ES2808868T3 - 2'-Cloro aminopirimidinona y nucleósidos de diona de pirimidina - Google Patents
2'-Cloro aminopirimidinona y nucleósidos de diona de pirimidina Download PDFInfo
- Publication number
- ES2808868T3 ES2808868T3 ES15760544T ES15760544T ES2808868T3 ES 2808868 T3 ES2808868 T3 ES 2808868T3 ES 15760544 T ES15760544 T ES 15760544T ES 15760544 T ES15760544 T ES 15760544T ES 2808868 T3 ES2808868 T3 ES 2808868T3
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- pharmaceutically acceptable
- acceptable salt
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- RIOQSEWOXXDEQQ-UHFFFAOYSA-O triphenylphosphanium Chemical compound C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-O 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229950008396 ulobetasol propionate Drugs 0.000 description 1
- BDSYKGHYMJNPAB-LICBFIPMSA-N ulobetasol propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]2(C)C[C@@H]1O BDSYKGHYMJNPAB-LICBFIPMSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/073—Pyrimidine radicals with 2-deoxyribosyl as the saccharide radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (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 |
|---|---|---|---|
| US201462040349P | 2014-08-21 | 2014-08-21 | |
| PCT/US2015/045849 WO2016028866A1 (en) | 2014-08-21 | 2015-08-19 | 2'-chloro aminopyrimidinone and pyrimidine dione nucleosides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2808868T3 true ES2808868T3 (es) | 2021-03-02 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES15760544T Active ES2808868T3 (es) | 2014-08-21 | 2015-08-19 | 2'-Cloro aminopirimidinona y nucleósidos de diona de pirimidina |
Country Status (17)
| Country | Link |
|---|---|
| US (6) | US9617295B2 (enExample) |
| EP (2) | EP3183261B1 (enExample) |
| JP (2) | JP6765364B2 (enExample) |
| KR (1) | KR102528928B1 (enExample) |
| CN (1) | CN106573954A (enExample) |
| AR (1) | AR101561A1 (enExample) |
| AU (1) | AU2015305593C1 (enExample) |
| BR (1) | BR112017003242A2 (enExample) |
| CA (1) | CA2958546C (enExample) |
| EA (1) | EA201790234A1 (enExample) |
| ES (1) | ES2808868T3 (enExample) |
| IL (1) | IL250426A0 (enExample) |
| MX (1) | MX2017002288A (enExample) |
| NZ (1) | NZ728707A (enExample) |
| SG (1) | SG11201700810SA (enExample) |
| TW (1) | TWI673283B (enExample) |
| WO (1) | WO2016028866A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SI2794627T1 (sl) | 2011-12-22 | 2019-02-28 | Alios Biopharma, Inc. | Substituirani nukleozidi, nukleotidi in njihovi analogi |
| USRE48171E1 (en) | 2012-03-21 | 2020-08-25 | Janssen Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| US9441007B2 (en) | 2012-03-21 | 2016-09-13 | Alios Biopharma, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| TWI673283B (zh) * | 2014-08-21 | 2019-10-01 | 美商基利科學股份有限公司 | ２’－氯胺基嘧啶酮及嘧啶二酮核苷類 |
| PE20170698A1 (es) * | 2014-09-26 | 2017-06-05 | Riboscience Llc | Derivados de nucleosidos sustituidos con 4'-vinilo como inhibidores de la replicacion del arn del virus respiratorio sincitial |
| CN118286245A (zh) | 2014-12-26 | 2024-07-05 | 埃莫里大学 | N4-羟基胞苷和衍生物及与其相关的抗病毒用途 |
| WO2018009623A1 (en) * | 2016-07-08 | 2018-01-11 | Atea Pharmaceuticals, Inc. | β-D-2'-DEOXY-2'-SUBSTITUTED-4'-SUBSTITUTED-2-SUBSTITUTED-N6-SUBSTITUTED-6-AMINOPURINE NUCLEOTIDES FOR THE TREATMENT OF PARAMYXOVIRUS AND ORTHOMYXOVIRUS INFECTIONS |
| RS66222B1 (sr) | 2017-12-07 | 2024-12-31 | Univ Emory | N4-hidroksicitidin i derivati i antivirusne upotrebe povezane sa njim |
| US20250009777A1 (en) * | 2021-11-12 | 2025-01-09 | National University Corporation Hokkaido University | Antiviral agent |
| TW202400134A (zh) | 2022-03-15 | 2024-01-01 | 美商羅米醫療公司 | 用於治療疾病之化合物及方法 |
| WO2024016639A1 (zh) * | 2022-07-21 | 2024-01-25 | 华创合成制药股份有限公司 | 一种抗病毒感染的化合物及其制备方法和用途 |
Family Cites Families (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3361306A (en) | 1966-03-31 | 1968-01-02 | Merck & Co Inc | Aerosol unit dispensing uniform amounts of a medically active ingredient |
| US3565070A (en) | 1969-02-28 | 1971-02-23 | Riker Laboratories Inc | Inhalation actuable aerosol dispenser |
| FR2224175B1 (enExample) | 1973-04-04 | 1978-04-14 | Isf Spa | |
| US4069819A (en) | 1973-04-13 | 1978-01-24 | Societa Farmaceutici S.P.A. | Inhalation device |
| IT1017153B (it) | 1974-07-15 | 1977-07-20 | Isf Spa | Apparecchio per inalazioni |
| SE438261B (sv) | 1981-07-08 | 1985-04-15 | Draco Ab | Anvendning i dosinhalator av ett perforerat membran |
| US4805811A (en) | 1985-03-29 | 1989-02-21 | Aktiebolaget Draco | Dosage device |
| SE448277B (sv) | 1985-04-12 | 1987-02-09 | Draco Ab | Indikeringsanordning vid en doseringsanordning for lekemedel |
| IT1228459B (it) | 1989-02-23 | 1991-06-19 | Phidea S R L | Inalatore con svuotamento regolare e completo della capsula. |
| US4955371A (en) | 1989-05-08 | 1990-09-11 | Transtech Scientific, Inc. | Disposable inhalation activated, aerosol device for pulmonary medicine |
| CA2112674C (en) | 1991-07-02 | 2005-10-04 | John S. Patton | Method and device for delivering aerosolized medicaments |
| US5261538A (en) | 1992-04-21 | 1993-11-16 | Glaxo Inc. | Aerosol testing method |
| US5785049A (en) | 1994-09-21 | 1998-07-28 | Inhale Therapeutic Systems | Method and apparatus for dispersion of dry powder medicaments |
| US5388572A (en) | 1993-10-26 | 1995-02-14 | Tenax Corporation (A Connecticut Corp.) | Dry powder medicament inhalator having an inhalation-activated piston to aerosolize dose and deliver same |
| US5522385A (en) | 1994-09-27 | 1996-06-04 | Aradigm Corporation | Dynamic particle size control for aerosolized drug delivery |
| US5544647A (en) | 1994-11-29 | 1996-08-13 | Iep Group, Inc. | Metered dose inhalator |
| US5622163A (en) | 1994-11-29 | 1997-04-22 | Iep Group, Inc. | Counter for fluid dispensers |
| US6116234A (en) | 1999-02-01 | 2000-09-12 | Iep Pharmaceutical Devices Inc. | Metered dose inhaler agitator |
| EP1411954B1 (en) | 2000-10-18 | 2010-12-15 | Pharmasset, Inc. | Modified nucleosides for treatment of viral infections and abnormal cellular proliferation |
| EP2114980B1 (en) | 2007-01-12 | 2012-06-27 | BioCryst Pharmaceuticals, Inc. | Antiviral nucleoside analogs |
| EP2155758B1 (en) | 2007-05-10 | 2012-08-22 | Biocryst Pharmaceuticals, Inc. | Tetrahydrofuro[3,4-d]dioxolane compounds for use in the treatment of viral infections and cancer |
| CN102046626A (zh) | 2008-04-23 | 2011-05-04 | 吉里德科学公司 | 用于抗病毒治疗的carba-核苷类似物 |
| EP2313102A2 (en) | 2008-07-03 | 2011-04-27 | Biota Scientific Management | Bycyclic nucleosides and nucleotides as therapeutic agents |
| DK2480559T3 (da) | 2009-09-21 | 2013-08-05 | Gilead Sciences Inc | Fremgangsmåder og mellemprodukter til fremstillingen af 1'-cyano-carbanukleosid-analoger |
| US8455451B2 (en) | 2009-09-21 | 2013-06-04 | Gilead Sciences, Inc. | 2'-fluoro substituted carba-nucleoside analogs for antiviral treatment |
| KR20180006499A (ko) | 2009-09-21 | 2018-01-17 | 길리애드 사이언시즈, 인코포레이티드 | 항바이러스 치료용 ２'―플루오로 치환된 카바-뉴클레오사이드 유사체 |
| TW201201815A (en) | 2010-05-28 | 2012-01-16 | Gilead Sciences Inc | 1'-substituted-carba-nucleoside prodrugs for antiviral treatment |
| PH12013500033A1 (en) | 2010-07-19 | 2017-07-26 | Gilead Sciences Inc | Methods for the preparation of diasteromerically pure phosphoramidate prodrugs |
| MA34470B1 (fr) | 2010-07-22 | 2013-08-01 | Gilead Sciences Inc | Procédés et composés pour traiter des infections à virus paramyxoviridae |
| TW201305185A (zh) | 2010-09-13 | 2013-02-01 | Gilead Sciences Inc | 用於抗病毒治療之２’－氟取代之碳－核苷類似物 |
| AU2011305652B2 (en) * | 2010-09-22 | 2016-10-20 | Janssen Biopharma, Inc. | Azido nucleosides and nucleotide analogs |
| TW201306841A (zh) | 2010-12-20 | 2013-02-16 | Gilead Sciences Inc | 治療ｃ型肝炎病毒（ｈｃｖ）之方法 |
| WO2012142075A1 (en) | 2011-04-13 | 2012-10-18 | Merck Sharp & Dohme Corp. | 2'-azido substituted nucleoside derivatives and methods of use thereof for the treatment of viral diseases |
| SI2794627T1 (sl) * | 2011-12-22 | 2019-02-28 | Alios Biopharma, Inc. | Substituirani nukleozidi, nukleotidi in njihovi analogi |
| ME03502B (me) * | 2012-03-21 | 2020-04-20 | Janssen Biopharma Inc | Supstituisani nukleozidi, nukleotidi i njihovi analozi |
| GB201220843D0 (en) * | 2012-11-20 | 2013-01-02 | Univ College Cork Nat Univ Ie | Compound |
| US10034893B2 (en) * | 2013-02-01 | 2018-07-31 | Enanta Pharmaceuticals, Inc. | 5, 6-D2 uridine nucleoside/tide derivatives |
| EP3013340B9 (en) * | 2013-06-26 | 2023-10-04 | Janssen Pharmaceuticals, Inc. | Substituted nucleosides, nucleotides and analogs thereof |
| JP6562908B2 (ja) * | 2013-10-11 | 2019-08-21 | ヤンセン バイオファーマ インク． | 置換ヌクレオシド、置換ヌクレオチドおよびその類似体 |
| TWI673283B (zh) * | 2014-08-21 | 2019-10-01 | 美商基利科學股份有限公司 | ２’－氯胺基嘧啶酮及嘧啶二酮核苷類 |
-
2015
- 2015-08-07 TW TW104125796A patent/TWI673283B/zh active
- 2015-08-14 AR ARP150102625A patent/AR101561A1/es unknown
- 2015-08-19 JP JP2017508531A patent/JP6765364B2/ja active Active
- 2015-08-19 AU AU2015305593A patent/AU2015305593C1/en active Active
- 2015-08-19 SG SG11201700810SA patent/SG11201700810SA/en unknown
- 2015-08-19 ES ES15760544T patent/ES2808868T3/es active Active
- 2015-08-19 NZ NZ728707A patent/NZ728707A/en unknown
- 2015-08-19 CN CN201580044979.5A patent/CN106573954A/zh active Pending
- 2015-08-19 WO PCT/US2015/045849 patent/WO2016028866A1/en not_active Ceased
- 2015-08-19 KR KR1020177006312A patent/KR102528928B1/ko active Active
- 2015-08-19 CA CA2958546A patent/CA2958546C/en active Active
- 2015-08-19 EA EA201790234A patent/EA201790234A1/ru unknown
- 2015-08-19 EP EP15760544.5A patent/EP3183261B1/en active Active
- 2015-08-19 US US14/830,121 patent/US9617295B2/en active Active
- 2015-08-19 BR BR112017003242A patent/BR112017003242A2/pt not_active Application Discontinuation
- 2015-08-19 MX MX2017002288A patent/MX2017002288A/es unknown
- 2015-08-19 EP EP20180058.8A patent/EP3738969A1/en active Pending
-
2017
- 2017-02-02 IL IL250426A patent/IL250426A0/en unknown
- 2017-02-24 US US15/441,561 patent/US9982006B2/en active Active
-
2018
- 2018-04-11 US US15/950,442 patent/US20180340004A1/en not_active Abandoned
- 2018-12-06 US US16/212,374 patent/US20190202852A1/en not_active Abandoned
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2019
- 2019-06-27 US US16/454,536 patent/US20200157137A1/en not_active Abandoned
- 2019-09-10 US US16/565,888 patent/US20200087337A1/en not_active Abandoned
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2020
- 2020-04-10 JP JP2020070958A patent/JP2020111608A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| JP2017525699A (ja) | 2017-09-07 |
| AU2015305593A1 (en) | 2017-02-23 |
| KR20170042643A (ko) | 2017-04-19 |
| NZ728707A (en) | 2018-06-29 |
| AU2015305593B2 (en) | 2018-05-17 |
| AR101561A1 (es) | 2016-12-28 |
| TWI673283B (zh) | 2019-10-01 |
| CA2958546A1 (en) | 2016-02-25 |
| JP2020111608A (ja) | 2020-07-27 |
| TW201619178A (zh) | 2016-06-01 |
| KR102528928B1 (ko) | 2023-05-08 |
| IL250426A0 (en) | 2017-03-30 |
| BR112017003242A2 (pt) | 2017-11-28 |
| US20190202852A1 (en) | 2019-07-04 |
| US20200157137A1 (en) | 2020-05-21 |
| JP6765364B2 (ja) | 2020-10-07 |
| US9617295B2 (en) | 2017-04-11 |
| US20200087337A1 (en) | 2020-03-19 |
| WO2016028866A1 (en) | 2016-02-25 |
| CN106573954A (zh) | 2017-04-19 |
| CA2958546C (en) | 2020-06-23 |
| EP3738969A1 (en) | 2020-11-18 |
| EP3183261A1 (en) | 2017-06-28 |
| EP3183261B1 (en) | 2020-06-17 |
| US20160052953A1 (en) | 2016-02-25 |
| US20180340004A1 (en) | 2018-11-29 |
| EA201790234A1 (ru) | 2017-07-31 |
| US9982006B2 (en) | 2018-05-29 |
| SG11201700810SA (en) | 2017-03-30 |
| AU2015305593C1 (en) | 2018-11-15 |
| US20170327526A1 (en) | 2017-11-16 |
| MX2017002288A (es) | 2017-05-22 |
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