PL3510049T3 - Warianty kwaśnej alfa glukozydazy i ich zastosowania - Google Patents

Warianty kwaśnej alfa glukozydazy i ich zastosowania

Info

Publication number
PL3510049T3
PL3510049T3 PL17768082.4T PL17768082T PL3510049T3 PL 3510049 T3 PL3510049 T3 PL 3510049T3 PL 17768082 T PL17768082 T PL 17768082T PL 3510049 T3 PL3510049 T3 PL 3510049T3
Authority
PL
Poland
Prior art keywords
acid
alpha glucosidase
glucosidase variants
variants
alpha
Prior art date
Application number
PL17768082.4T
Other languages
English (en)
Inventor
Federico Mingozzi
Giuseppe RONZITTI
Pasqualina COLELLA
Francesco PUZZO
Original Assignee
Inserm - Institut National De La Santé Et De La Recherche Médicale
Centre National De La Recherche Scientifique
Association Institut De Myologie
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 Inserm - Institut National De La Santé Et De La Recherche Médicale, Centre National De La Recherche Scientifique, Association Institut De Myologie filed Critical Inserm - Institut National De La Santé Et De La Recherche Médicale
Publication of PL3510049T3 publication Critical patent/PL3510049T3/pl

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/34—Muscles; Smooth muscle cells; Heart; Cardiac stem cells; Myoblasts; Myocytes; Cardiomyocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • A61K35/37—Digestive system
    • A61K35/407—Liver; Hepatocytes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
    • A61K38/46—Hydrolases (3)
    • A61K38/47—Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
    • 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
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • 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
    • 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
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86—Viral vectors
    • 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
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/0652—Cells of skeletal and connective tissues; Mesenchyme
    • C12N5/0658—Skeletal muscle cells, e.g. myocytes, myotubes, myoblasts
    • 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
    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
    • C12N5/067—Hepatocytes
    • 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
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • 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
    • C12N9/14—Hydrolases (3)
    • C12N9/24—Hydrolases (3) acting on glycosyl compounds (3.2)
    • C12N9/2402—Hydrolases (3) acting on glycosyl compounds (3.2) hydrolysing O- and S- glycosyl compounds (3.2.1)
    • C12N9/2405—Glucanases
    • C12N9/2408—Glucanases acting on alpha -1,4-glucosidic bonds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/02—Fusion polypeptide containing a localisation/targetting motif containing a signal sequence
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/06—Fusion polypeptide containing a localisation/targetting motif containing a lysosomal/endosomal localisation signal
    • 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
    • C12N2510/00—Genetically modified cells
    • 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
    • C12N2740/00—Reverse transcribing RNA viruses
    • C12N2740/00011—Details
    • C12N2740/10011—Retroviridae
    • C12N2740/15011—Lentivirus, not HIV, e.g. FIV, SIV
    • C12N2740/15041—Use of virus, viral particle or viral elements as a vector
    • C12N2740/15043—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • 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
    • C12N2750/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssDNA viruses
    • C12N2750/00011—Details
    • C12N2750/14011—Parvoviridae
    • C12N2750/14111—Dependovirus, e.g. adenoassociated viruses
    • C12N2750/14141—Use of virus, viral particle or viral elements as a vector
    • C12N2750/14143—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
    • 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
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/50—Vector systems having a special element relevant for transcription regulating RNA stability, not being an intron, e.g. poly A signal
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y302/00—Hydrolases acting on glycosyl compounds, i.e. glycosylases (3.2)
    • C12Y302/01—Glycosidases, i.e. enzymes hydrolysing O- and S-glycosyl compounds (3.2.1)
    • C12Y302/0102—Alpha-glucosidase (3.2.1.20)

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Virology (AREA)
  • Cell Biology (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Developmental Biology & Embryology (AREA)
  • Immunology (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Physiology (AREA)
  • Vascular Medicine (AREA)
  • Nutrition Science (AREA)
  • Cardiology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
PL17768082.4T 2016-09-12 2017-09-12 Warianty kwaśnej alfa glukozydazy i ich zastosowania PL3510049T3 (pl)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP16306149.2A EP3293203A1 (en) 2016-09-12 2016-09-12 Acid-alpha glucosidase variants and uses thereof
PCT/EP2017/072945 WO2018046775A1 (en) 2016-09-12 2017-09-12 Acid-alpha glucosidase variants and uses thereof

Publications (1)

Publication Number Publication Date
PL3510049T3 true PL3510049T3 (pl) 2024-08-19

Family

ID=56990394

Family Applications (1)

Application Number Title Priority Date Filing Date
PL17768082.4T PL3510049T3 (pl) 2016-09-12 2017-09-12 Warianty kwaśnej alfa glukozydazy i ich zastosowania

Country Status (23)

Country Link
US (3) US20190390224A1 (pl)
EP (3) EP3293203A1 (pl)
JP (2) JP7601554B2 (pl)
KR (2) KR20230049763A (pl)
CN (2) CN109843930B (pl)
AU (2) AU2017322377B2 (pl)
BR (1) BR112019004783A2 (pl)
CA (1) CA3036368A1 (pl)
CL (1) CL2019000610A1 (pl)
CO (1) CO2019002248A2 (pl)
DK (1) DK3510049T5 (pl)
ES (1) ES2970293T3 (pl)
FI (1) FI3510049T3 (pl)
IL (2) IL265170B2 (pl)
MX (2) MX2019002841A (pl)
MY (1) MY205583A (pl)
PE (2) PE20241128A1 (pl)
PH (1) PH12019500376A1 (pl)
PL (1) PL3510049T3 (pl)
PT (1) PT3510049T (pl)
SG (1) SG11201901430WA (pl)
WO (1) WO2018046775A1 (pl)
ZA (1) ZA201902140B (pl)

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GB201508026D0 (en) 2015-05-11 2015-06-24 Ucl Business Plc Capsid
EP3293259A1 (en) 2016-09-12 2018-03-14 Genethon Acid-alpha glucosidase variants and uses thereof
PE20191203A1 (es) 2016-09-12 2019-09-10 Genethon Variantes de alfa-glucosidasa acida y usos de las mismas
ES3065816T3 (en) 2017-06-07 2026-05-08 Regeneron Pharma Compositions and methods for internalizing enzymes
CN112040985A (zh) 2018-02-07 2020-12-04 瑞泽恩制药公司 用于递送治疗性蛋白质的方法和组合物
CN112334489A (zh) * 2018-05-16 2021-02-05 星火治疗有限公司 密码子优化的酸性α-葡萄糖苷酶表达盒及其使用方法
BR112020023145A2 (pt) 2018-05-17 2021-02-02 Regeneron Pharmaceuticals, Inc. anticorpo anti-cd63 ou fragmento de ligação ao antígeno do mesmo, molécula de ligação ao antígeno biespecífica, proteína terapêutica de múltiplos domínios, polinucleotídeo composição farmacêutica, e, composto
US12018087B2 (en) 2018-08-02 2024-06-25 Dyne Therapeutics, Inc. Muscle-targeting complexes comprising an anti-transferrin receptor antibody linked to an oligonucleotide and methods of delivering oligonucleotide to a subject
US12290574B2 (en) 2018-08-24 2025-05-06 Spark Therapeutics, Inc. Optimized promoter sequences, intron-free expression constructs and methods of use
US20220162640A1 (en) 2019-04-08 2022-05-26 Genethon Hybrid promoters for muscle expression
JP7771045B2 (ja) 2019-07-09 2025-11-17 ジェネトン 糖原病(gsd)の処置
CN114555808A (zh) 2019-10-22 2022-05-27 吉尼松公司 嵌合多肽及其用途
WO2021078834A1 (en) 2019-10-22 2021-04-29 Genethon Chimeric acid-alpha glucosidase polypeptides and uses thereof
PE20221266A1 (es) * 2019-12-20 2022-08-16 Codexis Inc Variantes de alfa-glucosidasa acida disenadas por ingenieria
EP3913060A1 (en) * 2020-05-22 2021-11-24 Genethon Vectors encoding a glucose-6-phosphatase (g6pase-a) for gene therapy
CN117897492A (zh) 2021-08-04 2024-04-16 吉尼松公司 用于肌肉和cns中的基因表达的杂合启动子

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6858425B1 (en) 1998-12-04 2005-02-22 Genzyme Corporation Human acid alpha glucosidase gene and bovine alpha-S1 casein gene sequences
CA2353522A1 (en) 1998-12-07 2000-06-15 Pharming Intellectual Property B.V. Treatment of pompe's disease
US7629309B2 (en) * 2002-05-29 2009-12-08 Zystor Therapeutics, Inc. Targeted therapeutic proteins
JP5433133B2 (ja) 2003-01-22 2014-03-05 デューク・ユニヴァーシティ リソソームポリペプチドを発現するための改善された構築物
CA2553955C (en) * 2004-02-10 2012-08-28 Zystor Therapeutics, Inc. Acid alpha-glucosidase and fragments thereof
US8633006B2 (en) * 2004-06-29 2014-01-21 Novozymes, Inc. Polypeptides having alpha-glucosidase activity and polynucleotides encoding same
BRPI0511764B8 (pt) 2004-06-01 2021-05-25 Avigen Inc método de prevenção de agregação de vírions de vírus adeno-associado recombinante (raav) em uma preparação purificada de virions raav
US9050333B2 (en) 2008-07-08 2015-06-09 Duke University Method of treating glycogen storage disease type III with human acid α-glucosidase
AU2010366066B2 (en) * 2010-12-22 2016-01-14 Fondazione Telethon Therapeutic strategies to treat CNS pathology in mucopolysaccharidoses
RU2013151875A (ru) 2011-04-22 2015-05-27 Джензим Корпорейшн Модифицированная кислая альфа глюкозидаза с ускоренным процессингом
WO2013013017A2 (en) * 2011-07-21 2013-01-24 Alnylam Pharmaceuticals, Inc. Compositions and methods for modifying the glycosylation of lysosomal storage disorder therapeutics
WO2013177533A1 (en) * 2012-05-25 2013-11-28 California Institute Of Technology Expression of secreted and cell-surface polypeptides
PT3024498T (pt) 2013-07-22 2020-03-06 Childrens Hospital Philadelphia Variante aav e composições, métodos e usos para transferência genética em células, órgãos e tecidos
CA3205555A1 (en) 2014-04-25 2015-10-29 Genethon Treatment of hyperbilirubinemia
WO2015192092A1 (en) * 2014-06-13 2015-12-17 Valerion Therapeutics, Llc Methods and compositions for treatment of glycogen storage diseases and glycogen metabolism disorders
WO2015196179A1 (en) 2014-06-20 2015-12-23 University Of Florida Research Foundation, Inc. Methods of packaging multiple adeno-associated virus vectors
EP3220958A1 (en) * 2014-10-24 2017-09-27 Shire Human Genetic Therapies, Inc. Lysosomal targeting of enzymes, and uses thereof

Also Published As

Publication number Publication date
AU2017322377A1 (en) 2019-03-28
DK3510049T5 (da) 2024-09-02
JP2022180543A (ja) 2022-12-06
US20210040503A1 (en) 2021-02-11
EP3293203A1 (en) 2018-03-14
IL265170B1 (en) 2023-06-01
CN109843930B (zh) 2023-11-17
EP3510049B8 (en) 2023-12-20
CN117512014A (zh) 2024-02-06
ZA201902140B (en) 2024-12-18
MX2024004419A (es) 2024-05-03
US20240043867A1 (en) 2024-02-08
IL265170B2 (en) 2023-10-01
EP3510049A1 (en) 2019-07-17
AU2017322377B2 (en) 2024-05-16
FI3510049T3 (fi) 2024-02-02
PH12019500376A1 (en) 2019-05-15
IL265170A (en) 2019-05-30
DK3510049T3 (da) 2024-01-29
US20190390224A1 (en) 2019-12-26
JP7601554B2 (ja) 2024-12-17
BR112019004783A2 (pt) 2019-06-04
SG11201901430WA (en) 2019-03-28
PE20241128A1 (es) 2024-05-24
RU2019110772A (ru) 2020-10-12
EP3510049B1 (en) 2023-11-08
MX2019002841A (es) 2019-08-29
KR20230049763A (ko) 2023-04-13
CA3036368A1 (en) 2018-03-15
PT3510049T (pt) 2024-01-30
IL302354B1 (en) 2024-05-01
RU2019110772A3 (pl) 2020-11-25
IL302354A (en) 2023-06-01
ES2970293T3 (es) 2024-05-27
IL302354B2 (en) 2024-09-01
WO2018046775A1 (en) 2018-03-15
CN109843930A (zh) 2019-06-04
AU2024205629A1 (en) 2024-08-29
CO2019002248A2 (es) 2019-05-21
EP4361178A2 (en) 2024-05-01
CL2019000610A1 (es) 2019-07-05
PE20190802A1 (es) 2019-06-10
JP2019533991A (ja) 2019-11-28
JP7667122B2 (ja) 2025-04-22
KR20190056388A (ko) 2019-05-24
MY205583A (en) 2024-10-28
EP4361178A3 (en) 2024-07-17

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