JP6843114B2 - ムスカリン作動薬 - Google Patents
ムスカリン作動薬 Download PDFInfo
- Publication number
- JP6843114B2 JP6843114B2 JP2018504992A JP2018504992A JP6843114B2 JP 6843114 B2 JP6843114 B2 JP 6843114B2 JP 2018504992 A JP2018504992 A JP 2018504992A JP 2018504992 A JP2018504992 A JP 2018504992A JP 6843114 B2 JP6843114 B2 JP 6843114B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- formula
- compound according
- salt
- hydrogen
- 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.)
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Links
- 0 CCCC(C*(*)C(OC*)=O)(C1)*(C)CC1=O Chemical compound CCCC(C*(*)C(OC*)=O)(C1)*(C)CC1=O 0.000 description 3
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Psychiatry (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1513743.3A GB201513743D0 (en) | 2015-08-03 | 2015-08-03 | Muscarinic agonists |
| GB1513743.3 | 2015-08-03 | ||
| PCT/GB2016/052385 WO2017021729A1 (en) | 2015-08-03 | 2016-08-03 | Muscarinic agonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018522033A JP2018522033A (ja) | 2018-08-09 |
| JP2018522033A5 JP2018522033A5 (2) | 2019-09-12 |
| JP6843114B2 true JP6843114B2 (ja) | 2021-03-17 |
Family
ID=54063149
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018504992A Active JP6843114B2 (ja) | 2015-08-03 | 2016-08-03 | ムスカリン作動薬 |
Country Status (10)
| Country | Link |
|---|---|
| US (3) | US10738029B2 (2) |
| EP (1) | EP3331529B1 (2) |
| JP (1) | JP6843114B2 (2) |
| CN (1) | CN108025004B (2) |
| AU (1) | AU2016304387B2 (2) |
| CA (1) | CA2994203C (2) |
| DK (1) | DK3331529T3 (2) |
| ES (1) | ES2894637T3 (2) |
| GB (1) | GB201513743D0 (2) |
| WO (1) | WO2017021729A1 (2) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2780015B1 (en) | 2011-11-18 | 2017-01-04 | Heptares Therapeutics Limited | Muscarinic m1 receptor agonists |
| GB201404922D0 (en) | 2014-03-19 | 2014-04-30 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201513743D0 (en) | 2015-08-03 | 2015-09-16 | Heptares Therapeutics Ltd | Muscarinic agonists |
| GB201513740D0 (en) * | 2015-08-03 | 2015-09-16 | Heptares Therapeutics Ltd | Muscarinic agonist |
| GB201519352D0 (en) | 2015-11-02 | 2015-12-16 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201617454D0 (en) | 2016-10-14 | 2016-11-30 | Heptares Therapeutics Limited | Pharmaceutical compounds |
| GB201709652D0 (en) * | 2017-06-16 | 2017-08-02 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| AU2018300980A1 (en) | 2017-07-12 | 2020-01-02 | Vanderbilt University | Antagonists of the muscarinic acetylcholine receptor M4 |
| AU2018352828A1 (en) * | 2017-10-17 | 2020-04-23 | Vanderbilt University | Antagonists of the muscarinic acetylcholine receptor M4 |
| IL273924B2 (en) | 2017-10-20 | 2024-07-01 | Univ Vanderbilt | Antagonists of the muscarinic acetylcholine receptor m4 |
| PT3768669T (pt) * | 2018-03-23 | 2023-04-24 | Pfizer | Derivados de piperazina azaspiro |
| GB201810245D0 (en) | 2018-06-22 | 2018-08-08 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201810239D0 (en) | 2018-06-22 | 2018-08-08 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201819961D0 (en) | 2018-12-07 | 2019-01-23 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201819960D0 (en) | 2018-12-07 | 2019-01-23 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB202020191D0 (en) | 2020-12-18 | 2021-02-03 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| WO2021070090A1 (en) * | 2019-10-09 | 2021-04-15 | Novartis Ag | 2-azaspiro[3.4]octane derivatives as m4 agonists |
| CN119390705A (zh) | 2019-10-09 | 2025-02-07 | 诺华股份有限公司 | 作为m4激动剂的5-氧杂-2-氮杂螺[3.4]辛烷衍生物 |
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| JPS56110674A (en) | 1980-01-24 | 1981-09-01 | Janssen Pharmaceutica Nv | Novel 11*cyclohexyl**44aryll44piperidine carboxylic acid derivative |
| US4369184A (en) | 1980-01-24 | 1983-01-18 | Janssen Pharmaceutica N.V. | 1-(Cyclohexyl)-4-aryl-4-piperidinecarboxylic acid derivatives |
| US5852029A (en) | 1990-04-10 | 1998-12-22 | Israel Institute For Biological Research | Aza spiro compounds acting on the cholinergic system with muscarinic agonist activity |
| GB9300194D0 (en) | 1993-01-06 | 1993-03-03 | Wyeth John & Brother Ltd | Piperazine derivatives |
| US5446051A (en) | 1994-05-31 | 1995-08-29 | Eli Lilly And Company | Aryl-spaced decahydroisoquinoline-3-carboxylic acids as excitatory amino acid receptor antagonists |
| JP2002515008A (ja) | 1994-10-27 | 2002-05-21 | メルク エンド カンパニー インコーポレーテッド | ムスカリン・アンタゴニスト |
| IL117149A0 (en) | 1995-02-23 | 1996-06-18 | Schering Corp | Muscarinic antagonists |
| US5889006A (en) | 1995-02-23 | 1999-03-30 | Schering Corporation | Muscarinic antagonists |
| WO1997016187A1 (en) | 1995-10-31 | 1997-05-09 | Merck & Co., Inc. | Muscarine antagonists |
| US5854245A (en) | 1996-06-28 | 1998-12-29 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| DE69734774D1 (de) | 1996-08-26 | 2006-01-05 | Pfizer | Spirocyclische dopaminrezeptor-subtyp-liganden |
| JP2002505684A (ja) | 1997-06-18 | 2002-02-19 | メルク エンド カンパニー インコーポレーテッド | α１ａアドレナリン受容体拮抗薬 |
| GB9715892D0 (en) | 1997-07-29 | 1997-10-01 | Zeneca Ltd | Heterocyclic compounds |
| WO1999032479A1 (en) | 1997-12-23 | 1999-07-01 | Alcon Laboratories, Inc. | Phthalimide-piperidine, -pyrrolidine and -azepine derivatives, their preparation and their use as muscarinic receptor (ant-)agonists |
| AU2307999A (en) | 1997-12-23 | 1999-07-12 | Alcon Laboratories, Inc. | Muscarinic agents and use thereof to treat glaucoma, myopia and various other conditions |
| WO1999032486A1 (en) | 1997-12-23 | 1999-07-01 | Alcon Laboratories, Inc. | Muscarinic agents and use thereof to treat glaucoma, myopia and various other conditions |
| WO1999032489A1 (en) | 1997-12-23 | 1999-07-01 | Alcon Laboratories, Inc. | Muscarinic agents and use thereof to treat glaucoma, myopia and various other conditions |
| CZ286152B6 (cs) | 1998-03-13 | 2000-01-12 | Miroslav Ing. Csc. Vlček | Transparentní a semitransparentní difrakční prvky |
| WO1999055674A1 (en) | 1998-04-28 | 1999-11-04 | Dainippon Pharmaceutical Co., Ltd. | 1-[(1-substituted-4-piperidinyl)methyl]-4-piperidine derivatives, process for producing the same, medicinal compositions containing the same and intermediates of these compounds |
| BR0010593A (pt) | 1999-05-04 | 2002-02-13 | Schering Corp | Terapia de combinação com antagonista de ccr5-interferon alfa peguilado para hiv |
| KR100439357B1 (ko) | 1999-05-04 | 2004-07-07 | 쉐링 코포레이션 | Ｃｃｒ５ 길항제로서 유용한 피페리딘 유도체 |
| US6387930B1 (en) | 1999-05-04 | 2002-05-14 | Schering Corporation | Piperidine derivatives useful as CCR5 antagonists |
| ES2199856T3 (es) | 1999-09-13 | 2004-03-01 | Boehringer Ingelheim Pharmaceuticals, Inc. | Nuevos compuestos heterociclicos, utiles como inhibidores reversibles de cisteina proteasas. |
| US6420364B1 (en) | 1999-09-13 | 2002-07-16 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compound useful as reversible inhibitors of cysteine proteases |
| US6921763B2 (en) | 1999-09-17 | 2005-07-26 | Abbott Laboratories | Pyrazolopyrimidines as therapeutic agents |
| US6699880B1 (en) | 1999-10-13 | 2004-03-02 | Banyu Pharmaceutical Co., Ltd. | Substituted imidazolidinone derivatives |
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| JPWO2002085890A1 (ja) | 2001-04-20 | 2004-08-12 | 萬有製薬株式会社 | ベンズイミダゾロン誘導体 |
| EP1395257A1 (en) | 2001-06-12 | 2004-03-10 | Elan Pharmaceuticals, Inc. | Macrocycles useful in the treatment of alzheimer's disease |
| WO2004089942A2 (en) | 2001-10-02 | 2004-10-21 | Acadia Pharmaceuticals Inc. | Benzimidazolidinone derivatives as muscarinic agents |
| GB0128378D0 (en) | 2001-11-27 | 2002-01-16 | Smithkline Beecham Plc | Novel Compounds |
| US7550459B2 (en) | 2001-12-28 | 2009-06-23 | Acadia Pharmaceuticals, Inc. | Tetrahydroquinoline analogues as muscarinic agonists |
| ES2251624T3 (es) | 2001-12-28 | 2006-05-01 | Acadia Pharmaceuticals Inc. | Analogos de la tetrahidroquinolina como los agonistas muscarinicos. |
| US20040171614A1 (en) | 2002-02-06 | 2004-09-02 | Schering-Plough Corporation | Novel gamma secretase inhibitors |
| US7256186B2 (en) | 2002-02-06 | 2007-08-14 | Schering Corporation | Gamma secretase inhibitors |
| PT1489078E (pt) | 2002-03-28 | 2010-02-24 | Mitsubishi Tanabe Pharma Corp | Derivados de benzofurano |
| JPWO2003104230A1 (ja) | 2002-06-07 | 2005-10-06 | 協和醗酵工業株式会社 | 二環性ピリミジン誘導体 |
| HK1079787A1 (zh) | 2002-07-31 | 2006-04-13 | Ranbaxy Laboratories Limited | 用作毒蕈碱受体拮抗剂的3，6-二取代的氮杂双环[3．1．0]己烷衍生物 |
| JP4711391B2 (ja) | 2002-09-30 | 2011-06-29 | ニューロサーチ、アクティーゼルスカブ | 新規１，４−ジアザビシクロアルカン誘導体及びその製造方法 |
| RU2342388C2 (ru) | 2002-11-22 | 2008-12-27 | Джапан Тобакко Инк. | Конденсированные бициклические азотсодержащие гетероциклы, обладающие dgat ингибирующим действием |
| EP1565436B1 (en) | 2002-11-27 | 2012-04-25 | Incyte Corporation | 3-aminopyrrolidine derivatives as modulators of chemokine receptors |
| WO2004069828A1 (ja) | 2003-02-04 | 2004-08-19 | Mitsubishi Pharma Corporation | ピペリジン化合物およびその医薬用途 |
| MXPA06000441A (es) | 2003-07-17 | 2006-04-05 | Astellas Pharma Inc | Derivado de 2-acilaminotiazole o sal del mismo. |
| JPWO2005037269A1 (ja) | 2003-10-21 | 2006-12-28 | 住友製薬株式会社 | 新規ピペリジン誘導体 |
| CA2554465A1 (en) | 2004-02-05 | 2005-08-25 | Schering Corporation | Piperidine derivatives useful as ccr3 antagonists |
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| US7504424B2 (en) | 2004-07-16 | 2009-03-17 | Schering Corporation | Compounds for the treatment of inflammatory disorders |
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| US7786141B2 (en) | 2004-08-19 | 2010-08-31 | Vertex Pharmaceuticals Incorporated | Dihydrospiroindene modulators of muscarinic receptors |
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| JP4774995B2 (ja) | 2005-01-12 | 2011-09-21 | アステラス製薬株式会社 | アシルアミノチアゾール誘導体を有効成分とする医薬組成物 |
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| EP1900732A4 (en) | 2005-06-24 | 2009-11-18 | Toyama Chemical Co Ltd | NEW NITROGENATED HETEROCYCLIC COMPOUND AND SALT THEREOF |
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| ES2545907T3 (es) | 2005-12-29 | 2015-09-16 | Abbvie Inc. | Inhibidores de proteína quinasa |
| KR20080098070A (ko) * | 2006-02-22 | 2008-11-06 | 버텍스 파마슈티칼스 인코포레이티드 | 무스카린성 수용체의 조절제로서의 스피로 축합된 피페리딘 |
| AU2007221214A1 (en) | 2006-02-22 | 2007-09-07 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
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| US20130012485A1 (en) | 2006-12-22 | 2013-01-10 | Baeschlin Daniel Kaspar | Organic compounds |
| WO2008117229A1 (en) | 2007-03-23 | 2008-10-02 | Ranbaxy Laboratories Limited | Muscarinic receptor antagonists |
| US8119661B2 (en) | 2007-09-11 | 2012-02-21 | Astrazeneca Ab | Piperidine derivatives and their use as muscarinic receptor modulators |
| UY31672A1 (es) | 2008-02-28 | 2009-09-30 | "agonistas de receptores muscarínicos composiciones farmacéuticas métodos de tratamiento de los mismos, y procedimientos para su preparación" | |
| WO2009118370A1 (en) | 2008-03-27 | 2009-10-01 | Janssen Pharmaceutica Nv | Aza-bicyclohexyl substituted indolyl alkyl amino derivatives as novel inhibitors of histone deacetylase |
| MX2011004340A (es) | 2008-10-29 | 2011-05-23 | Gruenenthal Gmbh | Espiroaminas sustituidas. |
| CN102256963B (zh) | 2008-12-19 | 2014-06-11 | 贝林格尔.英格海姆国际有限公司 | 作为ccr2受体拮抗剂用于治疗炎症、哮喘和copd的环状嘧啶-4-甲酰胺 |
| EP2419419B1 (en) | 2009-04-17 | 2014-12-03 | Janssen Pharmaceutica NV | 4-azetidinyl-1-phenyl-cyclohexane antagonists of ccr2 |
| FR2945531A1 (fr) | 2009-05-12 | 2010-11-19 | Sanofi Aventis | Derives de 7-aza-spiro°3,5!nonane-7-carboxylates, leur preparation et leur application en therapeutique |
| WO2011112825A2 (en) | 2010-03-10 | 2011-09-15 | Vanderbilt University | Heterocyclyl-azabicyclo[3.2.1]octane analogs as selective m1 agonists and methods of making and using same |
| US8822447B2 (en) | 2010-04-22 | 2014-09-02 | Janssen Pharmaceutica Nv | Indazole compounds useful as ketohexokinase inhibitors |
| EP2563127A4 (en) | 2010-04-27 | 2013-11-06 | Merck Sharp & Dohme | PROLYLCARBOXYPEPTIDASE INHIBITORS |
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| JP2013528180A (ja) | 2010-05-28 | 2013-07-08 | ジーイー・ヘルスケア・リミテッド | 放射性標識化合物及びその製造方法 |
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| EP2780015B1 (en) | 2011-11-18 | 2017-01-04 | Heptares Therapeutics Limited | Muscarinic m1 receptor agonists |
| CN107098899B (zh) | 2012-09-18 | 2019-09-06 | 赫普泰雅治疗有限公司 | 作为毒蕈碱的m1受体激动剂的二环氮杂化合物 |
| JP6478923B2 (ja) | 2013-02-07 | 2019-03-06 | ヘプタレス セラピューティクス リミテッドＨｅｐｔａｒｅｓ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｌｉｍｉｔｅｄ | ムスカリンｍ４受容体アゴニストとしてのピペリジン−１−イル及びアゼピン−１−イルカルボキシレート |
| SG11201606269WA (en) | 2014-02-06 | 2016-09-29 | Heptares Therapeutics Ltd | Bicyclic aza compounds as muscarinic m1 receptor and/or m4 receptor agonists |
| GB201404922D0 (en) | 2014-03-19 | 2014-04-30 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| SG11201706501VA (en) | 2015-02-13 | 2017-09-28 | Suven Life Sciences Ltd | AMIDE COMPOUNDS AS 5-HT<sb>4</sb> RECEPTOR AGONISTS |
| GB201504675D0 (en) * | 2015-03-19 | 2015-05-06 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201513740D0 (en) | 2015-08-03 | 2015-09-16 | Heptares Therapeutics Ltd | Muscarinic agonist |
| GB201513743D0 (en) | 2015-08-03 | 2015-09-16 | Heptares Therapeutics Ltd | Muscarinic agonists |
| GB201513742D0 (en) | 2015-08-03 | 2015-09-16 | Heptares Therapeutics Ltd | Muscarinic agonists |
| GB201519352D0 (en) | 2015-11-02 | 2015-12-16 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201617454D0 (en) | 2016-10-14 | 2016-11-30 | Heptares Therapeutics Limited | Pharmaceutical compounds |
| US10259787B2 (en) | 2016-10-14 | 2019-04-16 | Heptares Therapeutics Limited | Substituted cyclohexanes as muscarinic M1 receptor and/or M4 receptor agonists |
| GB201709652D0 (en) | 2017-06-16 | 2017-08-02 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| US10501483B2 (en) | 2017-10-24 | 2019-12-10 | Allergan, Inc. | Enamines and diastereo-selective reduction of enamines |
| GB201810239D0 (en) | 2018-06-22 | 2018-08-08 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201810245D0 (en) | 2018-06-22 | 2018-08-08 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201819961D0 (en) | 2018-12-07 | 2019-01-23 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201819960D0 (en) | 2018-12-07 | 2019-01-23 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB202020191D0 (en) | 2020-12-18 | 2021-02-03 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB202103211D0 (en) | 2021-03-08 | 2021-04-21 | Heptares Therapeutics Ltd | Pharmaceutical compounds for use in therapy |
-
2015
- 2015-08-03 GB GBGB1513743.3A patent/GB201513743D0/en not_active Ceased
-
2016
- 2016-08-03 JP JP2018504992A patent/JP6843114B2/ja active Active
- 2016-08-03 AU AU2016304387A patent/AU2016304387B2/en active Active
- 2016-08-03 US US15/749,957 patent/US10738029B2/en active Active
- 2016-08-03 CA CA2994203A patent/CA2994203C/en active Active
- 2016-08-03 ES ES16750222T patent/ES2894637T3/es active Active
- 2016-08-03 CN CN201680045224.1A patent/CN108025004B/zh active Active
- 2016-08-03 WO PCT/GB2016/052385 patent/WO2017021729A1/en not_active Ceased
- 2016-08-03 DK DK16750222.8T patent/DK3331529T3/da active
- 2016-08-03 EP EP16750222.8A patent/EP3331529B1/en active Active
-
2020
- 2020-07-29 US US16/942,167 patent/US11254656B2/en active Active
-
2022
- 2022-02-15 US US17/672,302 patent/US12024499B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN108025004A (zh) | 2018-05-11 |
| CA2994203C (en) | 2023-11-28 |
| US20200354339A1 (en) | 2020-11-12 |
| US11254656B2 (en) | 2022-02-22 |
| AU2016304387B2 (en) | 2020-10-22 |
| JP2018522033A (ja) | 2018-08-09 |
| HK1250138A1 (en) | 2018-11-30 |
| AU2016304387A1 (en) | 2018-02-22 |
| EP3331529A1 (en) | 2018-06-13 |
| DK3331529T3 (da) | 2021-10-18 |
| US10738029B2 (en) | 2020-08-11 |
| US20230002354A1 (en) | 2023-01-05 |
| US20180222885A1 (en) | 2018-08-09 |
| US12024499B2 (en) | 2024-07-02 |
| WO2017021729A1 (en) | 2017-02-09 |
| CN108025004B (zh) | 2021-07-09 |
| CA2994203A1 (en) | 2017-02-09 |
| ES2894637T3 (es) | 2022-02-15 |
| EP3331529B1 (en) | 2021-09-29 |
| GB201513743D0 (en) | 2015-09-16 |
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