JP6631616B2 - ＣＤＫ阻害剤としての２−アミノ−ピリド［２，３−ｄ］ピリミジン−７（８Ｈ）−オン誘導体及びその使用 - Google Patents
ＣＤＫ阻害剤としての２−アミノ−ピリド［２，３−ｄ］ピリミジン−７（８Ｈ）−オン誘導体及びその使用 Download PDFInfo
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- JP6631616B2 JP6631616B2 JP2017504046A JP2017504046A JP6631616B2 JP 6631616 B2 JP6631616 B2 JP 6631616B2 JP 2017504046 A JP2017504046 A JP 2017504046A JP 2017504046 A JP2017504046 A JP 2017504046A JP 6631616 B2 JP6631616 B2 JP 6631616B2
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Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2655645T3 (es) | 2011-07-29 | 2018-02-21 | Karyopharm Therapeutics, Inc. | Moduladores de transporte nuclear que contienen hidrazida y usos de los mismos |
| PL3404027T3 (pl) | 2012-05-09 | 2020-09-21 | Biogen Ma Inc. | Modulatory transportu jądrowego i ich zastosowania |
| LT3010892T (lt) | 2013-06-21 | 2019-04-10 | Karyopharm Therapeutics Inc. | 1,2,4-triazolai kaip branduolio transporto moduliatoriai ir jų panaudojimas |
| DK3180331T3 (da) * | 2014-08-15 | 2022-09-12 | Karyopharm Therapeutics Inc | Polymorfer af selinexor |
| CN105130986B (zh) * | 2015-09-30 | 2017-07-18 | 广州科擎新药开发有限公司 | 嘧啶或吡啶并吡啶酮类化合物及其应用 |
| EP3386981B1 (en) * | 2015-12-13 | 2021-10-13 | Hangzhou Innogate Pharma Co., Ltd. | Heterocycles useful as anti-cancer agents |
| EP3397633A1 (en) | 2015-12-31 | 2018-11-07 | Karyopharm Therapeutics, Inc. | Nuclear transport modulators and uses thereof |
| MA43530A (fr) | 2015-12-31 | 2018-11-07 | Karyopharm Therapeutics Inc | Modulateurs de transport nucléaire et leurs utilisations |
| US11077110B2 (en) | 2016-03-18 | 2021-08-03 | Tufts Medical Center | Compositions and methods for treating and preventing metabolic disorders |
| US10449195B2 (en) | 2016-03-29 | 2019-10-22 | Shenzhen Pharmacin Co., Ltd. | Pharmaceutical formulation of palbociclib and a preparation method thereof |
| CN105777749A (zh) * | 2016-04-06 | 2016-07-20 | 中国药科大学 | 吡啶并嘧啶类化合物、其制备方法及其用途 |
| CN105968109B (zh) * | 2016-05-13 | 2017-11-17 | 聂红梅 | 一种制备帕博西尼中间体的方法 |
| JP2019516767A (ja) * | 2016-05-23 | 2019-06-20 | イーライ リリー アンド カンパニー | 癌の治療のためのペンブロリズマブとアベマシクリブとの組合せ |
| CN106083844B (zh) * | 2016-06-05 | 2017-11-10 | 陈志明 | 一种制备抗乳腺癌药物帕博西尼中间体的方法 |
| WO2018001270A1 (en) * | 2016-06-30 | 2018-01-04 | Noratech Pharmaceuticals, Inc. | Palbociclib prodrugs and composition thereof |
| WO2020036993A1 (en) * | 2018-08-15 | 2020-02-20 | Aiviva Biopharma, Inc. | Multi-kinase inhibitors of vegf and tgf beta and uses thereof |
| BR112019005526A2 (pt) | 2016-10-20 | 2019-06-18 | Pfizer | agentes antiproliferativos para tratamento de pah |
| EP3541389A1 (en) * | 2016-11-16 | 2019-09-25 | Pfizer Inc | Combination of an egfr t790m inhibitor and a cdk inhibitor for the treatment of non-small cell lung cancer |
| WO2018098472A1 (en) | 2016-11-28 | 2018-05-31 | Karyopharm Therapeutics Inc. | Crm1 inhibitors for treating epilepsy |
| SI3546458T1 (sl) | 2016-11-28 | 2021-03-31 | Teijin Pharma Limited | Derivati ((piridin-2-il)-amino)pirido(3,4-d)pirimidina in ((piridazin-3-il)amino)pirido(3,4-d)pirimidina kot zaviralci CDK4/6 za zdravljenje npr. revmatoidnega artritisa, arterioskleroze, pljučne fibroze, možganske kapi ali raka |
| IL267299B (en) * | 2016-12-16 | 2022-09-01 | Cstone Pharmaceuticals | Cdk4/6 inhibitor |
| AU2018209164B2 (en) | 2017-01-17 | 2021-11-04 | Heparegenix Gmbh | Protein kinase inhibitors for promoting liver regeneration or reducing or preventing hepatocyte death |
| US20190388407A1 (en) | 2017-02-12 | 2019-12-26 | Aiviva Biopharma, Inc. | Multikinase inhibitors of vegf and tfg beta and uses thereof |
| CN108929324A (zh) * | 2017-05-22 | 2018-12-04 | 南开大学 | 新型1,1-环丙基二酰胺衍生物的制备与应用 |
| KR102557834B1 (ko) * | 2017-06-07 | 2023-07-21 | 프레시전 인코포레이티드 | 신규의 세포 태그의 발현 |
| CN109384767B (zh) * | 2017-08-08 | 2020-05-05 | 江苏恒瑞医药股份有限公司 | 一种吡啶并嘧啶类衍生物的制备方法及其中间体 |
| CN109394767A (zh) * | 2017-12-19 | 2019-03-01 | 清华大学 | 化合物在制备药物中的用途 |
| CA3089592A1 (en) | 2018-02-15 | 2019-08-22 | Nuvation Bio Inc. | Heterocyclic compounds as kinase inhibitors |
| EP3786161A4 (en) | 2018-04-24 | 2021-05-05 | Shanghai Haiyan Pharmaceutical Technology Co., Ltd | CDK4 / 6 INHIBITOR, PHARMACEUTICALLY ACCEPTABLE SALT, POLYMORPHIC OF THEM AND ASSOCIATED USE |
| CN110496223B (zh) * | 2018-05-17 | 2021-09-10 | 复旦大学附属肿瘤医院 | 一种治疗非霍奇金氏淋巴瘤的药物组合物 |
| CN108524938B (zh) * | 2018-06-15 | 2020-06-19 | 深圳大学 | Cdk6小分子抑制剂在降低肝癌细胞对抗肿瘤药或放疗的耐受性中的应用 |
| WO2020006210A1 (en) * | 2018-06-27 | 2020-01-02 | Tufts Medical Center, Inc. | Pyridopyrimidine compounds and methods of their use |
| AU2019310595B2 (en) | 2018-07-27 | 2022-11-24 | 1200 Pharma Llc | CDK inhibitors and uses thereof |
| WO2020108590A1 (zh) * | 2018-11-30 | 2020-06-04 | 上海拓界生物医药科技有限公司 | 嘧啶并五元氮杂环类衍生物、其制备方法及其在医药上的应用 |
| WO2020114519A1 (zh) * | 2018-12-07 | 2020-06-11 | 杭州英创医药科技有限公司 | 作为cdk-hdac双通路抑制剂的杂环化合物 |
| DK3930715T3 (da) * | 2019-02-27 | 2024-08-05 | Astrazeneca Ab | Saracatinib til anvendelse til behandling af idiopatisk lungefibrose |
| CN114306245A (zh) | 2020-09-29 | 2022-04-12 | 深圳市药欣生物科技有限公司 | 无定形固体分散体的药物组合物及其制备方法 |
| TW202237585A (zh) | 2020-11-27 | 2022-10-01 | 瑞士商瑞森製藥公司 | Ｃｄｋ抑制劑 |
| WO2022149057A1 (en) | 2021-01-05 | 2022-07-14 | Rhizen Pharmaceuticals Ag | Cdk inhibitors |
| CN114907339B (zh) * | 2021-02-08 | 2023-07-14 | 成都奥睿药业有限公司 | 4-（4-氨基苯氧基）吡啶-2-胺衍生物及其用途 |
| US12084453B2 (en) | 2021-12-10 | 2024-09-10 | Incyte Corporation | Bicyclic amines as CDK12 inhibitors |
| CN114306255B (zh) * | 2021-12-30 | 2023-05-23 | 北京鑫开元医药科技有限公司 | 一种甲基酮类衍生物药物制剂及其制备方法 |
| PE20242008A1 (es) | 2021-12-30 | 2024-10-03 | Biomea Fusion Inc | Compuestos de pirazina como inhibidores de flt3 |
| AU2023289896A1 (en) * | 2022-06-22 | 2024-12-05 | Nikang Therapeutics, Inc. | Bifunctional compounds containing pyrido[2,3-djpyrimidin-7(8h)-one derivatives for degrading cyclin-dependent kinase 2 via ubiquitin proteasome pathway |
| WO2024107730A1 (en) * | 2022-11-14 | 2024-05-23 | Onconova Therapeutics, Inc. | Methods and compositions for treating cancer |
| WO2024173833A1 (en) * | 2023-02-16 | 2024-08-22 | Mei Pharma, Inc. | Combination of a cdk inhibitor and a flt3 inhibitor for the treatment of cancer |
| TW202508595A (zh) | 2023-05-04 | 2025-03-01 | 美商銳新醫藥公司 | 用於ｒａｓ相關疾病或病症之組合療法 |
| WO2025034702A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Rmc-6291 for use in the treatment of ras protein-related disease or disorder |
| WO2025080946A2 (en) | 2023-10-12 | 2025-04-17 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025217307A1 (en) | 2024-04-09 | 2025-10-16 | Revolution Medicines, Inc. | Methods for predicting response to a ras(on) inhibitor and combination therapies |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
Family Cites Families (68)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5620981A (en) | 1995-05-03 | 1997-04-15 | Warner-Lambert Company | Pyrido [2,3-D]pyrimidines for inhibiting protein tyrosine kinase mediated cellular proliferation |
| US6498163B1 (en) | 1997-02-05 | 2002-12-24 | Warner-Lambert Company | Pyrido[2,3-D]pyrimidines and 4-aminopyrimidines as inhibitors of cellular proliferation |
| EA004436B1 (ru) | 1998-09-29 | 2004-04-29 | Уайт Холдингз Корпорейшн | Замещенные 3-цианохинолины в качестве ингибиторов протеинтирозинкиназ |
| US6534535B1 (en) | 1999-08-12 | 2003-03-18 | Millennium Pharmaceuticals, Inc. | Inhibitors of factor Xa |
| JP4411709B2 (ja) | 1999-11-02 | 2010-02-10 | 凸版印刷株式会社 | キノロン誘導体ならびにそれを使用した有機ｅｌ素子 |
| WO2001044257A1 (en) | 1999-12-17 | 2001-06-21 | Ariad Pharmaceuticals, Inc. | Proton pump inhibitors |
| EP1255741A2 (en) | 2000-02-01 | 2002-11-13 | Cor Therapeutics, Inc. | 2- 1H]-QUINOLONE AND 2- 1H]-QUINOXALONE INHIBITORS OF FACTOR Xa |
| KR20020075805A (ko) * | 2000-03-06 | 2002-10-05 | 워너-램버트 캄파니 | 5-알킬피리도[2,3-ｄ]피리미딘 타이로신 카이나제 억제제 |
| MXPA02011263A (es) | 2000-08-04 | 2003-03-10 | Warner Lambert Co | 2-(4-piridil)amino-6-dialcoxifenil- pirido(2,3-d) pirimidin-7-onas. |
| US6506749B2 (en) | 2000-08-31 | 2003-01-14 | Syntex (U.S.A.) Llc | 7-oxo-pyridopyrimidines (I) |
| CA2356544C (en) | 2000-10-03 | 2006-04-04 | Warner-Lambert Company | Pyridotriazines and pyridopyridazines |
| AU2002256615B2 (en) | 2001-02-12 | 2007-09-13 | F. Hoffmann-La Roche Ag | 6-substituted pyrido-pyrimidines |
| PE20030008A1 (es) | 2001-06-19 | 2003-01-22 | Bristol Myers Squibb Co | Inhibidores duales de pde 7 y pde 4 |
| KR20060111716A (ko) * | 2002-01-22 | 2006-10-27 | 워너-램버트 캄파니 엘엘씨 | 2-(피리딘-2-일아미노)-피리도[2,3-ｄ]피리미딘-7-온 |
| PA8577501A1 (es) | 2002-07-25 | 2004-02-07 | Warner Lambert Co | Inhibidores de quinasas |
| US20050009849A1 (en) | 2003-01-03 | 2005-01-13 | Veach Darren R. | Pyridopyrimidine kinase inhibitors |
| MXPA05007503A (es) | 2003-01-17 | 2005-09-21 | Warner Lambert Co | Heterociclicos 2-aminopiridina sustituidos como inhibidores de proliferacion celular. |
| PL1648889T3 (pl) * | 2003-07-11 | 2009-03-31 | Warner Lambert Co | Sól izetionian selektywnego inhibitora CDK4 |
| CN1863774B (zh) | 2003-10-08 | 2010-12-15 | Irm责任有限公司 | 用作蛋白激酶抑制剂的化合物和组合物 |
| BRPI0507852A (pt) | 2004-02-18 | 2007-07-10 | Warner Lambert Co | 2-(piridin-3-ilamino)-pirido[2,3-d]pirimidin-7-onas |
| WO2005105801A1 (en) | 2004-05-04 | 2005-11-10 | Warner-Lambert Company Llc | Pyrrolyl substituted pyrido[2,3-d]pyrimidin-7-ones and derivatives thereof as therapeutic agents |
| WO2006021547A1 (de) | 2004-08-26 | 2006-03-02 | Boehringer Ingelheim International Gmbh | Pteridinone als plk (polo like kinase) inhibitoren |
| WO2006056863A1 (en) | 2004-11-23 | 2006-06-01 | Ranbaxy Laboratories Limited | Pyrido’2, 3-d!pyrimidines as anti-inflammatory agents |
| US20060142312A1 (en) | 2004-12-23 | 2006-06-29 | Pfizer Inc | C6-aryl and heteroaryl substituted pyrido[2,3-D] pyrimidin-7-ones |
| EP1844023A1 (en) | 2004-12-31 | 2007-10-17 | Sk Chemicals Co., Ltd. | Quinazoline derivatives for the treatment and prevention of diabetes and obesity |
| US20090036472A1 (en) | 2005-02-02 | 2009-02-05 | Palle Venkata P | Azabicyclo derivatives as anti-inflammatory agents |
| CN102746298A (zh) | 2005-10-07 | 2012-10-24 | 埃克塞里艾克西斯公司 | PI3Kα的吡啶并嘧啶酮抑制剂 |
| FR2896246B1 (fr) | 2006-01-13 | 2008-08-15 | Sanofi Aventis Sa | Derives de pyrido-pyrimidone, leur preparation, leur application en therapeutique. |
| WO2007125405A2 (en) | 2006-05-01 | 2007-11-08 | Pfizer Products Inc. | Substituted 2-amino-fused heterocyclic compounds |
| BRPI0711628A2 (pt) | 2006-05-15 | 2011-12-06 | Irm Llc | composto, composição farmacêutica, uso e processo para preparação do composto |
| WO2008032162A1 (en) | 2006-09-15 | 2008-03-20 | Pfizer Products Inc. | Pyrido (2, 3-d) pyrimidin0ne compounds and their use as pi3 inhibitors |
| EP1914234A1 (en) | 2006-10-16 | 2008-04-23 | GPC Biotech Inc. | Pyrido[2,3-d]pyrimidines and their use as kinase inhibitors |
| CA2668731A1 (en) | 2006-11-09 | 2008-05-15 | Tobias Gabriel | Kinase inhibitors and methods for using the same |
| AU2008239655B2 (en) | 2007-04-11 | 2013-06-20 | Exelixis, Inc. | Pyrido (2, 3-d) pyrimidin-7-one compounds as inhibitors of PI3k-alpha for the treatment of cancer |
| WO2008157500A1 (en) | 2007-06-17 | 2008-12-24 | Kalypsys, Inc. | Aminoquinazoline cannabinoid receptor modulators for treatment of disease |
| JP5302389B2 (ja) | 2008-04-29 | 2013-10-02 | エフ．ホフマン−ラ ロシュ アーゲー | Ｊｎｋのピリミジニルピリドンインヒビター |
| CN101747306B (zh) | 2008-11-28 | 2012-08-29 | 中国中化股份有限公司 | 取代醚类化合物及其应用 |
| US20120100100A1 (en) * | 2009-05-13 | 2012-04-26 | Sharpless Norman E | Cyclin dependent kinase inhibitors and methods of use |
| WO2011044535A2 (en) | 2009-10-09 | 2011-04-14 | Afraxis, Inc. | 8-ethyl-6-(aryl)pyrido[2,3-d]pyrimidin-7(8h)-ones for the treatment of cns disorders |
| KR101754664B1 (ko) | 2009-12-18 | 2017-07-06 | 템플 유니버시티-오브 더 커먼웰쓰 시스템 오브 하이어 에듀케이션 | 치환된 피리도〔2,3-ｄ〕피리미딘-7(8ｈ)-온스 및 이의 치료 용도 |
| ES2689177T3 (es) * | 2010-04-13 | 2018-11-08 | Novartis Ag | Combinación que comprende un inhibidor de cinasa 4 dependiente de ciclina o cinasa dependiente de ciclina (CDK4/6) y un inhibidor de mTOR para tratar cáncer |
| WO2011156646A2 (en) | 2010-06-09 | 2011-12-15 | Afraxis, Inc. | 6-(sulfonylaryl)pyrido[2,3-d]pyrimidin-7(8h)-ones for the treatment of cns disorders |
| US20130231348A1 (en) | 2010-06-09 | 2013-09-05 | Afraxis, Inc. | 8-(HETEROARYLMETHYL)PYRIDO[2,3-d]PYRIMIDIN-7(8H)-ONES FOR THE TREATMENT OF CNS DISORDERS |
| EP2580216A4 (en) | 2010-06-10 | 2014-07-23 | Afraxis Holdings Inc | 8- (SULFONYLBENZYL) PYRIDO- [2,3-D-] PYRIMIDIN-7- (8H) -ONE FOR THE TREATMENT OF DISEASES OF THE CENTRAL NERVOUS SYSTEM |
| EP2580217A4 (en) | 2010-06-10 | 2014-06-18 | Afraxis Holdings Inc | 6- (ETHYNYL-) PYRIDO- [2,3-D-] PYRIMIDIN-7- (8H) -ONE FOR THE TREATMENT OF DISEASES OF THE CENTRAL NERVOUS SYSTEM |
| PL2600719T3 (pl) | 2010-08-05 | 2015-03-31 | Univ Temple | 2-Podstawione 8-alkilo-7-okso-7,8-dihydropirydo[2,3-d]pirymidyno-6-karbonitryle oraz ich zastosowania |
| ES2377610B1 (es) | 2010-09-01 | 2013-02-05 | Institut Químic de Sarriá CETS Fundació Privada | Preparación de compuestos pirido[2,3-d]pirimidin-7(8h)-ona sustituidos. |
| KR20160035613A (ko) * | 2011-03-23 | 2016-03-31 | 암젠 인크 | Cdk 4/6 및 flt3의 융합된 트리사이클릭 이중 저해제 |
| AR085958A1 (es) | 2011-04-08 | 2013-11-06 | Afraxis Inc | 8-etil-6-(aril)pirido[2,3-d]pirimidin-7(8h)-onas para el tratamiento de trastornos del cns y cancer |
| BR112014010631A2 (pt) | 2011-11-04 | 2017-04-25 | Afraxis Holdings Inc | inibidores de pak para o tratamento da síndrome do x frágil |
| DE112013002484B4 (de) | 2012-05-14 | 2023-05-04 | Shanghai Yidian Pharmaceutical Technology Development Co., Ltd. | Pteridinketon-Derivat und Anwendungen desselben als EGFR-, BLK- und FLT3-Inhibitor |
| WO2014074926A1 (en) | 2012-11-09 | 2014-05-15 | Rutgers, The State University Of New Jersey | Therapeutic hydroxyquinolones |
| CN103012399B (zh) | 2012-11-22 | 2015-06-17 | 中国科学院广州生物医药与健康研究院 | 7-氧代吡啶并嘧啶类化合物及其药用组合物和应用 |
| TW201522332A (zh) | 2013-03-01 | 2015-06-16 | Amgen Inc | 經取代之７－酮基－吡啶并［２，３－ｄ］嘧啶及其使用方法 |
| US9321786B2 (en) | 2013-03-15 | 2016-04-26 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| CA2904054A1 (en) | 2013-03-15 | 2014-09-25 | Concert Pharmaceuticals, Inc. | Deuterated palbociclib |
| JPWO2014174745A1 (ja) | 2013-04-26 | 2017-02-23 | 国立大学法人京都大学 | Ｅｇ５阻害剤 |
| US20140323478A1 (en) | 2013-04-30 | 2014-10-30 | Afraxis Holdings, Inc. | Serine/threonine kinase inhibitors |
| WO2014179498A1 (en) | 2013-04-30 | 2014-11-06 | Genentech, Inc. | Serine/threonine kinase inhibitors |
| WO2014182829A1 (en) | 2013-05-09 | 2014-11-13 | Principia Biopharma Inc. | Quinolone derivatives as fibroblast growth factor inhibitors |
| WO2014183520A1 (zh) | 2013-05-17 | 2014-11-20 | 上海恒瑞医药有限公司 | 吡啶并嘧啶类衍生物、其制备方法及其在医药上的应用 |
| EP2813504A1 (en) | 2013-06-14 | 2014-12-17 | Institut Quimic De Sarriá Cets, Fundació Privada | 4-Amino-6-(2,6-dichlorophenyl)-2-(phenylamino)-pyrido[2,3-d]pyrimidin-7(8H)-one derivatives, synthesis and uses thereof |
| WO2015011252A1 (en) | 2013-07-26 | 2015-01-29 | F. Hoffmann-La Roche Ag | Pyrimidine-pyridinone serine/threonine kinase inhibitors |
| CN104418860B (zh) | 2013-08-20 | 2016-09-07 | 中国科学院广州生物医药与健康研究院 | 嘧啶并杂环类化合物及其药用组合物和应用 |
| DK3395814T3 (da) | 2013-10-25 | 2022-07-04 | Blueprint Medicines Corp | Hæmmere af fibroblastvækstfaktorreceptoren |
| EP3076789A4 (en) | 2013-12-04 | 2017-11-22 | The Scripps Research Institute | Novel compounds as jnk kinase inhibitors |
| US9815797B2 (en) | 2013-12-09 | 2017-11-14 | Ucb Biopharma Sprl | Fused bicyclic heteroaromatic derivatives as modulators of TNF activity |
| CN106459034B (zh) | 2014-02-07 | 2018-01-12 | 普林斯匹亚生物制药公司 | 作为成纤维细胞生长因子受体抑制剂的喹诺酮衍生物 |
-
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- 2015-07-23 WO PCT/CN2015/084983 patent/WO2016015597A1/en not_active Ceased
- 2015-07-23 WO PCT/CN2015/084984 patent/WO2016015598A1/en not_active Ceased
- 2015-07-23 CA CA2954189A patent/CA2954189A1/en not_active Abandoned
- 2015-07-23 EP EP15828004.0A patent/EP3172214B1/en active Active
- 2015-07-23 CN CN201510439488.2A patent/CN105294682B/zh active Active
- 2015-07-24 CN CN201510443167.XA patent/CN105294736B/zh active Active
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| Publication number | Publication date |
|---|---|
| CA2954189A1 (en) | 2016-02-04 |
| CN105294736A (zh) | 2016-02-03 |
| EP3172214A4 (en) | 2018-02-07 |
| EP3172214B1 (en) | 2020-05-13 |
| HK1232223A1 (en) | 2018-01-05 |
| WO2016015598A1 (en) | 2016-02-04 |
| CN105294682B (zh) | 2017-07-07 |
| CN105294736B (zh) | 2020-01-14 |
| CN105294681B (zh) | 2017-07-07 |
| AU2015296322A1 (en) | 2017-01-12 |
| US9828373B2 (en) | 2017-11-28 |
| AU2015296322B2 (en) | 2019-09-19 |
| CN105294682A (zh) | 2016-02-03 |
| US20170121323A1 (en) | 2017-05-04 |
| CN105294681A (zh) | 2016-02-03 |
| JP2017524702A (ja) | 2017-08-31 |
| EP3172214A1 (en) | 2017-05-31 |
| WO2016015597A1 (en) | 2016-02-04 |
| KR20170032244A (ko) | 2017-03-22 |
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