CA2945527C - Mdm2 inhibitors and therapeutic methods using the same - Google Patents
Mdm2 inhibitors and therapeutic methods using the same Download PDFInfo
- Publication number
- CA2945527C CA2945527C CA2945527A CA2945527A CA2945527C CA 2945527 C CA2945527 C CA 2945527C CA 2945527 A CA2945527 A CA 2945527A CA 2945527 A CA2945527 A CA 2945527A CA 2945527 C CA2945527 C CA 2945527C
- Authority
- CA
- Canada
- Prior art keywords
- compound
- mdm2
- compounds
- pharmaceutically acceptable
- cancer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- 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
- C07D487/10—Spiro-condensed systems
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
-
- 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
- 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
- C07D471/12—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 three hetero rings
- C07D471/20—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/10—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy
- A61N2005/1092—Details
- A61N2005/1098—Enhancing the effect of the particle by an injected agent or implanted device
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Radiology & Medical Imaging (AREA)
- Pathology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461980747P | 2014-04-17 | 2014-04-17 | |
| US61/980,747 | 2014-04-17 | ||
| PCT/US2015/026098 WO2015161032A1 (en) | 2014-04-17 | 2015-04-16 | Mdm2 inhibitors and therapeutic methods using the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2945527A1 CA2945527A1 (en) | 2015-10-22 |
| CA2945527C true CA2945527C (en) | 2022-05-17 |
Family
ID=54321424
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2945527A Active CA2945527C (en) | 2014-04-17 | 2015-04-16 | Mdm2 inhibitors and therapeutic methods using the same |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US9745314B2 (enExample) |
| EP (1) | EP3131544B1 (enExample) |
| JP (2) | JP6694827B2 (enExample) |
| KR (2) | KR102389552B1 (enExample) |
| CN (2) | CN106794171B (enExample) |
| AU (1) | AU2015247646B2 (enExample) |
| CA (1) | CA2945527C (enExample) |
| ES (1) | ES2712973T3 (enExample) |
| IL (2) | IL248211B (enExample) |
| MX (2) | MX373045B (enExample) |
| SG (2) | SG10201913742TA (enExample) |
| WO (1) | WO2015161032A1 (enExample) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0811643D0 (en) | 2008-06-25 | 2008-07-30 | Cancer Rec Tech Ltd | New therapeutic agents |
| CN106794171B (zh) * | 2014-04-17 | 2020-03-24 | 密歇根大学董事会 | Mdm2抑制剂和使用其的治疗方法 |
| EA038071B1 (ru) | 2014-08-21 | 2021-07-01 | Бёрингер Ингельхайм Интернациональ Гмбх | СОЕДИНЕНИЕ СПИРО[3H-ИНДОЛ-3,2'-ПИРРОЛИДИН]-2(1H)-ОНА И ЕГО ПРОИЗВОДНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ MDM2-p53 |
| US9962380B2 (en) * | 2015-09-23 | 2018-05-08 | Wisconsin Alumni Research Foundation | Methods for treating cognitive deficits associated with fragile X syndrome |
| GB201517217D0 (en) | 2015-09-29 | 2015-11-11 | Astex Therapeutics Ltd And Cancer Res Technology Ltd | Pharmaceutical compounds |
| GB201517216D0 (en) | 2015-09-29 | 2015-11-11 | Cancer Res Technology Ltd And Astex Therapeutics Ltd | Pharmaceutical compounds |
| MX377009B (es) | 2015-10-09 | 2025-03-07 | Boehringer Ingelheim Int | Nuevos compuestos de espiro[3h-indol-3,2´-pirrolidin]-2(1h)-ona y derivados como inhibidores de mdm2-p53. |
| JP7037500B2 (ja) * | 2016-04-06 | 2022-03-16 | ザ リージェンツ オブ ザ ユニヴァシティ オブ ミシガン | Mdm2タンパク質分解剤 |
| CN109152843A (zh) | 2016-05-20 | 2019-01-04 | 豪夫迈·罗氏有限公司 | Protac抗体缀合物及其使用方法 |
| GB201704966D0 (en) | 2017-03-28 | 2017-05-10 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| GB201704965D0 (en) | 2017-03-28 | 2017-05-10 | Astex Therapeutics Ltd | Pharmaceutical compounds |
| CA3087110A1 (en) * | 2017-12-29 | 2019-07-04 | Gan & Lee Pharmaceuticals | Compounds capable of being used as tumor inhibitor, preparation method thereof, and application thereof |
| EP3511334A1 (en) * | 2018-01-16 | 2019-07-17 | Adamed sp. z o.o. | 1,2,3',5'-tetrahydro-2'h-spiro[indole-3,1'-pyrrolo[3,4-c]pyrrole]-2,3'-dione compounds as therapeutic agents activating tp53 |
| KR102039696B1 (ko) | 2018-04-23 | 2019-11-04 | 충남대학교산학협력단 | 세포내 결핵균 제어를 위한 p53 발현 조절 가능한 조성물 (K279-1558) 또는 방법 |
| EP3672591B1 (en) | 2018-07-31 | 2024-02-14 | Ascentage Pharma (Suzhou) Co., Ltd. | Synergistic antitumor effect of bcl-2 inhibitor combined with rituximab and/or bendamustine or bcl-2 inhibitor combined with chop |
| CN110776507B (zh) | 2018-07-31 | 2020-12-18 | 苏州亚盛药业有限公司 | Bcl-2抑制剂与化疗药的组合产品及其在预防和/或治疗疾病中的用途 |
| CN114522167A (zh) | 2018-07-31 | 2022-05-24 | 苏州亚盛药业有限公司 | Bcl-2抑制剂或Bcl-2/Bcl-xL抑制剂与BTK抑制剂的组合产品及其用途 |
| BR112020018978A2 (pt) * | 2018-07-31 | 2021-03-02 | Ascentage Pharma (Suzhou) Co., Ltd. | produto de combinação que compreende um inibidor de bcl-2 e um inibidor de mdm2 e uso dos ditos inibidores na prevenção e/ou tratamento de câncer |
| MX2020013728A (es) * | 2018-08-08 | 2021-05-27 | Ascentage Pharma Suzhou Co Ltd | Combinacion de inmunoterapias con inhibidores de mdm2. |
| TWI750539B (zh) * | 2018-11-23 | 2021-12-21 | 大陸商蘇州亞盛藥業有限公司 | 新穎藥物組成物及其用途 |
| CN111320635B (zh) * | 2018-12-14 | 2021-03-30 | 苏州亚盛药业有限公司 | 用于治疗骨关节炎的化合物 |
| US20210311020A1 (en) * | 2019-02-24 | 2021-10-07 | Ascentage Pharma (Suzhou) Co., Ltd. | Treatment methods and biomarkers for mdm2 inhibitors |
| US11787814B2 (en) | 2019-07-11 | 2023-10-17 | Ascentage Pharma (Suzhou) Co., Ltd. | Method for preparing 2-indolinospirone compound and intermediate thereof |
| CN112237579B (zh) * | 2019-07-19 | 2022-03-29 | 苏州亚盛药业有限公司 | 药物组合及其用途 |
| EP4003332A4 (en) | 2019-07-26 | 2023-05-10 | Ascentage Pharma (Suzhou) Co., Ltd. | PHARMACEUTICAL COMPOSITION OF AN MDM2 INHIBITOR AND ITS USE TO PREVENT AND/OR TREAT DISEASES |
| WO2021104442A1 (en) * | 2019-11-27 | 2021-06-03 | Ascentage Pharma (Suzhou) Co., Ltd. | Method and compositions for predicting anti-cancer efficacy of compounds targeting apoptosis pathway |
| US11850239B2 (en) | 2019-12-19 | 2023-12-26 | Ascentage Pharma (Suzhou) Co., Ltd. | MDM2 inhibitor and a platinum compound for cancer treatment |
| GB201919219D0 (en) | 2019-12-23 | 2020-02-05 | Otsuka Pharma Co Ltd | Cancer biomarkers |
| EP4041736A4 (en) * | 2020-01-23 | 2023-06-07 | Ascentage Pharma (Suzhou) Co., Ltd. | AMORPHOUS FORM OR CRYSTALLINE FORM OF 2-INDOLINOLINOLOLYLSPIRONONE COMPOUNDS OR THEIR SALTS, SOLVENT COMPLEXES |
| WO2021175192A1 (en) * | 2020-03-02 | 2021-09-10 | Ascentage Pharma (Suzhou) Co., Ltd. | Treatment methods and biomarkers for mdm2 inhibitors |
| MX2022011602A (es) * | 2020-03-19 | 2023-01-04 | Kymera Therapeutics Inc | Degradadores de la proteína de homólogo de ratón de minuto 2 (mdm2) y usos de los mismos. |
| US20230149356A1 (en) * | 2020-04-14 | 2023-05-18 | Ascentage Pharma (Suzhou) Co., Ltd. | Novel medical use of mdm2 inhibitors |
| CN113801120B (zh) * | 2020-06-15 | 2024-03-22 | 苏州亚盛药业有限公司 | Mdm2抑制剂的微悬浮液以及治疗应用 |
| AU2021333983A1 (en) | 2020-08-27 | 2023-01-05 | Otsuka Pharmaceutical Co., Ltd. | Biomarkers for cancer therapy using MDM2 antagonists |
| CN112022812B (zh) * | 2020-11-03 | 2021-01-29 | 上海亚盛医药科技有限公司 | 一种包含杂环类化合物的组合物、其制备方法和应用 |
| WO2022170108A1 (en) * | 2021-02-04 | 2022-08-11 | Aileron Therapeutics, Inc. | Peptidomimetic macrocycles and uses thereof in prevention of radiation injury |
| EP4294513A1 (en) | 2021-02-19 | 2023-12-27 | Mevion Medical Systems, Inc. | Gantry for a particle therapy system |
| GB202103080D0 (en) | 2021-03-04 | 2021-04-21 | Otsuka Pharma Co Ltd | Cancer biomarkers |
| EP4382126A4 (en) | 2021-08-02 | 2025-07-30 | Ascentage Pharma Suzhou Co Ltd | PHARMACEUTICAL COMBINATION AND ITS USE |
| WO2023056069A1 (en) | 2021-09-30 | 2023-04-06 | Angiex, Inc. | Degrader-antibody conjugates and methods of using same |
| CN116421598B (zh) * | 2022-01-11 | 2024-08-30 | 苏州亚盛药业有限公司 | 用于治疗aml-mrc和mds的方法 |
| WO2024240858A1 (en) | 2023-05-23 | 2024-11-28 | Valerio Therapeutics | Protac molecules directed against dna damage repair system and uses thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US3989816A (en) | 1975-06-19 | 1976-11-02 | Nelson Research & Development Company | Vehicle composition containing 1-substituted azacycloheptan-2-ones |
| US4444762A (en) | 1980-04-04 | 1984-04-24 | Nelson Research & Development Company | Vehicle composition containing 1-substituted azacyclopentan-2-ones |
| US6605712B1 (en) | 1990-12-20 | 2003-08-12 | Arch Development Corporation | Gene transcription and ionizing radiation: methods and compositions |
| SG176463A1 (en) | 2005-02-22 | 2011-12-29 | Univ Michigan | Small molecule inhibitors of mdm2 and uses thereof |
| EP2130822A1 (en) | 2005-12-01 | 2009-12-09 | F. Hoffmann-La Roche AG | 2,4,5-triphenyl imidazoline derivatives as inhibitors of the interaction between p53 and mdm2 proteins for use as anticancer agents |
| ES2350504T3 (es) * | 2006-03-13 | 2011-01-24 | F. Hoffmann-La Roche Ag | Derivados de espiroindolinona. |
| JP2009530236A (ja) * | 2006-03-13 | 2009-08-27 | エフ.ホフマン−ラ ロシュ アーゲー | スピロインドリノン誘導体 |
| WO2008036168A2 (en) * | 2006-08-30 | 2008-03-27 | The Regents Of The University Of Michigan | New small molecule inhibitors of mdm2 and the uses thereof |
| US7737174B2 (en) | 2006-08-30 | 2010-06-15 | The Regents Of The University Of Michigan | Indole inhibitors of MDM2 and the uses thereof |
| US8222288B2 (en) | 2006-08-30 | 2012-07-17 | The Regents Of The University Of Michigan | Small molecule inhibitors of MDM2 and the uses thereof |
| US20080206794A1 (en) | 2006-09-15 | 2008-08-28 | Renovar Incorporated | Systems And Methods For Characterizing Contrast Induced-Nephropathy |
| US20080188506A1 (en) * | 2007-02-07 | 2008-08-07 | Qingjie Ding | Spiroindolinone derivatives |
| KR101380013B1 (ko) | 2008-09-18 | 2014-04-10 | 에프. 호프만-라 로슈 아게 | 치환 피롤리딘-2-카르복사미드 |
| US8354444B2 (en) | 2008-09-18 | 2013-01-15 | Hoffmann-La Roche Inc. | Substituted pyrrolidine-2-carboxamides |
| US8076482B2 (en) * | 2009-04-23 | 2011-12-13 | Hoffmann-La Roche Inc. | 3,3′-spiroindolinone derivatives |
| RU2553269C2 (ru) * | 2009-11-12 | 2015-06-10 | Дзе Риджентс Оф Дзе Юниверсити Оф Мичиган | Спирооксиндольные антагонисты mdm2 |
| US8088815B2 (en) | 2009-12-02 | 2012-01-03 | Hoffman-La Roche Inc. | Spiroindolinone pyrrolidines |
| RU2012147597A (ru) * | 2010-04-09 | 2014-05-20 | Дзе Риджентс Оф Дзе Юниверсити Оф Мичиган | Биомаркеры для ингибиторов mdm2, использующиеся для лечения заболевания |
| US8217044B2 (en) * | 2010-04-28 | 2012-07-10 | Hoffmann-La Roche Inc. | Spiroindolinone pyrrolidines |
| JO2998B1 (ar) | 2010-06-04 | 2016-09-05 | Amgen Inc | مشتقات بيبيريدينون كمثبطات mdm2 لعلاج السرطان |
| US20120046306A1 (en) | 2010-08-18 | 2012-02-23 | David Joseph Bartkovitz | Substituted Heteroaryl Spiropyrrolidine MDM2 Antagonists |
| JP2014500870A (ja) | 2010-11-12 | 2014-01-16 | ザ、リージェンツ、オブ、ザ、ユニバーシティ、オブ、ミシガン | スピロ−オキシインドールmdm2アンタゴニスト |
| TR201807311T4 (tr) * | 2011-03-10 | 2018-06-21 | Daiichi Sankyo Co Ltd | Dispiropirolidin derivesi. |
| JP2014513699A (ja) * | 2011-05-11 | 2014-06-05 | ザ リージェンツ オブ ザ ユニバーシティ オブ ミシガン | スピロ−オキシインドールmdm2アンタゴニスト |
| WO2013049250A1 (en) | 2011-09-27 | 2013-04-04 | Amgen Inc. | Heterocyclic compounds as mdm2 inhibitors for the treatment of cancer |
| BR112016004593B1 (pt) * | 2013-09-04 | 2022-12-06 | Daiichi Sankyo Company, Limited | Métodos para reagir um composto, para hidrolisar um composto ou um sal do mesmo, para produzir um composto e para preparar um composto |
| CN106794171B (zh) * | 2014-04-17 | 2020-03-24 | 密歇根大学董事会 | Mdm2抑制剂和使用其的治疗方法 |
-
2015
- 2015-04-16 CN CN201580032547.2A patent/CN106794171B/zh active Active
- 2015-04-16 SG SG10201913742TA patent/SG10201913742TA/en unknown
- 2015-04-16 MX MX2016013457A patent/MX373045B/es active IP Right Grant
- 2015-04-16 EP EP15779988.3A patent/EP3131544B1/en active Active
- 2015-04-16 SG SG11201608667SA patent/SG11201608667SA/en unknown
- 2015-04-16 KR KR1020167031180A patent/KR102389552B1/ko active Active
- 2015-04-16 US US14/688,553 patent/US9745314B2/en active Active
- 2015-04-16 ES ES15779988T patent/ES2712973T3/es active Active
- 2015-04-16 KR KR1020227012871A patent/KR102599945B1/ko active Active
- 2015-04-16 WO PCT/US2015/026098 patent/WO2015161032A1/en not_active Ceased
- 2015-04-16 AU AU2015247646A patent/AU2015247646B2/en active Active
- 2015-04-16 JP JP2016562752A patent/JP6694827B2/ja active Active
- 2015-04-16 CN CN202010081463.0A patent/CN111718354A/zh active Pending
- 2015-04-16 CA CA2945527A patent/CA2945527C/en active Active
-
2016
- 2016-10-06 IL IL24821116A patent/IL248211B/en active IP Right Grant
- 2016-10-13 MX MX2020003939A patent/MX2020003939A/es unknown
-
2019
- 2019-09-19 IL IL269462A patent/IL269462B/en active IP Right Grant
-
2020
- 2020-02-28 JP JP2020033622A patent/JP6909323B2/ja active Active
Also Published As
| Publication number | Publication date |
|---|---|
| IL248211B (en) | 2019-10-31 |
| SG11201608667SA (en) | 2016-11-29 |
| MX2020003939A (es) | 2020-08-13 |
| JP6694827B2 (ja) | 2020-05-20 |
| US9745314B2 (en) | 2017-08-29 |
| CN106794171A (zh) | 2017-05-31 |
| KR102599945B1 (ko) | 2023-11-09 |
| IL269462A (en) | 2019-11-28 |
| JP6909323B2 (ja) | 2021-07-28 |
| KR102389552B1 (ko) | 2022-04-22 |
| CA2945527A1 (en) | 2015-10-22 |
| KR20220054697A (ko) | 2022-05-03 |
| IL248211A0 (en) | 2016-11-30 |
| SG10201913742TA (en) | 2020-03-30 |
| JP2017511360A (ja) | 2017-04-20 |
| KR20160136450A (ko) | 2016-11-29 |
| US20150299211A1 (en) | 2015-10-22 |
| CN111718354A (zh) | 2020-09-29 |
| CN106794171B (zh) | 2020-03-24 |
| WO2015161032A1 (en) | 2015-10-22 |
| EP3131544A1 (en) | 2017-02-22 |
| EP3131544B1 (en) | 2018-12-12 |
| MX373045B (es) | 2020-05-26 |
| JP2020100662A (ja) | 2020-07-02 |
| IL269462B (en) | 2021-05-31 |
| ES2712973T3 (es) | 2019-05-17 |
| AU2015247646A1 (en) | 2016-10-27 |
| MX2016013457A (es) | 2017-05-04 |
| NZ724963A (en) | 2021-10-29 |
| AU2015247646B2 (en) | 2019-06-06 |
| EP3131544A4 (en) | 2017-08-30 |
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