MX389016B - Terapia con desoxinucleósidos para enfermedades generadas por grupos de nucleótidos desequilibrados, inclusive síndromes de agotamiento del adn mitocondrial. - Google Patents

Terapia con desoxinucleósidos para enfermedades generadas por grupos de nucleótidos desequilibrados, inclusive síndromes de agotamiento del adn mitocondrial.

Info

Publication number
MX389016B
MX389016B MX2020000269A MX2020000269A MX389016B MX 389016 B MX389016 B MX 389016B MX 2020000269 A MX2020000269 A MX 2020000269A MX 2020000269 A MX2020000269 A MX 2020000269A MX 389016 B MX389016 B MX 389016B
Authority
MX
Mexico
Prior art keywords
mitochondrial dna
dna depletion
diseases caused
administration
nucleotide groups
Prior art date
Application number
MX2020000269A
Other languages
English (en)
Spanish (es)
Other versions
MX2020000269A (es
Inventor
Caterina Garone
Michio Hirano
Ramon Marti
Original Assignee
Univ Columbia
Fundacio Hospital Univ Vall D´Hebron Institut De Recerca
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Univ Columbia, Fundacio Hospital Univ Vall D´Hebron Institut De Recerca filed Critical Univ Columbia
Publication of MX2020000269A publication Critical patent/MX2020000269A/es
Publication of MX389016B publication Critical patent/MX389016B/es

Links

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
    • 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
    • A61K31/33—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
    • A61K31/70—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
    • 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
    • A61K31/7076—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 containing purines, e.g. adenosine, adenylic 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
    • A61K31/7076—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 containing purines, e.g. adenosine, adenylic acid
    • A61K31/708—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 containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
    • 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
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • 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
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6827—Hybridisation assays for detection of mutation or polymorphism
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • 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

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  • 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)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Hematology (AREA)
  • Biotechnology (AREA)
  • Immunology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Analytical Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Microbiology (AREA)
  • Urology & Nephrology (AREA)
  • Physics & Mathematics (AREA)
  • Biochemistry (AREA)
  • Obesity (AREA)
  • Child & Adolescent Psychology (AREA)
  • Diabetes (AREA)
  • Biophysics (AREA)
  • General Physics & Mathematics (AREA)
MX2020000269A 2015-06-17 2016-06-17 Terapia con desoxinucleósidos para enfermedades generadas por grupos de nucleótidos desequilibrados, inclusive síndromes de agotamiento del adn mitocondrial. MX389016B (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201562180914P 2015-06-17 2015-06-17
PCT/US2016/038110 WO2016205671A1 (en) 2015-06-17 2016-06-17 Deoxynucleoside therapy for diseases caused by unbalanced nucleotide pools including mitochondrial dna depletion syndromes

Publications (2)

Publication Number Publication Date
MX2020000269A MX2020000269A (es) 2022-01-03
MX389016B true MX389016B (es) 2025-03-20

Family

ID=57546446

Family Applications (2)

Application Number Title Priority Date Filing Date
MX2020000269A MX389016B (es) 2015-06-17 2016-06-17 Terapia con desoxinucleósidos para enfermedades generadas por grupos de nucleótidos desequilibrados, inclusive síndromes de agotamiento del adn mitocondrial.
MX2017016425A MX2017016425A (es) 2015-06-17 2016-06-17 Terapia con desoxinucleosidos para enfermedades generadas por grupos de nucleotidos desequilibrados, inclusive sindromes de agotamiento del adn mitocondrial.

Family Applications After (1)

Application Number Title Priority Date Filing Date
MX2017016425A MX2017016425A (es) 2015-06-17 2016-06-17 Terapia con desoxinucleosidos para enfermedades generadas por grupos de nucleotidos desequilibrados, inclusive sindromes de agotamiento del adn mitocondrial.

Country Status (24)

Country Link
US (5) US10471087B2 (enExample)
EP (3) EP3505174B1 (enExample)
JP (3) JP6599484B2 (enExample)
KR (3) KR20220018623A (enExample)
CN (2) CN116726035A (enExample)
AU (3) AU2016280293B2 (enExample)
BR (2) BR112017027079B1 (enExample)
CA (1) CA2989653A1 (enExample)
CY (2) CY1122605T1 (enExample)
DK (2) DK3505174T3 (enExample)
ES (2) ES2808148T3 (enExample)
HK (1) HK1252133A1 (enExample)
HR (2) HRP20191794T1 (enExample)
HU (2) HUE050678T2 (enExample)
IL (3) IL275256B2 (enExample)
LT (2) LT3505174T (enExample)
MX (2) MX389016B (enExample)
PL (2) PL3310362T3 (enExample)
PT (2) PT3505174T (enExample)
RS (2) RS60572B1 (enExample)
RU (1) RU2721492C2 (enExample)
SI (2) SI3505174T1 (enExample)
SM (2) SMT202000399T1 (enExample)
WO (1) WO2016205671A1 (enExample)

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US9549909B2 (en) 2013-05-03 2017-01-24 The Katholieke Universiteit Leuven Method for the treatment of dravet syndrome
US10292996B2 (en) 2015-03-26 2019-05-21 The Trustees Of Columbia University In The City Of New York Deoxyribonucleoside monophospate bypass therapy for mitochondrial DNA depletion syndrome
LT3505174T (lt) * 2015-06-17 2020-09-10 The Trustees Of Columbia University In The City Of New York Deoksinukleozidų terapija, skirta gydyti ligas, kurias sukelia nesubalansuoti nukleotidų kiekiai, įskaitant mitochondrinės dnr išsekimo sindromus
US20170174614A1 (en) 2015-12-22 2017-06-22 Zogenix International Limited Metabolism resistant fenfluramine analogs and methods of using the same
CN108883399B (zh) 2015-12-22 2021-06-22 周格尼克斯国际有限公司 芬氟拉明组合物及其制备方法
RU2021106383A (ru) 2016-08-24 2021-04-05 Зодженикс Интернэшнл Лимитед Состав для ингибирования образования агонистов 5-ht2b и способы его применения
WO2019051097A1 (en) 2017-09-08 2019-03-14 The Regents Of The University Of California RNA-GUIDED ENDONUCLEASE FUSION POLYPEPTIDES AND METHODS OF USING SAME
US10682317B2 (en) 2017-09-26 2020-06-16 Zogenix International Limited Ketogenic diet compatible fenfluramine formulation
US11628182B2 (en) * 2018-04-12 2023-04-18 Zogenix Mds, Inc. Prodrugs of deoxynucleosides for treatment of diseases cased by unbalanced nucleotide pools
BR112020021324A2 (pt) 2018-04-18 2021-01-19 The Trustees Of Columbia University In The City Of New York Terapia gênica para doenças causadas por pools de nucleotídeos em desequilíbrio incluindo síndromes de depleção do dna mitocondrial
WO2019216919A1 (en) 2018-05-11 2019-11-14 Zogenix International Limited Compositions and methods for treating seizure-induced sudden death
US12144787B2 (en) 2018-11-19 2024-11-19 Zogenix International Limited Method of treating patients with a mutation in cyclin-dependent kinase-like 5 (CDKL5)
JP7769603B2 (ja) * 2019-08-19 2025-11-13 ユーシービー バイオサイエンシズ，インコーポレイテッド デオキシシチジンの多形形態、それを含む組成物および使用
JP2022546611A (ja) * 2019-09-05 2022-11-04 ミトレインボー セラピューティクス，インコーポレーテッド ミトコンドリアｄｎａ枯渇障害の処置
CN115667505A (zh) 2020-03-19 2023-01-31 因特利亚治疗公司 用于定向基因组编辑的方法和组合物
US11612574B2 (en) 2020-07-17 2023-03-28 Zogenix International Limited Method of treating patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
US20220096514A1 (en) * 2020-09-29 2022-03-31 Zogenix International Limited Methods of treating thymidine kinase 2 deficiency by administering deoxycytidine and deoxythymidine
WO2022145439A1 (ja) * 2020-12-28 2022-07-07 ヤマサ醤油株式会社 筋萎縮抑制剤及び筋萎縮を抑制させる方法
JP2024515025A (ja) 2021-03-26 2024-04-04 ゾジェニックス，インコーポレイテッド プリン及びピリミジンを含有する水性溶液及びその使用
AU2022291783A1 (en) * 2021-06-18 2024-02-01 Ucb Biosciences, Inc. Prodrugs of deoxynucleosides for treatment of mitochondrial diseases caused by unbalanced nucleotide pools
JP2025522100A (ja) * 2022-07-12 2025-07-10 ユーシービー バイオサイエンシス、インコーポレイテッド ヌクレオシド薬剤のバイオアベイラビリティを増加させる方法
WO2024206595A2 (en) * 2023-03-30 2024-10-03 The Trustees Of Columbia University In The City Of New York Pharmacological therapy for mitochondrial dna depletion deletions syndrome involving mutations in the guk1 gene

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CN101120947B (zh) * 1998-08-10 2010-11-24 艾丹尼克斯(开曼)有限公司 用于治疗乙型肝炎的β-L-2′-脱氧-核苷
ES2298130T3 (es) * 1999-02-23 2008-05-16 The Regents Of The University Of California Uso de triacetiluridina para el tratamiento de trastornos mitocondriales.
ATE275406T1 (de) * 2000-05-26 2004-09-15 Idenix Cayman Ltd Methoden zur behandlung von delta hepatitis virus infektionen mit beta-l-2' deoxy-nucleosiden
WO2012125848A2 (en) 2011-03-16 2012-09-20 Baylor College Of Medicine A method for comprehensive sequence analysis using deep sequencing technology
US10292996B2 (en) 2015-03-26 2019-05-21 The Trustees Of Columbia University In The City Of New York Deoxyribonucleoside monophospate bypass therapy for mitochondrial DNA depletion syndrome
IL289747B2 (en) * 2015-06-05 2025-10-01 Fundacio Hospital Univ Vall Dhebron Institut De Recerca Combination of deoxyribonucleosides for the treatment of mitochondrial DNA depletion syndrome and/or deletion syndrome
LT3505174T (lt) * 2015-06-17 2020-09-10 The Trustees Of Columbia University In The City Of New York Deoksinukleozidų terapija, skirta gydyti ligas, kurias sukelia nesubalansuoti nukleotidų kiekiai, įskaitant mitochondrinės dnr išsekimo sindromus

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JP2020019792A (ja) 2020-02-06
CY1122605T1 (el) 2021-03-12
AU2020204042A1 (en) 2020-07-09
PL3310362T3 (pl) 2020-04-30
DK3505174T3 (da) 2020-07-13
SMT201900571T1 (it) 2019-11-13
EP3310362B1 (en) 2019-08-28
AU2020204042B2 (en) 2021-07-15
RU2721492C2 (ru) 2020-05-19
JP6675037B2 (ja) 2020-04-01
RS59724B1 (sr) 2020-01-31
US12251392B2 (en) 2025-03-18
RU2018101305A (ru) 2019-07-17
EP3310362A1 (en) 2018-04-25
IL275256B2 (en) 2023-09-01
HRP20200949T1 (hr) 2020-10-02
US20250360154A1 (en) 2025-11-27
EP3505174B1 (en) 2020-04-29
IL275256B1 (en) 2023-05-01
EP3310362A4 (en) 2018-12-19
WO2016205671A1 (en) 2016-12-22
PL3505174T3 (pl) 2020-08-24
EP3505174A1 (en) 2019-07-03
HK1252133A1 (zh) 2019-05-17
PT3505174T (pt) 2020-07-06
US20210244754A1 (en) 2021-08-12
SI3505174T1 (sl) 2021-02-26
US20200038424A1 (en) 2020-02-06
JP7036782B2 (ja) 2022-03-15
US20230277577A1 (en) 2023-09-07
PT3310362T (pt) 2019-10-29
ES2748556T3 (es) 2020-03-17
CY1123107T1 (el) 2021-10-29
JP2020019791A (ja) 2020-02-06
JP2018521993A (ja) 2018-08-09
ES2808148T3 (es) 2021-02-25
IL275256A (en) 2020-07-30
RU2020112901A (ru) 2020-06-05
HUE046399T2 (hu) 2020-03-30
EP3569236A1 (en) 2019-11-20
KR20250048602A (ko) 2025-04-09
IL275255A (en) 2020-07-30
HUE050678T2 (hu) 2020-12-28
IL256331A (en) 2018-02-28
CN116726035A (zh) 2023-09-12
AU2016280293B2 (en) 2020-07-02
BR122020021913B1 (pt) 2021-07-06
SMT202000399T1 (it) 2020-09-10
AU2021250841B2 (en) 2023-02-09
RU2018101305A3 (enExample) 2019-10-31
BR112017027079B1 (pt) 2021-04-27
DK3310362T3 (da) 2019-10-07
IL256331B (en) 2020-08-31
WO2016205671A9 (en) 2018-01-04
HRP20191794T1 (hr) 2020-02-07
US11110111B2 (en) 2021-09-07
RS60572B1 (sr) 2020-08-31
IL275255B (en) 2021-04-29
AU2016280293A1 (en) 2018-02-08
LT3505174T (lt) 2020-09-10
LT3310362T (lt) 2019-11-11
KR20220018623A (ko) 2022-02-15
US20180133241A1 (en) 2018-05-17
US10471087B2 (en) 2019-11-12
MX2020000269A (es) 2022-01-03
SI3310362T1 (sl) 2020-02-28
AU2021250841A1 (en) 2021-11-04
MX2017016425A (es) 2018-12-11
JP6599484B2 (ja) 2019-10-30
CA2989653A1 (en) 2016-12-22
US11666592B2 (en) 2023-06-06
KR20180039624A (ko) 2018-04-18
CN107847512A (zh) 2018-03-27

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