ZA201900156B - Phosphoramidates for the treatment of hepatitis b virus - Google Patents
Phosphoramidates for the treatment of hepatitis b virusInfo
- Publication number
- ZA201900156B ZA201900156B ZA2019/00156A ZA201900156A ZA201900156B ZA 201900156 B ZA201900156 B ZA 201900156B ZA 2019/00156 A ZA2019/00156 A ZA 2019/00156A ZA 201900156 A ZA201900156 A ZA 201900156A ZA 201900156 B ZA201900156 B ZA 201900156B
- Authority
- ZA
- South Africa
- Prior art keywords
- phosphoramidates
- hepatitis
- virus
- treatment
- Prior art date
Links
- 241000700721 Hepatitis B virus Species 0.000 title 1
- 150000008298 phosphoramidates Chemical class 0.000 title 1
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
- A61K31/70—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
-
- 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
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- 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
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P31/20—Antivirals for DNA viruses
-
- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Virology (AREA)
- Biotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dispersion Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662354471P | 2016-06-24 | 2016-06-24 | |
| PCT/US2017/038963 WO2017223421A1 (en) | 2016-06-24 | 2017-06-23 | Phosphoramidates for the treatment of hepatitis b virus |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA201900156B true ZA201900156B (en) | 2019-08-28 |
Family
ID=60783488
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA2019/00156A ZA201900156B (en) | 2016-06-24 | 2019-01-09 | Phosphoramidates for the treatment of hepatitis b virus |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US11364257B2 (enExample) |
| EP (1) | EP3474863A4 (enExample) |
| JP (2) | JP2019525905A (enExample) |
| KR (1) | KR20190057277A (enExample) |
| CN (1) | CN109689065A (enExample) |
| AU (1) | AU2017281531A1 (enExample) |
| BR (1) | BR112018076913A2 (enExample) |
| CA (1) | CA3029315A1 (enExample) |
| EA (1) | EA201990059A1 (enExample) |
| IL (1) | IL263859B2 (enExample) |
| PH (1) | PH12018550207A1 (enExample) |
| SG (1) | SG11201811316YA (enExample) |
| WO (1) | WO2017223421A1 (enExample) |
| ZA (1) | ZA201900156B (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3233878B1 (en) * | 2014-12-15 | 2025-09-03 | Emory University | Phosphoramidates for the treatment of hepatitis b virus |
| CN111836818B (zh) | 2018-01-10 | 2023-10-31 | 纽科利制药公司 | 氨基磷(膦)酸缩醛和磷(膦)酸缩醛化合物 |
| BR112020020804A2 (pt) | 2018-04-12 | 2021-01-12 | Modis Therapeutics Inc. | Pró-fármacos de desoxinucleosídeos para tratamento de doenças causadas por agrupamentos de nucleotídeos não balanceados |
| JP7496132B2 (ja) * | 2018-08-31 | 2024-06-06 | 国立大学法人 鹿児島大学 | 核酸アナログ及び抗b型肝炎ウイルス剤 |
| US11166976B2 (en) | 2018-11-08 | 2021-11-09 | Aligos Therapeutics, Inc. | S-antigen transport inhibiting oligonucleotide polymers and methods |
| CN113166190B (zh) * | 2018-11-23 | 2023-05-23 | 正大天晴药业集团股份有限公司 | 低聚核苷酸及前体药物 |
| AU2020315394A1 (en) | 2019-07-17 | 2022-02-17 | Nucorion Pharmaceuticals, Inc. | Cyclic deoxyribonucleotide compounds |
| CN110642910B (zh) * | 2019-09-02 | 2020-10-30 | 南开大学 | 胸苷衍生物及其制备方法和用途 |
| JP2022550454A (ja) * | 2019-10-02 | 2022-12-01 | ユニバーシティ オブ ワシントン | B型肝炎ウイルス感染の治療のための組成物及び方法 |
| CN111087421B (zh) * | 2019-12-24 | 2022-10-18 | 南京正大天晴制药有限公司 | 一种用于手性药物合成的磷酰胺化合物的制备方法 |
| US20230183282A1 (en) * | 2020-04-02 | 2023-06-15 | The Regents Of The University Of Michigan | Remdesivir and remdesivir analogs, solutions, and nanoparticle, liposomal, and microparticle compositions for treating viral infections |
| CN113493481B (zh) * | 2020-04-08 | 2025-02-18 | 北京君科华元医药科技有限公司 | 单磷酸恩替卡韦丙氨酰胺酚酯及其医药用途 |
| WO2021253376A1 (zh) * | 2020-06-19 | 2021-12-23 | 南京正大天晴制药有限公司 | 一种用于手性药物合成的磷酰胺化合物的制备方法 |
| WO2022251594A1 (en) * | 2021-05-27 | 2022-12-01 | Antios Therapeutics, Inc. | Pharmacokinetics and dose-related improvments in subjects treated with phosphoramidate clevudine prodrugs |
| WO2022256490A2 (en) * | 2021-06-03 | 2022-12-08 | Antios Therapeutics, Inc. | Improved synthesis of phosphoramidates for the treatment of hepatitis b virus |
| CN113501853B (zh) * | 2021-09-13 | 2021-12-07 | 南京颐媛生物医学研究院有限公司 | 4-硫代尿嘧啶脱氧核苷磷酸酯及其抗病毒药物用途 |
| US20250092401A1 (en) * | 2022-01-28 | 2025-03-20 | Glaxosmithkline Intellectual Property Development Limited | Combination therapy for treating hepatitis b virus infections |
| CN115260263B (zh) * | 2022-05-23 | 2025-02-21 | 浙江扬厉医药技术有限公司 | 烷基硫芳基克拉夫定磷酰胺类化合物及其应用 |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3687931A (en) | 1970-03-19 | 1972-08-29 | Syntex Corp | Halogenated purine and pyrimidine nucleosides and process therefor |
| US5587362A (en) | 1994-01-28 | 1996-12-24 | Univ. Of Ga Research Foundation | L-nucleosides |
| US7462605B2 (en) | 1998-01-23 | 2008-12-09 | Celmed Oncology (Usa), Inc. | Phosphoramidate compounds and methods of use |
| MY164523A (en) | 2000-05-23 | 2017-12-29 | Univ Degli Studi Cagliari | Methods and compositions for treating hepatitis c virus |
| US20040229839A1 (en) | 2003-05-14 | 2004-11-18 | Biocryst Pharmaceuticals, Inc. | Substituted nucleosides, preparation thereof and use as inhibitors of RNA viral polymerases |
| GB0317009D0 (en) | 2003-07-21 | 2003-08-27 | Univ Cardiff | Chemical compounds |
| EP1827460A4 (en) | 2004-12-09 | 2012-03-14 | Univ Minnesota | NUCLEOSIDE WITH ANTIVIRAL AND ANTI-CANCER EFFECT |
| ES2392544T3 (es) | 2005-06-07 | 2012-12-11 | Yale University | Métodos de tratamiento del cáncer y otras enfermedades o estados patológicos usando LFMAU y LDT |
| WO2007056596A2 (en) | 2005-11-09 | 2007-05-18 | Wayne State University | Phosphoramidate derivatives of fau |
| US7964580B2 (en) | 2007-03-30 | 2011-06-21 | Pharmasset, Inc. | Nucleoside phosphoramidate prodrugs |
| US8008264B2 (en) | 2008-04-23 | 2011-08-30 | Gilead Sciences, Inc. | 1′-substituted carba-nucleoside analogs for antiviral treatment |
| PL2552930T3 (pl) | 2010-03-31 | 2016-02-29 | Gilead Pharmasset Llc | Krystaliczny 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-diokso-3,4-dihydropirymidyn-1-(2H)-ylo)-4-fluoro-3-hydroksy-4-metylotetrahydrofuran-2-ylo)metoksy)(fenoksy)fosforylo)amino)propanian (S)-izopropylu |
| KR20130110170A (ko) | 2010-09-22 | 2013-10-08 | 앨리오스 바이오파마 인크. | 치환된 뉴클레오타이드 유사체 |
| US20120142627A1 (en) * | 2010-12-06 | 2012-06-07 | Emory University | Monophosphate prodrugs of dapd and analogs thereof |
| CN103987712B (zh) | 2011-07-19 | 2016-05-04 | 河南美泰宝生物制药有限公司 | 2’,3’-二脱氧-2’-α-氟-2’-β-C-甲基核苷和其前药 |
| MX2015005500A (es) * | 2012-10-29 | 2016-02-09 | Cocrystal Pharma Inc | Nucleotidos de pirimidina y sus profarmacos de monofosfato para el tratamiento de infecciones virales y cancer. |
| EP2920195A1 (en) | 2012-11-14 | 2015-09-23 | IDENIX Pharmaceuticals, Inc. | D-alanine ester of rp-nucleoside analog |
| EP2970357B1 (en) | 2013-03-13 | 2025-01-01 | Idenix Pharmaceuticals LLC | Amino acid phosphoramidate pronucleotides of 2'-cyano, azido and amino nucleosides for the treatment of hcv |
| CA2909273A1 (en) | 2013-04-12 | 2014-10-16 | Achillion Pharmaceuticals, Inc. | Deuterated nucleoside prodrugs useful for treating hcv |
| EP3233878B1 (en) * | 2014-12-15 | 2025-09-03 | Emory University | Phosphoramidates for the treatment of hepatitis b virus |
-
2017
- 2017-06-23 EA EA201990059A patent/EA201990059A1/ru unknown
- 2017-06-23 EP EP17816278.0A patent/EP3474863A4/en not_active Withdrawn
- 2017-06-23 KR KR1020197002039A patent/KR20190057277A/ko not_active Ceased
- 2017-06-23 AU AU2017281531A patent/AU2017281531A1/en not_active Abandoned
- 2017-06-23 SG SG11201811316YA patent/SG11201811316YA/en unknown
- 2017-06-23 CN CN201780050071.4A patent/CN109689065A/zh active Pending
- 2017-06-23 US US16/312,756 patent/US11364257B2/en active Active
- 2017-06-23 CA CA3029315A patent/CA3029315A1/en active Pending
- 2017-06-23 BR BR112018076913-4A patent/BR112018076913A2/pt not_active IP Right Cessation
- 2017-06-23 JP JP2018567034A patent/JP2019525905A/ja active Pending
- 2017-06-23 WO PCT/US2017/038963 patent/WO2017223421A1/en not_active Ceased
-
2018
- 2018-12-20 PH PH12018550207A patent/PH12018550207A1/en unknown
- 2018-12-20 IL IL263859A patent/IL263859B2/en unknown
-
2019
- 2019-01-09 ZA ZA2019/00156A patent/ZA201900156B/en unknown
-
2022
- 2022-05-06 US US17/738,435 patent/US20220280542A1/en not_active Abandoned
- 2022-05-10 JP JP2022077781A patent/JP2022116024A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP3474863A1 (en) | 2019-05-01 |
| KR20190057277A (ko) | 2019-05-28 |
| EP3474863A4 (en) | 2020-03-25 |
| AU2017281531A1 (en) | 2019-01-17 |
| EA201990059A1 (ru) | 2019-07-31 |
| CN109689065A (zh) | 2019-04-26 |
| IL263859A (en) | 2019-01-31 |
| JP2022116024A (ja) | 2022-08-09 |
| SG11201811316YA (en) | 2019-01-30 |
| JP2019525905A (ja) | 2019-09-12 |
| IL263859B2 (en) | 2023-07-01 |
| WO2017223421A1 (en) | 2017-12-28 |
| PH12018550207A1 (en) | 2019-04-15 |
| CA3029315A1 (en) | 2017-12-28 |
| BR112018076913A2 (pt) | 2019-04-02 |
| US20190350954A1 (en) | 2019-11-21 |
| US11364257B2 (en) | 2022-06-21 |
| US20220280542A1 (en) | 2022-09-08 |
| IL263859B1 (en) | 2023-03-01 |
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