EA032838B1 - Макроциклические ингибиторы lrrk2-киназы - Google Patents
Макроциклические ингибиторы lrrk2-киназы Download PDFInfo
- Publication number
- EA032838B1 EA032838B1 EA201790626A EA201790626A EA032838B1 EA 032838 B1 EA032838 B1 EA 032838B1 EA 201790626 A EA201790626 A EA 201790626A EA 201790626 A EA201790626 A EA 201790626A EA 032838 B1 EA032838 B1 EA 032838B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- alkyl
- compound
- halogen
- optionally
- independently substituted
- Prior art date
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- HDOWRFHMPULYOA-UHFFFAOYSA-N piperidin-4-ol Chemical compound OC1CCNCC1 HDOWRFHMPULYOA-UHFFFAOYSA-N 0.000 description 1
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- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
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- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
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- 159000000001 potassium salts Chemical class 0.000 description 1
- VZOPRCCTKLAGPN-ZFJVMAEJSA-L potassium;sodium;(2r,3r)-2,3-dihydroxybutanedioate;tetrahydrate Chemical compound O.O.O.O.[Na+].[K+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O VZOPRCCTKLAGPN-ZFJVMAEJSA-L 0.000 description 1
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- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- LZFIOSVZIQOVFW-UHFFFAOYSA-N propyl 2-hydroxybenzoate Chemical class CCCOC(=O)C1=CC=CC=C1O LZFIOSVZIQOVFW-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
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- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
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- 125000000168 pyrrolyl group Chemical group 0.000 description 1
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- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
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- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 235000011006 sodium potassium tartrate Nutrition 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
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- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
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- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
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- 239000002600 sunflower oil Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
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- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- NSILYQWHARROMG-QMMMGPOBSA-N tert-butyl (3s)-3-(hydroxymethyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN[C@H](CO)C1 NSILYQWHARROMG-QMMMGPOBSA-N 0.000 description 1
- PWQLFIKTGRINFF-UHFFFAOYSA-N tert-butyl 4-hydroxypiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(O)CC1 PWQLFIKTGRINFF-UHFFFAOYSA-N 0.000 description 1
- 125000006092 tetrahydro-1,1-dioxothienyl group Chemical group 0.000 description 1
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- 229940124597 therapeutic agent Drugs 0.000 description 1
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- WCNFFKHKJLERFM-UHFFFAOYSA-N thiomorpholinyl sulfone group Chemical group N1(CCSCC1)S(=O)(=O)N1CCSCC1 WCNFFKHKJLERFM-UHFFFAOYSA-N 0.000 description 1
- ZCAGUOCUDGWENZ-UHFFFAOYSA-N thiomorpholinyl sulfoxide group Chemical group N1(CCSCC1)S(=O)N1CCSCC1 ZCAGUOCUDGWENZ-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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Classifications
-
- 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
- A61K31/529—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim forming part of bridged ring systems
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
-
- 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
- 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
- C07D487/22—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 four or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14290279 | 2014-09-17 | ||
| PCT/EP2015/071349 WO2016042089A1 (en) | 2014-09-17 | 2015-09-17 | Macrocyclic lrrk2 kinase inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201790626A1 EA201790626A1 (ru) | 2017-07-31 |
| EA032838B1 true EA032838B1 (ru) | 2019-07-31 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201790626A EA032838B1 (ru) | 2014-09-17 | 2015-09-17 | Макроциклические ингибиторы lrrk2-киназы |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US10377772B2 (enExample) |
| EP (1) | EP3194405B1 (enExample) |
| JP (1) | JP2017529365A (enExample) |
| KR (1) | KR20170048599A (enExample) |
| CN (1) | CN107108641A (enExample) |
| AU (1) | AU2015316801B2 (enExample) |
| BR (1) | BR112017005299A2 (enExample) |
| CA (1) | CA2960777A1 (enExample) |
| DK (1) | DK3194405T3 (enExample) |
| EA (1) | EA032838B1 (enExample) |
| ES (1) | ES2717510T3 (enExample) |
| HU (1) | HUE043972T2 (enExample) |
| IL (1) | IL251054B (enExample) |
| MX (1) | MX2017003470A (enExample) |
| PL (1) | PL3194405T3 (enExample) |
| SG (1) | SG11201701936WA (enExample) |
| TR (1) | TR201904514T4 (enExample) |
| TW (1) | TW201625639A (enExample) |
| WO (1) | WO2016042089A1 (enExample) |
| ZA (1) | ZA201701841B (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111221514B (zh) * | 2020-01-13 | 2023-03-03 | 陕西心像信息科技有限公司 | 基于OsgEarth的三维可视化组件实现方法及系统 |
| CN115698020B (zh) * | 2020-01-31 | 2025-02-25 | 昂科迪塞恩精密医药公司(Opm) | 大环rip2-激酶抑制剂 |
| US12545689B2 (en) | 2020-05-06 | 2026-02-10 | Oncodesign Precision Medicine | Macrocyclic LRRK2 kinase inhibitors |
| JP2024512449A (ja) | 2021-03-18 | 2024-03-19 | レ ラボラトワール セルヴィエ | 大環状ｌｒｒｋ２キナーゼ阻害剤 |
| WO2023064768A1 (en) * | 2021-10-11 | 2023-04-20 | Baylor College Of Medicine | G-protein-coupled receptor regulators and methods of use thereof |
| WO2023073013A1 (en) * | 2021-10-27 | 2023-05-04 | H. Lundbeck A/S | Lrrk2 inhibitors |
| WO2023222005A1 (zh) * | 2022-05-18 | 2023-11-23 | 上海翊石医药科技有限公司 | 一种芳杂环类化合物及其中间体、药物组合物和用途 |
| AR130483A1 (es) | 2022-09-15 | 2024-12-11 | H Lundbeck As | Inhibidores de la cinasa con repeticiones ricas en leucina 2 (lrrk2) |
| WO2024218296A1 (en) * | 2023-04-20 | 2024-10-24 | H. Lundbeck A/S | Combination treatments comprising administration of leucine-rich repeat kinase 2 (lrrk2) inhibitors |
| AR132488A1 (es) * | 2023-04-20 | 2025-07-02 | H Lundbeck As | Inhibidores de la cinasa con repeticiones ricas en leucina 2 (lrrk2) |
| AR132487A1 (es) * | 2023-04-20 | 2025-07-02 | H Lundbeck As | Inhibidores de la cinasa con repeticiones ricas en leucina 2 (lrrk2) |
| AR132486A1 (es) * | 2023-04-20 | 2025-07-02 | H Lundbeck As | Inhibidores de la cinasa con repeticiones ricas en leucina 2 (lrrk2) |
Citations (2)
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|---|---|---|---|---|
| WO2013001310A1 (en) * | 2011-06-30 | 2013-01-03 | Centro Nacional De Investigaciones Oncológicas (Cnio) | Macrocyclic compounds and their use as cdk8 inhibitors |
| WO2013046029A1 (en) * | 2011-09-30 | 2013-04-04 | Ipsen Pharma S.A.S. | Macrocyclic lrrk2 kinase inhibitors |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IS2334B (is) | 1992-09-08 | 2008-02-15 | Vertex Pharmaceuticals Inc., (A Massachusetts Corporation) | Aspartyl próteasi hemjari af nýjum flokki súlfonamíða |
| SK283569B6 (sk) | 1993-10-01 | 2003-09-11 | Astra Aktiebolag | Spôsob spracovania jemne deleného práškového liečiva, zariadenie na vykonávanie tohto spôsobu a aglomeráty vyrobené týmto spôsobom |
| EP0729758A3 (en) | 1995-03-02 | 1997-10-29 | Pfizer | Pyrazolopyrimidines and pyrrolopyrimidines for the treatment of neuronal and other diseases |
| US6043358A (en) | 1995-11-01 | 2000-03-28 | Merck & Co., Inc. | Hexahydro-5-imino-1,4-heteroazepine derivatives as inhibitors of nitric oxide synthases |
| HU229024B1 (en) | 1996-07-24 | 2013-07-29 | Bristol Myers Squibb Pharma Co | Azolo-pyridimidines, pharmaceutical compositions containing the same and use thereof |
| GB9718913D0 (en) | 1997-09-05 | 1997-11-12 | Glaxo Group Ltd | Substituted oxindole derivatives |
| US6194410B1 (en) | 1998-03-11 | 2001-02-27 | Hoffman-La Roche Inc. | Pyrazolopyrimidine and pyrazolines and process for preparation thereof |
| US6369087B1 (en) | 1999-08-26 | 2002-04-09 | Robert R. Whittle | Alkoxy substituted benzimidazole compounds, pharmaceutical preparations containing the same, and methods of using the same |
| ES2294047T3 (es) | 2000-12-28 | 2008-04-01 | Ono Pharmaceutical Co., Ltd. | Un compuesto de ciclopenta (d) pirazolo(1,5-a) pirimidina como antagonista del receptor de crf. |
| WO2002100399A1 (en) * | 2001-06-12 | 2002-12-19 | Elan Pharmaceuticals, Inc. | Macrocycles useful in the treatment of alzheimer's disease |
| EP2316927B1 (en) | 2004-10-21 | 2014-11-05 | Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH) | Kaspp (lrrk2) gene, its production and use for the detection and treatment of neurodegenerative disorders |
| NO323175B1 (no) | 2004-12-23 | 2007-01-15 | Jan O Aasly | Framgangsmate for a pavise en mutasjon som forarsaker arvelig parkinsonisme |
| FI123725B (fi) | 2005-08-01 | 2013-10-15 | Reijo Viljanen | Menetelmä sahalaitteen terän jännittämiseksi ja ohjaamiseksi sekä ohjaus- ja jännityslaitteet |
| ES2506040T3 (es) | 2005-11-16 | 2014-10-13 | Cti Biopharma Corp. | Derivados de pirimidina ligados a oxígeno |
| WO2009127642A2 (en) | 2008-04-15 | 2009-10-22 | Cellzome Limited | Use of lrrk2 inhibitors for neurodegenerative diseases |
| SG179120A1 (en) | 2009-09-29 | 2012-05-30 | Glaxo Group Ltd | Novel compounds |
| KR102015402B1 (ko) * | 2010-05-20 | 2019-08-28 | 어레이 바이오파마 인크. | Trk 키나제 저해제로서의 매크로시클릭 화합물 |
| BR112014007622A2 (pt) * | 2011-09-30 | 2017-04-04 | Oncodesign Sa | inibidores de flt3 cinase macrocíclicos |
-
2015
- 2015-09-17 KR KR1020177010322A patent/KR20170048599A/ko not_active Withdrawn
- 2015-09-17 CA CA2960777A patent/CA2960777A1/en not_active Abandoned
- 2015-09-17 DK DK15766801.3T patent/DK3194405T3/en active
- 2015-09-17 HU HUE15766801A patent/HUE043972T2/hu unknown
- 2015-09-17 TR TR2019/04514T patent/TR201904514T4/tr unknown
- 2015-09-17 JP JP2017515823A patent/JP2017529365A/ja active Pending
- 2015-09-17 ES ES15766801T patent/ES2717510T3/es active Active
- 2015-09-17 MX MX2017003470A patent/MX2017003470A/es unknown
- 2015-09-17 TW TW104130753A patent/TW201625639A/zh unknown
- 2015-09-17 WO PCT/EP2015/071349 patent/WO2016042089A1/en not_active Ceased
- 2015-09-17 EA EA201790626A patent/EA032838B1/ru not_active IP Right Cessation
- 2015-09-17 SG SG11201701936WA patent/SG11201701936WA/en unknown
- 2015-09-17 AU AU2015316801A patent/AU2015316801B2/en not_active Ceased
- 2015-09-17 US US15/511,879 patent/US10377772B2/en not_active Expired - Fee Related
- 2015-09-17 PL PL15766801T patent/PL3194405T3/pl unknown
- 2015-09-17 BR BR112017005299A patent/BR112017005299A2/pt not_active IP Right Cessation
- 2015-09-17 EP EP15766801.3A patent/EP3194405B1/en not_active Not-in-force
- 2015-09-17 CN CN201580061216.1A patent/CN107108641A/zh active Pending
-
2017
- 2017-03-09 IL IL251054A patent/IL251054B/en not_active IP Right Cessation
- 2017-03-15 ZA ZA2017/01841A patent/ZA201701841B/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013001310A1 (en) * | 2011-06-30 | 2013-01-03 | Centro Nacional De Investigaciones Oncológicas (Cnio) | Macrocyclic compounds and their use as cdk8 inhibitors |
| WO2013046029A1 (en) * | 2011-09-30 | 2013-04-04 | Ipsen Pharma S.A.S. | Macrocyclic lrrk2 kinase inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| RAGHAVA R KETHIRI, RAJAGOPAL BAKTHAVATCHALAM: "Leucine-rich repeat kinase 2 inhibitors: a review of recent patents (2011 – 2013)", EXPERT OPINION ON THERAPEUTIC PATENTS, vol. 24, no. 7, 1 July 2014 (2014-07-01), pages 745 - 757, XP055149873, ISSN: 13543776, DOI: 10.1517/13543776.2014.907275 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016042089A1 (en) | 2016-03-24 |
| CA2960777A1 (en) | 2016-03-24 |
| SG11201701936WA (en) | 2017-04-27 |
| TR201904514T4 (tr) | 2019-04-22 |
| AU2015316801A1 (en) | 2017-04-27 |
| ZA201701841B (en) | 2019-08-28 |
| IL251054B (en) | 2019-03-31 |
| BR112017005299A2 (pt) | 2017-12-12 |
| HUE043972T2 (hu) | 2019-09-30 |
| DK3194405T3 (en) | 2019-04-15 |
| PL3194405T4 (pl) | 2019-07-31 |
| US10377772B2 (en) | 2019-08-13 |
| JP2017529365A (ja) | 2017-10-05 |
| TW201625639A (zh) | 2016-07-16 |
| IL251054A0 (en) | 2017-04-30 |
| EP3194405A1 (en) | 2017-07-26 |
| EA201790626A1 (ru) | 2017-07-31 |
| CN107108641A (zh) | 2017-08-29 |
| AU2015316801B2 (en) | 2019-03-07 |
| EP3194405B1 (en) | 2018-12-26 |
| KR20170048599A (ko) | 2017-05-08 |
| MX2017003470A (es) | 2017-08-07 |
| US20170240565A1 (en) | 2017-08-24 |
| PL3194405T3 (pl) | 2019-07-31 |
| ES2717510T3 (es) | 2019-06-21 |
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| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
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