MX2016007176A - Composiciones y metodos para obtener (r)-reticulina y precursores de las misma. - Google Patents

Composiciones y metodos para obtener (r)-reticulina y precursores de las misma.

Info

Publication number
MX2016007176A
MX2016007176A MX2016007176A MX2016007176A MX2016007176A MX 2016007176 A MX2016007176 A MX 2016007176A MX 2016007176 A MX2016007176 A MX 2016007176A MX 2016007176 A MX2016007176 A MX 2016007176A MX 2016007176 A MX2016007176 A MX 2016007176A
Authority
MX
Mexico
Prior art keywords
reticuline
precursors
methods
compositions
making
Prior art date
Application number
MX2016007176A
Other languages
English (en)
Other versions
MX364825B (es
Inventor
James Facchini Peter
Cameron Farrow Scott
Arthur Welch Beaudoin Guillaume
Original Assignee
Epimeron Inc
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 Epimeron Inc filed Critical Epimeron Inc
Publication of MX2016007176A publication Critical patent/MX2016007176A/es
Publication of MX364825B publication Critical patent/MX364825B/es

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01H—NEW PLANTS OR NON-TRANSGENIC PROCESSES FOR OBTAINING THEM; PLANT REPRODUCTION BY TISSUE CULTURE TECHNIQUES
    • A01H1/00—Processes for modifying genotypes ; Plants characterised by associated natural traits
    • A01H1/04—Processes of selection involving genotypic or phenotypic markers; Methods of using phenotypic markers for selection
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/52—Genes encoding for enzymes or proenzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/10—Nitrogen as only ring hetero atom
    • C12P17/12—Nitrogen as only ring hetero atom containing a six-membered hetero ring
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01H—NEW PLANTS OR NON-TRANSGENIC PROCESSES FOR OBTAINING THEM; PLANT REPRODUCTION BY TISSUE CULTURE TECHNIQUES
    • A01H1/00—Processes for modifying genotypes ; Plants characterised by associated natural traits
    • A01H1/06—Processes for producing mutations, e.g. treatment with chemicals or with radiation
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01H—NEW PLANTS OR NON-TRANSGENIC PROCESSES FOR OBTAINING THEM; PLANT REPRODUCTION BY TISSUE CULTURE TECHNIQUES
    • A01H5/00—Angiosperms, i.e. flowering plants, characterised by their plant parts; Angiosperms characterised otherwise than by their botanic taxonomy
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
    • C07D217/24—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
    • C12N15/8216—Methods for controlling, regulating or enhancing expression of transgenes in plant cells
    • C12N15/8218—Antisense, co-suppression, viral induced gene silencing [VIGS], post-transcriptional induced gene silencing [PTGS]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09—Recombinant DNA-technology
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
    • C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
    • C12N15/8242—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits
    • C12N15/8243—Phenotypically and genetically modified plants via recombinant DNA technology with non-agronomic quality (output) traits, e.g. for industrial processing; Value added, non-agronomic traits involving biosynthetic or metabolic pathways, i.e. metabolic engineering, e.g. nicotine, caffeine
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/0004—Oxidoreductases (1.)
    • C12N9/0006—Oxidoreductases (1.) acting on CH-OH groups as donors (1.1)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/0004—Oxidoreductases (1.)
    • C12N9/0071—Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14)
    • C12N9/0077—Oxidoreductases (1.) acting on paired donors with incorporation of molecular oxygen (1.14) with a reduced iron-sulfur protein as one donor (1.14.15)
    • C12N9/0081—Cholesterol monooxygenase (cytochrome P 450scc)(1.14.15.6)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/1085—Transferases (2.) transferring alkyl or aryl groups other than methyl groups (2.5)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/10—Nitrogen as only ring hetero atom
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y101/00—Oxidoreductases acting on the CH-OH group of donors (1.1)
    • C12Y101/01—Oxidoreductases acting on the CH-OH group of donors (1.1) with NAD+ or NADP+ as acceptor (1.1.1)
    • C12Y101/01247—Codeinone reductase (NADPH) (1.1.1.247)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y205/00—Transferases transferring alkyl or aryl groups, other than methyl groups (2.5)
    • C12Y205/01—Transferases transferring alkyl or aryl groups, other than methyl groups (2.5) transferring alkyl or aryl groups, other than methyl groups (2.5.1)
    • C12Y205/01059—Protein geranylgeranyltransferase type I (2.5.1.59)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Cell Biology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Botany (AREA)
  • Developmental Biology & Embryology (AREA)
  • Environmental Sciences (AREA)
  • Virology (AREA)
  • Nutrition Science (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Analytical Chemistry (AREA)
  • Physiology (AREA)
  • Immunology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Other In-Based Heterocyclic Compounds (AREA)
  • Breeding Of Plants And Reproduction By Means Of Culturing (AREA)

Abstract

Métodos que se pueden usar para la fabricación del compuesto químico (R)-reticulina y precursores sintéticos de la misma. También se proporcionan composiciones útiles para la síntesis de (R)-reticulina y precursores sintéticos.
MX2016007176A 2013-12-04 2014-12-03 Composiciones y metodos para obtener (r)-reticulina y precursores de las misma. MX364825B (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361911759P 2013-12-04 2013-12-04
US201462050399P 2014-09-15 2014-09-15
PCT/CA2014/051164 WO2015081437A1 (en) 2013-12-04 2014-12-03 Compositions and methods for making (r)-reticuline and precursors thereof

Publications (2)

Publication Number Publication Date
MX2016007176A true MX2016007176A (es) 2016-12-08
MX364825B MX364825B (es) 2019-05-08

Family

ID=53272687

Family Applications (1)

Application Number Title Priority Date Filing Date
MX2016007176A MX364825B (es) 2013-12-04 2014-12-03 Composiciones y metodos para obtener (r)-reticulina y precursores de las misma.

Country Status (14)

Country Link
US (3) US10190141B2 (es)
EP (2) EP4289959A1 (es)
JP (1) JP6783655B2 (es)
KR (2) KR102018240B1 (es)
CN (3) CN115927139A (es)
AU (4) AU2014360597B2 (es)
BR (1) BR112016012595B1 (es)
CA (1) CA2932448C (es)
DK (1) DK3077513T3 (es)
ES (1) ES2961516T3 (es)
IL (2) IL245970B (es)
MX (1) MX364825B (es)
RU (1) RU2729065C2 (es)
WO (1) WO2015081437A1 (es)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3865580A1 (en) 2013-03-15 2021-08-18 The Board of Trustees of the Leland Stanford Junior University Benzylisoquinoline alkaloids (bia) producing microbes, and methods of making and using the same
EP3770267A1 (en) 2013-11-04 2021-01-27 The Board of Trustees of the Leland Stanford Junior University Benzylisoquinoline alkaloid (bia) precursor producing microbes, and methods of making and using the same
RU2729065C2 (ru) * 2013-12-04 2020-08-04 Эпимерон Инк. Композиции и способы получения (R)-ретикулина и его предшественников
CA2946812C (en) 2014-05-16 2023-10-10 The Unversity Of York Cytochrome p450 fusion protein
US10752903B2 (en) 2015-05-04 2020-08-25 The Board Of Trustees Of The Leland Stanford Junior University Benzylisoquinoline alkaloid (BIA) precursor producing microbes, and methods of making and using the same
KR20180016396A (ko) * 2015-05-08 2018-02-14 더 보드 어브 트러스티스 어브 더 리랜드 스탠포드 주니어 유니버시티 에피머라제 및 벤질아이소퀴놀린 알칼로이드를 제조하는 방법
GB201511156D0 (en) * 2015-06-24 2015-08-05 Glaxosmithkline Australia Pty Ltd And University Of York Production of alkaloids
US11142780B2 (en) 2016-06-27 2021-10-12 Antheia, Inc. Compositions and methods for making benzylisoquinoline alkaloids, morphinan alkaloids, thebaine, and derivatives thereof
AU2017289304B2 (en) * 2016-06-27 2023-09-28 Antheia, Inc. Polynucleotides and polypeptides useful for making alkaloid compounds
CN106119265B (zh) * 2016-06-30 2019-04-30 湖南美可达生物资源股份有限公司 博落回中参与血根碱与白屈菜红碱合成的细胞色素p450酶基因及其应用
KR20190084262A (ko) 2016-10-18 2019-07-16 앤테이아 인코포레이티드 노르-오피오이드 및 날-오피오이드 벤질이소퀴놀린 알칼로이드를 생산하는 방법
BR112020002050A2 (pt) 2017-08-03 2020-09-08 Antheia, Inc. epimerases engenheiradas alcaloides benzilisoquinolina e métodos de produção de alcaloides benzilisoquinolina
CA3090410A1 (en) 2018-02-08 2019-08-15 Antheia, Inc. Methods of producing morphinan alkaloids and derivatives
JPWO2020262107A1 (es) 2019-06-24 2020-12-30
WO2024100063A1 (en) 2022-11-08 2024-05-16 River Stone Biotech Aps Genetically modified benzylisoquinoline alkaloid-producing host cells with modified efflux transporter gene expression

Family Cites Families (12)

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Publication number Priority date Publication date Assignee Title
US3785927A (en) 1973-02-12 1974-01-15 Merck & Co Inc Process for converting(-)reticuline to(+)salutaridine
GB1408729A (en) * 1973-08-13 1975-10-01 Lilly Co Eli Sulphilimine compounds
US5268463A (en) 1986-11-11 1993-12-07 Jefferson Richard A Plant promoter α-glucuronidase gene construct
AUPP946399A0 (en) 1999-03-26 1999-04-22 Johnson & Johnson Research Pty. Limited Codeinone reductase from alkaloid poppy
JPWO2005033305A1 (ja) * 2003-09-17 2007-11-29 国立大学法人京都大学 ＲＮＡｉ法を用いた有用アルカロイド生合成中間体の生産法
EP1837396A1 (en) * 2006-03-23 2007-09-26 Institut für Pflanzenbiochemie-IPB Salutaridine reductase and morphine biosynthesis
US8975063B2 (en) 2006-10-19 2015-03-10 California Institute Of Technology Compositions and methods for producing benzylisoquinoline alkaloids
WO2011058446A2 (en) 2009-11-12 2011-05-19 Uti Limited Partnership Thebaine 6-o-demethylase and codeine o-demethylase from papaver somniferum
RU2729065C2 (ru) * 2013-12-04 2020-08-04 Эпимерон Инк. Композиции и способы получения (R)-ретикулина и его предшественников
WO2015103711A1 (en) 2014-01-13 2015-07-16 Valorbec Société en Commandite Method of making a benzylisoquinoline alkaloid (bia) metabolite, enzymes therefore
CA2946812C (en) * 2014-05-16 2023-10-10 The Unversity Of York Cytochrome p450 fusion protein
KR20180016396A (ko) 2015-05-08 2018-02-14 더 보드 어브 트러스티스 어브 더 리랜드 스탠포드 주니어 유니버시티 에피머라제 및 벤질아이소퀴놀린 알칼로이드를 제조하는 방법

Also Published As

Publication number Publication date
CN105980563A (zh) 2016-09-28
CA2932448A1 (en) 2015-06-11
AU2014360597A1 (en) 2016-06-09
DK3077513T3 (da) 2023-10-23
BR112016012595B1 (pt) 2024-02-27
KR20160093042A (ko) 2016-08-05
AU2020200131A1 (en) 2020-01-30
AU2020201743B2 (en) 2022-03-17
US20190241919A1 (en) 2019-08-08
WO2015081437A1 (en) 2015-06-11
CA2932448C (en) 2021-08-31
JP6783655B2 (ja) 2020-11-11
US11613770B2 (en) 2023-03-28
CN115927139A (zh) 2023-04-07
AU2014360597B2 (en) 2020-01-30
IL271289B (en) 2022-04-01
EP3077513A4 (en) 2017-06-21
AU2022279419A1 (en) 2023-01-19
EP3077513B1 (en) 2023-08-23
MX364825B (es) 2019-05-08
IL271289A (en) 2020-01-30
RU2729065C2 (ru) 2020-08-04
ES2961516T3 (es) 2024-03-12
KR102491060B1 (ko) 2023-01-20
IL245970A0 (en) 2016-07-31
CN105980563B (zh) 2022-08-30
KR102018240B1 (ko) 2019-09-04
EP4289959A1 (en) 2023-12-13
BR112016012595A2 (pt) 2017-09-26
US10190141B2 (en) 2019-01-29
US20160312256A1 (en) 2016-10-27
CN115927140A (zh) 2023-04-07
AU2020201743A1 (en) 2020-03-26
US20240002894A1 (en) 2024-01-04
EP3077513A1 (en) 2016-10-12
JP2017500024A (ja) 2017-01-05
KR20190108160A (ko) 2019-09-23
IL245970B (en) 2019-12-31

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