JP6861703B2 - Ｔｇｒ５修飾物質およびその使用方法 - Google Patents
Ｔｇｒ５修飾物質およびその使用方法 Download PDFInfo
- Publication number
- JP6861703B2 JP6861703B2 JP2018517671A JP2018517671A JP6861703B2 JP 6861703 B2 JP6861703 B2 JP 6861703B2 JP 2018517671 A JP2018517671 A JP 2018517671A JP 2018517671 A JP2018517671 A JP 2018517671A JP 6861703 B2 JP6861703 B2 JP 6861703B2
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- 0 C*[C@](C*1)[C@@]2C1[C@](C)C2 Chemical compound C*[C@](C*1)[C@@]2C1[C@](C)C2 0.000 description 6
- QUAACMKIRHXEPE-CGJKNLMHSA-N CC[C@H]([C@H](C[C@@H](CC1)O)[C@@]1(C)C(C1)C2C(CC[C@@H]3[C@H](C)CCC(O)=O)[C@]3(C)[C@H]1O)[C@H]2O Chemical compound CC[C@H]([C@H](C[C@@H](CC1)O)[C@@]1(C)C(C1)C2C(CC[C@@H]3[C@H](C)CCC(O)=O)[C@]3(C)[C@H]1O)[C@H]2O QUAACMKIRHXEPE-CGJKNLMHSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
- C07J9/005—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J31/00—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring
- C07J31/006—Normal steroids containing one or more sulfur atoms not belonging to a hetero ring not covered by C07J31/003
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0005—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton
- C07J41/0016—Oximes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
- C07J41/0061—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives one of the carbon atoms being part of an amide group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0094—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 containing nitrile radicals, including thiocyanide radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J71/00—Steroids in which the cyclopenta(a)hydrophenanthrene skeleton is condensed with a heterocyclic ring
- C07J71/0005—Oxygen-containing hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J41/00—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring
- C07J41/0033—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005
- C07J41/0055—Normal steroids containing one or more nitrogen atoms not belonging to a hetero ring not covered by C07J41/0005 the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Toxicology (AREA)
- Immunology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Transplantation (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Child & Adolescent Psychology (AREA)
- Urology & Nephrology (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562182081P | 2015-06-19 | 2015-06-19 | |
| US62/182,081 | 2015-06-19 | ||
| EP15305976 | 2015-06-24 | ||
| EP15305976.1 | 2015-06-24 | ||
| PCT/US2016/037812 WO2016205475A2 (en) | 2015-06-19 | 2016-06-16 | Tgr5 modulators and methods of use thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018518537A JP2018518537A (ja) | 2018-07-12 |
| JP2018518537A5 JP2018518537A5 (enExample) | 2021-01-14 |
| JP6861703B2 true JP6861703B2 (ja) | 2021-04-21 |
Family
ID=53489911
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018517671A Active JP6861703B2 (ja) | 2015-06-19 | 2016-06-16 | Ｔｇｒ５修飾物質およびその使用方法 |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP3310801B1 (enExample) |
| JP (1) | JP6861703B2 (enExample) |
| KR (1) | KR20180043247A (enExample) |
| CN (1) | CN107771180B (enExample) |
| AU (1) | AU2016280806B2 (enExample) |
| CA (1) | CA2989167A1 (enExample) |
| IL (1) | IL256085B (enExample) |
| MX (1) | MX380972B (enExample) |
| PL (1) | PL3310801T3 (enExample) |
| PT (1) | PT3310801T (enExample) |
| SI (1) | SI3310801T1 (enExample) |
| TW (1) | TW201700447A (enExample) |
| UY (1) | UY36738A (enExample) |
| WO (1) | WO2016205475A2 (enExample) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX381239B (es) | 2014-11-19 | 2025-03-12 | Nzp Uk Ltd | Esteroides de 6.alfa.-alquil-6,7-diona como intermedios para la producción de moduladores esteroideos del receptor x farnesoide (fxr). |
| EA034739B1 (ru) | 2014-11-19 | 2020-03-16 | ЭнЗедПи ЮКей ЛИМИТЕД | 6-альфа-алкил-3,7-дионовые стероиды в качестве промежуточных соединений для получения стероидных модуляторов fxr |
| JP6724004B2 (ja) | 2014-11-19 | 2020-07-15 | エヌゼットピー ユーケー リミテッド | ステロイドＦＸＲモジュレーター製造のための中間体としての５β−６−アルキル−７−ヒドロキシ−３−オンステロイド |
| EA033427B1 (ru) | 2014-11-19 | 2019-10-31 | Nzp Uk Ltd | 6-алкил-7-гидрокси-4-ен-3-оновые стероиды в качестве промежуточных соединений для получения стероидных модуляторов fxr |
| KR20170099909A (ko) | 2014-11-26 | 2017-09-01 | 이난타 파마슈티칼스, 인코포레이티드 | Fxr/tgr5 작용제로서의 담즙산 유사체 및 이의 이용 방법 |
| US11578097B2 (en) | 2014-11-26 | 2023-02-14 | Enanta Pharmaceuticals, Inc. | Tetrazole derivatives of bile acids as FXR/TGR5 agonists and methods of use thereof |
| US10208081B2 (en) | 2014-11-26 | 2019-02-19 | Enanta Pharmaceuticals, Inc. | Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof |
| HK1245100A1 (zh) | 2015-02-11 | 2018-08-24 | Enanta Pharmaceuticals, Inc. | 作为fxr/tgr5激动剂的胆汁酸类似物及其使用方法 |
| NZ735126A (en) | 2015-03-31 | 2022-10-28 | Enanta Pharm Inc | Bile acid derivatives as fxr/tgr5 agonists and methods of use thereof |
| EP3290429A1 (en) * | 2015-04-28 | 2018-03-07 | Jiangsu Hansoh Pharmaceutical Group Co., Ltd. | Cholic acid derivative, and preparation method and medical use thereof |
| US10800807B2 (en) | 2015-06-19 | 2020-10-13 | Intercept Pharmaceuticals, Inc. | TGR5 modulators and methods of use thereof |
| US20170196893A1 (en) * | 2016-01-07 | 2017-07-13 | The Board Of Trustees Of The Leland Stanford Junior University | Treatment of inflammatory demyelinating disease with agonists of farnesoid x receptor |
| US10323061B2 (en) | 2016-02-23 | 2019-06-18 | Enanta Pharmaceuticals, Inc. | Heteroaryl containing bile acid analogs as FXR/TGR5 agonists and methods of use thereof |
| US10323060B2 (en) | 2016-02-23 | 2019-06-18 | Enanta Pharmaceuticals, Inc. | Benzoic acid derivatives of bile acid as FXR/TGR5 agonists and methods of use thereof |
| GB201608777D0 (en) | 2016-05-18 | 2016-06-29 | Dextra Lab Ltd | Compounds |
| AU2017368069B2 (en) | 2016-11-29 | 2021-07-08 | Enanta Pharmaceuticals, Inc. | Process for preparation of sulfonylurea bile acid derivatives |
| WO2018152171A1 (en) | 2017-02-14 | 2018-08-23 | Enanta Pharmaceuticals, Inc. | Bile acid derivatives as fxr agonists and methods of use thereof |
| JP7136802B2 (ja) | 2017-04-07 | 2022-09-13 | エナンタ ファーマシューティカルズ インコーポレイテッド | スルホニルカルバマート胆汁酸誘導体の調製のためのプロセス |
| CN109134572A (zh) * | 2017-06-19 | 2019-01-04 | 中国科学院上海药物研究所 | 胆酸衍生物及其制备方法和用途 |
| GB201812382D0 (en) | 2018-07-30 | 2018-09-12 | Nzp Uk Ltd | Compounds |
| WO2020041673A1 (en) * | 2018-08-23 | 2020-02-27 | President And Fellows Of Harvard College | Compositions and methods related to cholic acid-7-sulfate as a treatment for diabetes |
| WO2020117945A1 (en) * | 2018-12-04 | 2020-06-11 | President And Fellows Of Harvard College | Synthetic derivatives of cholic acid 7-sulfate and uses thereof |
| WO2021046678A1 (zh) * | 2019-09-09 | 2021-03-18 | 邦泰生物工程(深圳)有限公司 | 一种合成鹅去氧胆酸的方法及其应用 |
| JP2022552655A (ja) | 2019-10-07 | 2022-12-19 | キャリーオペ，インク． | Ｇｐｒ１１９アゴニスト |
| TW202140440A (zh) | 2020-02-28 | 2021-11-01 | 美商克力歐普股份有限公司 | Gpr40激動劑 |
| CN112341512A (zh) * | 2020-04-13 | 2021-02-09 | 苏州恩泰新材料科技有限公司 | 由海豹胆酸制备鹅去氧胆酸的方法 |
| CN112300237A (zh) * | 2020-04-13 | 2021-02-02 | 苏州恩泰新材料科技有限公司 | 海豹胆酸的制备方法及其应用 |
| AU2021275038A1 (en) | 2020-05-19 | 2022-12-22 | Kallyope, Inc. | AMPK activators |
| CA3183575A1 (en) | 2020-06-26 | 2021-12-30 | Iyassu Sebhat | Ampk activators |
| CN114276402B (zh) * | 2022-01-05 | 2023-11-14 | 厦门大学 | 一种甾体衍生物及其在制备抗肿瘤药物中的应用 |
| CN120271652B (zh) * | 2025-05-27 | 2025-10-03 | 华南理工大学 | 噁二唑-甾体化合物、药物组合物和用途 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101679476B (zh) * | 2007-01-19 | 2014-05-07 | 英特塞普特医药品公司 | 23取代的胆汁酸作为tgr5调节剂及其使用方法 |
| EP1947108A1 (en) * | 2007-01-19 | 2008-07-23 | Intercept Pharmaceuticals, Inc. | TGR5 modulators and methods of use thereof |
| CN104370990A (zh) * | 2008-11-19 | 2015-02-25 | 英特塞普特医药品公司 | G蛋白偶联受体5(tgr5)调节剂及其使用方法 |
| CN106661364A (zh) * | 2014-06-25 | 2017-05-10 | 3M创新有限公司 | 包含三嗪基团的共聚物以及包含它们的组合物 |
| US10208081B2 (en) * | 2014-11-26 | 2019-02-19 | Enanta Pharmaceuticals, Inc. | Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof |
| KR20170099909A (ko) * | 2014-11-26 | 2017-09-01 | 이난타 파마슈티칼스, 인코포레이티드 | Fxr/tgr5 작용제로서의 담즙산 유사체 및 이의 이용 방법 |
| US11578097B2 (en) * | 2014-11-26 | 2023-02-14 | Enanta Pharmaceuticals, Inc. | Tetrazole derivatives of bile acids as FXR/TGR5 agonists and methods of use thereof |
| EP3290429A1 (en) * | 2015-04-28 | 2018-03-07 | Jiangsu Hansoh Pharmaceutical Group Co., Ltd. | Cholic acid derivative, and preparation method and medical use thereof |
| CN107531743B (zh) * | 2015-04-29 | 2020-05-05 | 正大天晴药业集团股份有限公司 | 鹅去氧胆酸衍生物 |
-
2016
- 2016-06-16 CN CN201680035575.4A patent/CN107771180B/zh active Active
- 2016-06-16 TW TW105118959A patent/TW201700447A/zh unknown
- 2016-06-16 SI SI201631166T patent/SI3310801T1/sl unknown
- 2016-06-16 EP EP16762910.4A patent/EP3310801B1/en active Active
- 2016-06-16 PT PT167629104T patent/PT3310801T/pt unknown
- 2016-06-16 PL PL16762910T patent/PL3310801T3/pl unknown
- 2016-06-16 WO PCT/US2016/037812 patent/WO2016205475A2/en not_active Ceased
- 2016-06-16 KR KR1020187001542A patent/KR20180043247A/ko not_active Withdrawn
- 2016-06-16 MX MX2017016611A patent/MX380972B/es unknown
- 2016-06-16 AU AU2016280806A patent/AU2016280806B2/en active Active
- 2016-06-16 CA CA2989167A patent/CA2989167A1/en not_active Abandoned
- 2016-06-16 JP JP2018517671A patent/JP6861703B2/ja active Active
- 2016-06-17 UY UY0001036738A patent/UY36738A/es not_active Application Discontinuation
-
2017
- 2017-12-04 IL IL256085A patent/IL256085B/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| AU2016280806B2 (en) | 2021-01-28 |
| UY36738A (es) | 2017-01-31 |
| MX2017016611A (es) | 2018-05-15 |
| TW201700447A (zh) | 2017-01-01 |
| IL256085B (en) | 2021-02-28 |
| EP3310801A2 (en) | 2018-04-25 |
| MX380972B (es) | 2025-03-12 |
| KR20180043247A (ko) | 2018-04-27 |
| PL3310801T3 (pl) | 2021-11-22 |
| AU2016280806A1 (en) | 2018-01-04 |
| CN107771180B (zh) | 2021-03-23 |
| CN107771180A (zh) | 2018-03-06 |
| PT3310801T (pt) | 2021-06-18 |
| JP2018518537A (ja) | 2018-07-12 |
| EP3310801B1 (en) | 2021-04-07 |
| WO2016205475A2 (en) | 2016-12-22 |
| WO2016205475A3 (en) | 2017-02-23 |
| SI3310801T1 (sl) | 2021-10-29 |
| CA2989167A1 (en) | 2016-12-22 |
| IL256085A (en) | 2018-02-28 |
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