ES2712973T3 - Inhibidores de MDM2 y métodos terapéuticos que usan los mismos - Google Patents
Inhibidores de MDM2 y métodos terapéuticos que usan los mismos Download PDFInfo
- Publication number
- ES2712973T3 ES2712973T3 ES15779988T ES15779988T ES2712973T3 ES 2712973 T3 ES2712973 T3 ES 2712973T3 ES 15779988 T ES15779988 T ES 15779988T ES 15779988 T ES15779988 T ES 15779988T ES 2712973 T3 ES2712973 T3 ES 2712973T3
- Authority
- ES
- Spain
- Prior art keywords
- compounds
- mdm2
- compound according
- cancer
- structural formula
- 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
- NJSLYZGIMWTLCA-ZCYQVTIMSA-N OC(C(CC1)(CC2)CCC12NC([C@@H]([C@@H]1c(cccc2Cl)c2F)NC2(CCCCC2)[C@@]1(C(C(N1)=C2)=CCC2Cl)C1=O)=O)=O Chemical compound OC(C(CC1)(CC2)CCC12NC([C@@H]([C@@H]1c(cccc2Cl)c2F)NC2(CCCCC2)[C@@]1(C(C(N1)=C2)=CCC2Cl)C1=O)=O)=O NJSLYZGIMWTLCA-ZCYQVTIMSA-N 0.000 description 1
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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461980747P | 2014-04-17 | 2014-04-17 | |
| PCT/US2015/026098 WO2015161032A1 (en) | 2014-04-17 | 2015-04-16 | Mdm2 inhibitors and therapeutic methods using the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2712973T3 true ES2712973T3 (es) | 2019-05-17 |
Family
ID=54321424
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES15779988T Active ES2712973T3 (es) | 2014-04-17 | 2015-04-16 | Inhibidores de MDM2 y métodos terapéuticos que usan los mismos |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US9745314B2 (OSRAM) |
| EP (1) | EP3131544B1 (OSRAM) |
| JP (2) | JP6694827B2 (OSRAM) |
| KR (2) | KR102599945B1 (OSRAM) |
| CN (2) | CN111718354A (OSRAM) |
| AU (1) | AU2015247646B2 (OSRAM) |
| CA (1) | CA2945527C (OSRAM) |
| ES (1) | ES2712973T3 (OSRAM) |
| IL (2) | IL248211B (OSRAM) |
| MX (2) | MX373045B (OSRAM) |
| SG (2) | SG11201608667SA (OSRAM) |
| WO (1) | WO2015161032A1 (OSRAM) |
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 |
| US9745314B2 (en) * | 2014-04-17 | 2017-08-29 | The Regents Of The University Of Michigan | MDM2 inhibitors and therapeutic methods using the same |
| PT3183254T (pt) | 2014-08-21 | 2019-08-29 | Boehringer Ingelheim Int | Novos compostos de espiro[3h-indole-3,2¿-pirrolidin]-2(1h)-ona e derivados como inibidores de mdm2-p53 |
| US9962380B2 (en) * | 2015-09-23 | 2018-05-08 | Wisconsin Alumni Research Foundation | Methods for treating cognitive deficits associated with fragile X syndrome |
| GB201517216D0 (en) | 2015-09-29 | 2015-11-11 | Cancer Res Technology Ltd And Astex Therapeutics Ltd | Pharmaceutical compounds |
| GB201517217D0 (en) | 2015-09-29 | 2015-11-11 | Astex Therapeutics Ltd And Cancer Res Technology Ltd | Pharmaceutical compounds |
| TWI737635B (zh) | 2015-10-09 | 2021-09-01 | 德商百靈佳殷格翰國際股份有限公司 | 作為mdm2－p53抑制劑之新穎螺﹝3h－吲哚－3，2´－吡咯啶﹞－2（1h）－酮化合物及其衍生物 |
| CN113788818A (zh) * | 2016-04-06 | 2021-12-14 | 密执安大学评议会 | Mdm2蛋白质降解剂 |
| CN118436801A (zh) | 2016-05-20 | 2024-08-06 | 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 |
| CN112041320B (zh) * | 2017-12-29 | 2023-05-23 | 甘李药业股份有限公司 | 一种可用作肿瘤抑制剂的化合物及其制备方法与应用 |
| 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 |
| CN110772521A (zh) | 2018-07-31 | 2020-02-11 | 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 |
| TWI752335B (zh) * | 2018-07-31 | 2022-01-11 | 大陸商蘇州亞盛藥業有限公司 | Bcl-2抑制劑與MDM2抑制劑的組合產品及其在預防及/或治療疾病中的用途 |
| UA125241C2 (uk) | 2018-07-31 | 2022-02-02 | Есентейдж Фарма (Сучжоу) Ко., Лтд. | СИНЕРГІЧНИЙ ПРОТИПУХЛИННИЙ ЕФЕКТ ІНГІБІТОРА Bcl-2 В ПОЄДНАННІ З РИТУКСИМАБОМ ТА/АБО БЕНДАМУСТИНОМ АБО ІНГІБІТОРА Bcl-2 В ПОЄДНАННІ З CHOP |
| AU2019314819A1 (en) | 2018-07-31 | 2020-10-22 | Ascentage Pharma (Suzhou) Co., Ltd. | Combination product of Bcl-2 inhibitor and chemotherapeutic agent and use thereof in the prevention and/or treatment of diseases |
| WO2020030016A1 (en) * | 2018-08-08 | 2020-02-13 | Ascentage Pharma (Suzhou) Co., Ltd. | Combination of immunotherapies with mdm2 inhibitors |
| AU2019384292A1 (en) | 2018-11-23 | 2021-01-14 | Ascentage Pharma (Suzhou) Co., Ltd. | Novel pharmaceutical composition and use thereof |
| JP2021528380A (ja) * | 2018-12-14 | 2021-10-21 | アセンテージ ファーマ（スーチョウ）カンパニー，リミティド | 変形性関節症を治療するための化合物 |
| WO2020169073A1 (en) * | 2019-02-24 | 2020-08-27 | 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 |
| US12233047B2 (en) * | 2019-07-19 | 2025-02-25 | Ascentage Pharma (Suzhou) Co., Ltd. | Pharmaceutical combination and use thereof |
| CN112294965B (zh) * | 2019-07-26 | 2023-03-14 | 苏州亚盛药业有限公司 | Mdm2抑制剂的药物组合物及其在预防和/或治疗疾病中的用途 |
| 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 |
| TWI777380B (zh) * | 2020-01-23 | 2022-09-11 | 大陸商蘇州亞盛藥業有限公司 | 2-吲哚啉螺環酮類化合物之結晶形式 |
| WO2021175192A1 (en) * | 2020-03-02 | 2021-09-10 | Ascentage Pharma (Suzhou) Co., Ltd. | Treatment methods and biomarkers for mdm2 inhibitors |
| PH12022552458A1 (en) * | 2020-03-19 | 2024-01-22 | Kymera Therapeutics Inc | Mdm2 degraders and uses thereof |
| WO2021208911A1 (en) * | 2020-04-14 | 2021-10-21 | Ascentage Pharma (Suzhou) Co., Ltd. | Novel medical use of mdm2 inhibitors |
| WO2021254277A1 (en) * | 2020-06-15 | 2021-12-23 | Ascentage Pharma (Suzhou) Co., Ltd. | Microsuspension of an mdm2 inhibitor and therapeutic applications thereof |
| KR20230058124A (ko) | 2020-08-27 | 2023-05-02 | 오츠카 세이야쿠 가부시키가이샤 | Mdm2 길항제를 사용하는 암 치료를 위한 생체표지자 |
| 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 |
| JP2024511277A (ja) | 2021-02-19 | 2024-03-13 | メビオン・メディカル・システムズ・インコーポレーテッド | 粒子線治療システムのためのガントリー |
| GB202103080D0 (en) | 2021-03-04 | 2021-04-21 | Otsuka Pharma Co Ltd | Cancer biomarkers |
| JP2024528174A (ja) | 2021-08-02 | 2024-07-26 | アセンテージ ファーマ（スーチョウ）カンパニー，リミティド | 医薬組合せおよびその使用 |
| WO2023056069A1 (en) | 2021-09-30 | 2023-04-06 | Angiex, Inc. | Degrader-antibody conjugates and methods of using same |
| US20250114329A1 (en) * | 2022-01-11 | 2025-04-10 | Ascentage Pharma (Suzhou) Co., Ltd | Methods for treating aml-mrc and mds |
| 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 |
|---|---|---|---|---|
| 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 |
| AU2006319248B2 (en) | 2005-12-01 | 2012-09-27 | F.Hoffman-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. |
| KR101052706B1 (ko) * | 2006-03-13 | 2011-08-01 | 에프. 호프만-라 로슈 아게 | 스피로인돌리논 유도체 |
| CA2661354C (en) * | 2006-08-30 | 2012-12-18 | 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 |
| US8354444B2 (en) | 2008-09-18 | 2013-01-15 | Hoffmann-La Roche Inc. | Substituted pyrrolidine-2-carboxamides |
| AU2009294673B2 (en) | 2008-09-18 | 2014-08-14 | F. Hoffmann-La Roche Ag | Substituted pyrrolidine-2-carboxamides |
| US8076482B2 (en) * | 2009-04-23 | 2011-12-13 | Hoffmann-La Roche Inc. | 3,3′-spiroindolinone derivatives |
| BR112012011317A2 (pt) | 2009-11-12 | 2019-09-24 | Univ Michigan Regents | antagonistas espiro-oxindóis de mdm2 |
| US8088815B2 (en) | 2009-12-02 | 2012-01-03 | Hoffman-La Roche Inc. | Spiroindolinone pyrrolidines |
| CN103153302A (zh) * | 2010-04-09 | 2013-06-12 | 密歇根大学董事会 | 针对用于治疗疾病的mdm2抑制剂的生物标记 |
| 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 |
| AU2011326395B2 (en) | 2010-11-12 | 2016-01-07 | Ascenta Licensing Corporation | Spiro-oxindole MDM2 antagonists |
| WO2012121361A1 (ja) * | 2011-03-10 | 2012-09-13 | 第一三共株式会社 | ジスピロピロリジン誘導体 |
| 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 |
| CA2923398C (en) * | 2013-09-04 | 2019-01-15 | Daiichi Sankyo Company, Limited | Method for producing spirooxindole derivative |
| US9745314B2 (en) * | 2014-04-17 | 2017-08-29 | The Regents Of The University Of Michigan | MDM2 inhibitors and therapeutic methods using the same |
-
2015
- 2015-04-16 US US14/688,553 patent/US9745314B2/en active Active
- 2015-04-16 CA CA2945527A patent/CA2945527C/en active Active
- 2015-04-16 CN CN202010081463.0A patent/CN111718354A/zh active Pending
- 2015-04-16 JP JP2016562752A patent/JP6694827B2/ja active Active
- 2015-04-16 EP EP15779988.3A patent/EP3131544B1/en active Active
- 2015-04-16 SG SG11201608667SA patent/SG11201608667SA/en unknown
- 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 CN CN201580032547.2A patent/CN106794171B/zh active Active
- 2015-04-16 MX MX2016013457A patent/MX373045B/es active IP Right Grant
- 2015-04-16 AU AU2015247646A patent/AU2015247646B2/en active Active
- 2015-04-16 ES ES15779988T patent/ES2712973T3/es active Active
- 2015-04-16 KR KR1020167031180A patent/KR102389552B1/ko active Active
- 2015-04-16 SG SG10201913742TA patent/SG10201913742TA/en unknown
-
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 |
|---|---|
| SG10201913742TA (en) | 2020-03-30 |
| JP6909323B2 (ja) | 2021-07-28 |
| KR102599945B1 (ko) | 2023-11-09 |
| JP2017511360A (ja) | 2017-04-20 |
| MX373045B (es) | 2020-05-26 |
| KR20160136450A (ko) | 2016-11-29 |
| WO2015161032A1 (en) | 2015-10-22 |
| IL248211A0 (en) | 2016-11-30 |
| JP6694827B2 (ja) | 2020-05-20 |
| US20150299211A1 (en) | 2015-10-22 |
| CN106794171B (zh) | 2020-03-24 |
| CA2945527C (en) | 2022-05-17 |
| IL269462A (en) | 2019-11-28 |
| JP2020100662A (ja) | 2020-07-02 |
| CN106794171A (zh) | 2017-05-31 |
| IL248211B (en) | 2019-10-31 |
| AU2015247646A1 (en) | 2016-10-27 |
| CA2945527A1 (en) | 2015-10-22 |
| NZ724963A (en) | 2021-10-29 |
| MX2016013457A (es) | 2017-05-04 |
| EP3131544A4 (en) | 2017-08-30 |
| CN111718354A (zh) | 2020-09-29 |
| SG11201608667SA (en) | 2016-11-29 |
| EP3131544A1 (en) | 2017-02-22 |
| MX2020003939A (es) | 2020-08-13 |
| US9745314B2 (en) | 2017-08-29 |
| IL269462B (en) | 2021-05-31 |
| AU2015247646B2 (en) | 2019-06-06 |
| EP3131544B1 (en) | 2018-12-12 |
| KR102389552B1 (ko) | 2022-04-22 |
| KR20220054697A (ko) | 2022-05-03 |
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