MX2017016425A - Terapia con desoxinucleosidos para enfermedades generadas por grupos de nucleotidos desequilibrados, inclusive sindromes de agotamiento del adn mitocondrial. - Google Patents

Terapia con desoxinucleosidos para enfermedades generadas por grupos de nucleotidos desequilibrados, inclusive sindromes de agotamiento del adn mitocondrial.

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Publication number
MX2017016425A
MX2017016425A MX2017016425A MX2017016425A MX2017016425A MX 2017016425 A MX2017016425 A MX 2017016425A MX 2017016425 A MX2017016425 A MX 2017016425A MX 2017016425 A MX2017016425 A MX 2017016425A MX 2017016425 A MX2017016425 A MX 2017016425A
Authority
MX
Mexico
Prior art keywords
unbalanced
syndromes
groups
therapy
deoxinucleosids
Prior art date
Application number
MX2017016425A
Other languages
English (en)
Spanish (es)
Inventor
Hirano Michio
Garone Caterina
MARTI Ramon
Original Assignee
Univ Columbia
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 filed Critical Univ Columbia
Publication of MX2017016425A publication Critical patent/MX2017016425A/es

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds 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
    • A61K31/7064Compounds 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
    • A61K31/7068Compounds 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds 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
    • A61K31/7064Compounds 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
    • A61K31/7068Compounds 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
    • A61K31/7072Compounds 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds 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
    • A61K31/7064Compounds 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
    • A61K31/7076Compounds 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds 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
    • A61K31/7064Compounds 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
    • A61K31/7076Compounds 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
    • A61K31/708Compounds 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00Drugs for disorders of the muscular or neuromuscular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING 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
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813Hybridisation assays
    • C12Q1/6827Hybridisation assays for detection of mutation or polymorphism
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00Mixtures 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)
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  • Medicinal Chemistry (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
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  • 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)
MX2017016425A 2015-06-17 2016-06-17 Terapia con desoxinucleosidos para enfermedades generadas por grupos de nucleotidos desequilibrados, inclusive sindromes de agotamiento del adn mitocondrial. MX2017016425A (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 (1)

Publication Number Publication Date
MX2017016425A true MX2017016425A (es) 2018-12-11

Family

ID=57546446

Family Applications (2)

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.
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.

Family Applications After (1)

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.

Country Status (24)

Country Link
US (5) US10471087B2 (https=)
EP (3) EP3310362B1 (https=)
JP (3) JP6599484B2 (https=)
KR (3) KR20180039624A (https=)
CN (2) CN116726035A (https=)
AU (3) AU2016280293B2 (https=)
BR (2) BR112017027079B1 (https=)
CA (1) CA2989653A1 (https=)
CY (2) CY1122605T1 (https=)
DK (2) DK3505174T3 (https=)
ES (2) ES2748556T3 (https=)
HK (1) HK1252133A1 (https=)
HR (2) HRP20191794T1 (https=)
HU (2) HUE046399T2 (https=)
IL (3) IL275256B2 (https=)
LT (2) LT3310362T (https=)
MX (2) MX2017016425A (https=)
PL (2) PL3505174T3 (https=)
PT (2) PT3505174T (https=)
RS (2) RS59724B1 (https=)
RU (1) RU2721492C2 (https=)
SI (2) SI3505174T1 (https=)
SM (2) SMT202000399T1 (https=)
WO (1) WO2016205671A1 (https=)

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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
JP6599484B2 (ja) * 2015-06-17 2019-10-30 ザ・トラスティーズ・オブ・コロンビア・ユニバーシティ・イン・ザ・シティ・オブ・ニューヨーク ミトコンドリアdna枯渇症候群を含む不均衡なヌクレオチドプールによって引き起こされる疾患のためのデオキシヌクレオシド療法
WO2017112701A1 (en) 2015-12-22 2017-06-29 Zogenix International Limited Metabolism resistant fenfluramine analogs and methods of using the same
PT4293009T (pt) 2015-12-22 2025-09-08 Zogenix International Ltd Composições de fenfluramina e métodos de preparação das mesmas
AU2017315273B2 (en) 2016-08-24 2021-04-29 Zogenix International Limited Formulation for inhibiting formation of 5-HT 2B agonists and methods of using same
US11649442B2 (en) 2017-09-08 2023-05-16 The Regents Of The University Of California RNA-guided endonuclease fusion polypeptides and methods of use thereof
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
KR20210009317A (ko) 2018-04-18 2021-01-26 더 트러스티스 오브 콜롬비아 유니버시티 인 더 시티 오브 뉴욕 미토콘드리아 dna 고갈 증후군을 포함하는 불균형 뉴클레오타이드 풀에 의해 초래된 질환에 대한 유전자 요법
EP3790537A1 (en) 2018-05-11 2021-03-17 Zogenix International Limited Compositions and methods for treating seizure-induced sudden death
AU2019384963B2 (en) 2018-11-19 2022-05-26 Zogenix International Limited Methods of treating Rett syndrome using fenfluramine
CA3150755A1 (en) * 2019-08-19 2021-02-25 Modis Therapeutics, Inc. Polymorphic forms of deoxycytidine, compositions comprising the same and uses
US20230000894A1 (en) * 2019-09-05 2023-01-05 Mitorainbow Therapeutics, Inc. Treating mitochondrial dna depletion disorders
AU2021236683A1 (en) 2020-03-19 2022-11-17 Intellia Therapeutics, Inc. Methods and compositions for directed genome editing
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
EP4268829A4 (en) * 2020-12-28 2024-11-27 Yamasa Corporation MUSCLE ATROPHY INHIBITOR AND METHOD FOR INHIBITING MUSCLE ATROPHY
EP4313068A4 (en) 2021-03-26 2024-12-25 UCB Biosciences, Inc. Aqueous solutions containing purines and pyrimidines and uses thereof
US20230000890A1 (en) * 2021-06-18 2023-01-05 Zogenix Mds, Inc. Prodrugs of Deoxynucleosides for Treatment of Mitochondrial Diseases Caused by Unbalanced Nucleotide Pools
WO2024015453A1 (en) * 2022-07-12 2024-01-18 Zogenix Mds, Inc. Methods for increasing the bioavailability of nucleoside medicinal agents
EP4687918A2 (en) * 2023-03-30 2026-02-11 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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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
BR112017025839A2 (en) * 2015-06-05 2018-08-14 Fundació Hospital Universitari Vall D'hebron - Institut De Recerca treatment of mitochondrial diseases
JP6599484B2 (ja) * 2015-06-17 2019-10-30 ザ・トラスティーズ・オブ・コロンビア・ユニバーシティ・イン・ザ・シティ・オブ・ニューヨーク ミトコンドリアdna枯渇症候群を含む不均衡なヌクレオチドプールによって引き起こされる疾患のためのデオキシヌクレオシド療法

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CA2989653A1 (en) 2016-12-22
CY1122605T1 (el) 2021-03-12
AU2021250841B2 (en) 2023-02-09
EP3310362A1 (en) 2018-04-25
JP2020019792A (ja) 2020-02-06
EP3310362A4 (en) 2018-12-19
DK3505174T3 (da) 2020-07-13
IL275256A (en) 2020-07-30
RS60572B1 (sr) 2020-08-31
SMT202000399T1 (it) 2020-09-10
RU2020112901A (ru) 2020-06-05
SI3505174T1 (sl) 2021-02-26
HK1252133A1 (zh) 2019-05-17
US20250360154A1 (en) 2025-11-27
AU2016280293B2 (en) 2020-07-02
PL3310362T3 (pl) 2020-04-30
CN116726035A (zh) 2023-09-12
EP3505174B1 (en) 2020-04-29
SMT201900571T1 (it) 2019-11-13
EP3505174A1 (en) 2019-07-03
KR20220018623A (ko) 2022-02-15
IL256331B (en) 2020-08-31
HUE046399T2 (hu) 2020-03-30
EP3569236A1 (en) 2019-11-20
AU2020204042B2 (en) 2021-07-15
US11110111B2 (en) 2021-09-07
US20180133241A1 (en) 2018-05-17
JP2018521993A (ja) 2018-08-09
WO2016205671A1 (en) 2016-12-22
AU2020204042A1 (en) 2020-07-09
SI3310362T1 (sl) 2020-02-28
DK3310362T3 (da) 2019-10-07
US12251392B2 (en) 2025-03-18
ES2748556T3 (es) 2020-03-17
EP3310362B1 (en) 2019-08-28
JP6599484B2 (ja) 2019-10-30
IL275255A (en) 2020-07-30
ES2808148T3 (es) 2021-02-25
MX2020000269A (es) 2022-01-03
PT3310362T (pt) 2019-10-29
RU2018101305A3 (https=) 2019-10-31
AU2016280293A1 (en) 2018-02-08
IL275256B2 (en) 2023-09-01
RS59724B1 (sr) 2020-01-31
RU2721492C2 (ru) 2020-05-19
CY1123107T1 (el) 2021-10-29
IL275256B1 (en) 2023-05-01
JP2020019791A (ja) 2020-02-06
WO2016205671A9 (en) 2018-01-04
KR20250048602A (ko) 2025-04-09
LT3505174T (lt) 2020-09-10
CN107847512A (zh) 2018-03-27
JP7036782B2 (ja) 2022-03-15
KR20180039624A (ko) 2018-04-18
HRP20191794T1 (hr) 2020-02-07
RU2018101305A (ru) 2019-07-17
IL256331A (en) 2018-02-28
HRP20200949T1 (hr) 2020-10-02
AU2021250841A1 (en) 2021-11-04
JP6675037B2 (ja) 2020-04-01
US20230277577A1 (en) 2023-09-07
US20200038424A1 (en) 2020-02-06
BR112017027079B1 (pt) 2021-04-27
HUE050678T2 (hu) 2020-12-28
US11666592B2 (en) 2023-06-06
MX389016B (es) 2025-03-20
BR122020021913B1 (pt) 2021-07-06
LT3310362T (lt) 2019-11-11
IL275255B (en) 2021-04-29
PL3505174T3 (pl) 2020-08-24
PT3505174T (pt) 2020-07-06
US20210244754A1 (en) 2021-08-12
US10471087B2 (en) 2019-11-12

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