active Active
- 2014-01-29 RU RU2015136779A patent/RU2658920C2/ru active
- 2014-01-29 TW TW103103690A patent/TWI659945B/zh not_active IP Right Cessation
- 2014-01-29 KR KR1020157023600A patent/KR102226588B1/ko not_active Expired - Fee Related
- 2014-01-29 CN CN201480006878.4A patent/CN104968647B/zh active Active
- 2014-01-29 US US14/167,741 patent/US9108903B2/en active Active
- 2014-01-29 AR ARP140100282A patent/AR094668A1/es unknown
- 2014-01-29 MX MX2015009591A patent/MX359882B/es active IP Right Grant
- 2014-01-29 BR BR112015018284-4A patent/BR112015018284B1/pt not_active IP Right Cessation
- 2014-01-29 SG SG11201505954RA patent/SG11201505954RA/en unknown
- 2014-01-29 JP JP2015556113A patent/JP6346622B2/ja active Active
- 2014-01-29 AU AU2014212431A patent/AU2014212431B2/en active Active
- 2014-01-29 EP EP14704981.1A patent/EP2951155B1/en active Active
- 2014-01-29 WO PCT/US2014/013667 patent/WO2014120820A1/en not_active Ceased
-
2015
- 2015-07-27 US US14/809,841 patent/US9421196B2/en active Active
- 2015-07-28 IL IL240196A patent/IL240196B/en active IP Right Grant
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009049181A1 (en) * | 2007-10-11 | 2009-04-16 | Vertex Pharmaceuticals Incorporated | Amides useful as inhibitors of voltage-gated sodium channels |
| RU2010118467A (ru) * | 2007-10-11 | 2011-11-20 | Вертекс Фармасьютикалз Инкорпорейтед (Us) | Ариламиды, пригодные в качестве ингибиторов потенциалзависимых натриевых каналов |
| WO2010137351A1 (en) * | 2009-05-29 | 2010-12-02 | Raqualia Pharma Inc. | Aryl substituted carboxamide derivatives as calcium or sodium channel blockers |
Also Published As
| Publication number | Publication date |
|---|---|
| IL240196B (en) | 2019-08-29 |
| AU2014212431B2 (en) | 2018-04-05 |
| CN104968647B (zh) | 2018-01-26 |
| AR094668A1 (es) | 2015-08-19 |
| CA2898653A1 (en) | 2014-08-07 |
| KR102226588B1 (ko) | 2021-03-11 |
| SG11201505954RA (en) | 2015-08-28 |
| MX2015009591A (es) | 2016-04-15 |
| CN104968647A (zh) | 2015-10-07 |
| BR112015018284A2 (pt) | 2017-07-18 |
| EP2951155B1 (en) | 2019-06-19 |
| US9108903B2 (en) | 2015-08-18 |
| IL240196A0 (en) | 2015-09-24 |
| AU2014212431A1 (en) | 2015-08-06 |
| EP2951155A1 (en) | 2015-12-09 |
| WO2014120820A1 (en) | 2014-08-07 |
| JP2016508500A (ja) | 2016-03-22 |
| WO2014120820A9 (en) | 2015-07-02 |
| CA2898653C (en) | 2021-09-28 |
| TWI659945B (zh) | 2019-05-21 |
| US20150328196A1 (en) | 2015-11-19 |
| MX359882B (es) | 2018-10-15 |
| NZ710293A (en) | 2020-09-25 |
| HK1217692A1 (en) | 2017-01-20 |
| US9421196B2 (en) | 2016-08-23 |
| KR20150118964A (ko) | 2015-10-23 |
| JP6346622B2 (ja) | 2018-06-20 |
| BR112015018284B1 (pt) | 2023-03-07 |
| TW201443005A (zh) | 2014-11-16 |
| US20140221435A1 (en) | 2014-08-07 |
| RU2015136779A (ru) | 2017-03-07 |
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