JP2022533438A - 改変ウイルス粒子およびその使用 - Google Patents

改変ウイルス粒子およびその使用 Download PDF

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Publication number
JP2022533438A
JP2022533438A JP2021569402A JP2021569402A JP2022533438A JP 2022533438 A JP2022533438 A JP 2022533438A JP 2021569402 A JP2021569402 A JP 2021569402A JP 2021569402 A JP2021569402 A JP 2021569402A JP 2022533438 A JP2022533438 A JP 2022533438A
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JP
Japan
Prior art keywords
aav
protein
amino acid
capsid protein
acid sequence
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Pending
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JP2021569402A
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Japanese (ja)
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JPWO2020242984A5 (enExample
Inventor
リア サビン，
クリストス カラツオス，
スヴェン モーラー－タンク，
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Regeneron Pharmaceuticals Inc
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Regeneron Pharmaceuticals Inc
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Publication of JP2022533438A publication Critical patent/JP2022533438A/ja
Publication of JPWO2020242984A5 publication Critical patent/JPWO2020242984A5/ja
Priority to JP2024196799A priority Critical patent/JP2025032110A/ja
Priority to JP2025085876A priority patent/JP2025119015A/ja
Pending legal-status Critical Current

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    • 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
    • A61K48/005—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/315—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Streptococcus (G), e.g. Enterococci
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • 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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • 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
    • C12N2750/14122—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • 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
    • C12N2750/14123—Virus like particles [VLP]
    • 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
    • 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
    • C12N2750/14145—Special targeting system for 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
    • 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
    • C12N2750/14151—Methods of production or purification of viral material
    • C12N2750/14152—Methods of production or purification of viral material relating to complementing cells and packaging systems for producing virus or viral particles

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Virology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Toxicology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
JP2021569402A 2019-05-24 2020-05-22 改変ウイルス粒子およびその使用 Pending JP2022533438A (ja)

Priority Applications (2)

Application Number Priority Date Filing Date Title
JP2024196799A JP2025032110A (ja) 2019-05-24 2024-11-11 改変ウイルス粒子およびその使用
JP2025085876A JP2025119015A (ja) 2019-05-24 2025-05-22 改変ウイルス粒子およびその使用

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201962852791P 2019-05-24 2019-05-24
US62/852,791 2019-05-24
PCT/US2020/034328 WO2020242984A1 (en) 2019-05-24 2020-05-22 Modified viral particles and uses thereof

Related Child Applications (1)

Application Number Title Priority Date Filing Date
JP2024196799A Division JP2025032110A (ja) 2019-05-24 2024-11-11 改変ウイルス粒子およびその使用

Publications (2)

Publication Number Publication Date
JP2022533438A true JP2022533438A (ja) 2022-07-22
JPWO2020242984A5 JPWO2020242984A5 (enExample) 2023-05-30

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JP2021569402A Pending JP2022533438A (ja) 2019-05-24 2020-05-22 改変ウイルス粒子およびその使用
JP2024196799A Pending JP2025032110A (ja) 2019-05-24 2024-11-11 改変ウイルス粒子およびその使用
JP2025085876A Pending JP2025119015A (ja) 2019-05-24 2025-05-22 改変ウイルス粒子およびその使用

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JP2024196799A Pending JP2025032110A (ja) 2019-05-24 2024-11-11 改変ウイルス粒子およびその使用
JP2025085876A Pending JP2025119015A (ja) 2019-05-24 2025-05-22 改変ウイルス粒子およびその使用

Country Status (19)

Country Link
US (1) US20220241430A1 (enExample)
EP (1) EP3976631A1 (enExample)
JP (3) JP2022533438A (enExample)
KR (1) KR20220011664A (enExample)
CN (2) CN114989267A (enExample)
AR (2) AR118997A1 (enExample)
AU (1) AU2020283537A1 (enExample)
BR (1) BR112021023692A2 (enExample)
CA (1) CA3140386A1 (enExample)
CL (2) CL2021003096A1 (enExample)
CO (1) CO2021017692A2 (enExample)
IL (1) IL288233A (enExample)
MA (1) MA56035A (enExample)
MX (1) MX2021014338A (enExample)
PE (1) PE20212357A1 (enExample)
PH (1) PH12021552887A1 (enExample)
SG (1) SG11202112917PA (enExample)
TW (1) TW202110869A (enExample)
WO (1) WO2020242984A1 (enExample)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2019227910B2 (en) 2018-02-28 2025-07-17 The Regents Of The University Of California A modular system for gene and protein delivery based on AAV
KR20220011664A (ko) * 2019-05-24 2022-01-28 리제너론 파마슈티칼스 인코포레이티드 변형된 바이러스 입자 및 이의 용도
WO2022187377A1 (en) * 2021-03-02 2022-09-09 University Of Pittsburgh - Of The Commonwealth System Of Higher Education Adeno-associated viruses and methods and materials for making and using adeno-associated viruses
WO2022232575A1 (en) * 2021-04-30 2022-11-03 Duke University Compositions comprising adeno-associated virus chimera capsid proteins and methods of using the same
CA3222914A1 (en) * 2021-06-23 2022-12-29 Dyno Therapeutics, Inc. Capsid variants and methods of using the same
CA3256953A1 (en) 2022-05-09 2023-11-16 Regeneron Pharmaceuticals, Inc. VECTORS AND METHODS FOR IN VIVO ANTIBODY PRODUCTION
EP4536836A1 (en) 2022-06-07 2025-04-16 Regeneron Pharmaceuticals, Inc. Pseudotyped viral particles for targeting tcr-expressing cells
WO2025042462A2 (en) * 2023-08-24 2025-02-27 Ohio State Innovation Foundation Assays and methods for quality control of genome packaging for gene therapy
WO2025054526A1 (en) * 2023-09-07 2025-03-13 Regeneron Pharmaceuticals, Inc. Production and purification of covalently surface modified adeno-associated virus
WO2025111473A1 (en) * 2023-11-21 2025-05-30 Regeneron Pharmaceuticals, Inc. Covalently surface modified adeno-associated virus production by in vitro conjugation, and purification of covalently surface modified adeno-associated virus

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002516092A (ja) * 1998-05-28 2002-06-04 アメリカ合衆国 Ａａｖ５ベクターおよびその使用
WO2015191508A1 (en) * 2014-06-09 2015-12-17 Voyager Therapeutics, Inc. Chimeric capsids
WO2019006046A2 (en) * 2017-06-27 2019-01-03 Regeneron Pharmaceuticals, Inc. RECOMBINANT VIRAL PARTICLES WITH MODIFIED TROPISM AND USES THEREOF FOR TARGETED INTRODUCTION OF GENETIC MATERIAL INTO HUMAN CELLS
JP2019001805A (ja) * 2013-03-15 2019-01-10 ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル 二重グリカン結合性ａａｖベクターのための方法および組成物

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997005266A1 (en) 1995-07-25 1997-02-13 Introgene B.V. Methods and means for targeted gene delivery
AU4645697A (en) 1996-09-11 1998-04-02 Government Of The United States Of America, As Represented By The Secretary Of The Department Of Health And Human Services, The Aav4 vector and uses thereof
US6156303A (en) 1997-06-11 2000-12-05 University Of Washington Adeno-associated virus (AAV) isolates and AAV vectors derived therefrom
DK1127150T3 (da) 1998-11-05 2007-09-24 Univ Pennsylvania Nucleinsyresekvenser fra det adeno-associerede virus af serotype 1 samt vektorer og værtsceller, der indeholder disse
SG168422A1 (en) * 2001-11-13 2011-02-28 Univ Pennsylvania A method of detecting and/or identifying adeno-associated virus (aav) sequences and isolating novel sequences identified thereby
ES2602610T3 (es) 2007-05-31 2017-02-21 Medigene Ag Proteína estructural mutada de un parvovirus
MY172472A (en) 2009-12-10 2019-11-26 Regeneron Pharma Mice that make heavy chain antibodies
GB201002362D0 (en) 2010-02-11 2010-03-31 Isis Innovation Peptide tag systems that spontaneously form an irreversible link to protein partners via isopeptide bonds
ES2990174T3 (es) * 2014-03-10 2024-11-29 Uniqure Ip Bv Vectores de AAV mejorados producidos en células de insecto
BR112016021572A2 (pt) 2014-03-21 2017-10-03 Regeneron Pharma Métodos para preparar um animal não humano geneticamente modificado e para produzir proteínas de ligação, hibridoma, ácido nucleico, célula, e, proteína de ligação
SI3645551T1 (sl) 2017-06-27 2024-06-28 Regeneron Pharmaceuticals, Inc. S tropizmi spremenjeni rekombinantni virusni vektorji in njihova uporaba za tarčni vnos genetskega materiala v človeške celice
KR20220011664A (ko) * 2019-05-24 2022-01-28 리제너론 파마슈티칼스 인코포레이티드 변형된 바이러스 입자 및 이의 용도

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002516092A (ja) * 1998-05-28 2002-06-04 アメリカ合衆国 Ａａｖ５ベクターおよびその使用
JP2019001805A (ja) * 2013-03-15 2019-01-10 ザ・ユニヴァーシティ・オヴ・ノース・キャロライナ・アト・チャペル・ヒル 二重グリカン結合性ａａｖベクターのための方法および組成物
WO2015191508A1 (en) * 2014-06-09 2015-12-17 Voyager Therapeutics, Inc. Chimeric capsids
WO2019006046A2 (en) * 2017-06-27 2019-01-03 Regeneron Pharmaceuticals, Inc. RECOMBINANT VIRAL PARTICLES WITH MODIFIED TROPISM AND USES THEREOF FOR TARGETED INTRODUCTION OF GENETIC MATERIAL INTO HUMAN CELLS

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
JOURNAL OF VIROLOGY, vol. 77, no. 12, JPN5022009488, 2003, pages 6799 - 6810, ISSN: 0005501048 *
JOURNAL OF VIROLOGY, vol. 78, no. 12, JPN5022009487, 2004, pages 6509 - 6516, ISSN: 0005501047 *
JOURNAL OF VIROLOGY, vol. 82, no. 12, JPN6024017753, 2008, pages 5887 - 5911, ISSN: 0005501049 *

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Publication number Publication date
TW202110869A (zh) 2021-03-16
AR118997A1 (es) 2021-11-17
BR112021023692A2 (pt) 2022-01-04
CL2023000629A1 (es) 2023-10-20
CL2021003096A1 (es) 2022-09-20
EP3976631A1 (en) 2022-04-06
KR20220011664A (ko) 2022-01-28
US20220241430A1 (en) 2022-08-04
CN114989267A (zh) 2022-09-02
WO2020242984A9 (en) 2021-01-14
CN113874386A (zh) 2021-12-31
CA3140386A1 (en) 2020-12-03
MX2021014338A (es) 2022-01-06
CO2021017692A2 (es) 2022-01-17
PH12021552887A1 (en) 2022-09-05
SG11202112917PA (en) 2021-12-30
WO2020242984A1 (en) 2020-12-03
IL288233A (en) 2022-01-01
MA56035A (fr) 2022-04-06
AR124119A2 (es) 2023-02-15
JP2025032110A (ja) 2025-03-11
PE20212357A1 (es) 2021-12-17
JP2025119015A (ja) 2025-08-13
AU2020283537A1 (en) 2021-12-16

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