HRP20192255T1 - Humanizirani miševi s univerzalnim lakim lancem - Google Patents

Humanizirani miševi s univerzalnim lakim lancem Download PDF

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HRP20192255T1
HRP20192255T1 HRP20192255TT HRP20192255T HRP20192255T1 HR P20192255 T1 HRP20192255 T1 HR P20192255T1 HR P20192255T T HRP20192255T T HR P20192255TT HR P20192255 T HRP20192255 T HR P20192255T HR P20192255 T1 HRP20192255 T1 HR P20192255T1
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functional
light chain
segment
endogenous
mouse
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HRP20192255TT
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English (en)
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John Mcwhirter
Lynn Macdonald
Sean Stevens
Samuel Davis
David R. Buckler
Karolina A. Hosiawa
Andrew J. Murphy
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Regeneron Pharmaceuticals, Inc.
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Publication of HRP20192255T1 publication Critical patent/HRP20192255T1/hr

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
    • C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
    • C07K16/2833—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against MHC-molecules, e.g. HLA-molecules
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • 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)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6489—Metalloendopeptidases (3.4.24)
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/15—Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/01—Animal expressing industrially exogenous proteins
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
    • C07K2317/515—Complete light chain, i.e. VL + CL
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
    • C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
    • C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/30—Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
    • 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
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/20—Pseudochromosomes, minichrosomosomes
    • C12N2800/204—Pseudochromosomes, minichrosomosomes of bacterial origin, e.g. BAC
    • 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
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/30—Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Immunology (AREA)
  • Biophysics (AREA)
  • General Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Environmental Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Microbiology (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Husbandry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Physics & Mathematics (AREA)
  • Plant Pathology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Pyrane Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Claims (7)

1. Miš čiji genom sadrži: (a) varijabilni lokus humaniziranog imunoglobulinskog lakog lanca koji sadrži najmanje jedan nepreuređeni humani segment VH, najmanje jedan nepreuređeni humani segment DH i najmanje jedan nepreuređeni humani segment JH operativno povezan s endogenim genom konstantne regije teškog lanca; (b) varijabilni lokus humaniziranog imunoglobulinskog lakog lanca koji ne sadrži više od jedne ili više od dvije humane sekvence preuređenog lakog lanca V/J operativno povezane s endogenim genom konstantne regije lakog lanca; i (c) ektopijsku sekvencu nukleinske kiseline koja izražava funkcionalni mišji protein ADAM6a ili njegov funkcionalni ortolog ili funkcionalni homolog ili funkcionalni fragment i ektopijsku sekvencu nukleinske kiseline koja izražava funkcionalni mišji protein ADAM6b ili njegov funkcionalni ortolog ili funkcionalni homolog ili funkcionalni fragment, pri čemu su proteini ADAM6, ortolozi, homolozi ili fragmenti funkcionalni u mužjaku miša, naznačeno time, što je spomenuta funkcija povezana s plodnošću mužjaka, pri čemu je kod spomenutog miša eliminirana ili smanjena funkcija endogenog ADAM6 i koji je dodatno karakteriziran time što u svojoj zametnoj liniji ne sadrži nepreuređeni endogeni imunoglobulinski segment gena Vκ i nepreuređeni endogeni imunoglobulinski segment gena Jκ.
2. Miš prema patentnom zahtjevu 1, naznačen time, što se ektopijske sekvence nukleinske kiseline nalaze na lokusu koji nije varijabilni lokus imunoglobulinskog lakog lanca.
3. Miš čiji genom sadrži: varijabilni lokus humaniziranog imunoglobulinskog lakog lanca koji sadrži najmanje jedan nepreuređeni humani segment VH, najmanje jedan nepreuređeni humani segment DH i najmanje jedan nepreuređeni humani segment JH operativno povezan s endogenim genom konstantne regije teškog lanca; varijabilni lokus humaniziranog imunoglobulinskog lakog lanca koji sadrži jednu sekvencu preuređenog humanog lakog lanca V/J operativno povezanu s endogenim genom konstantne regije lakog lanca, naznačeno time, što miš izražava kimerni jedan laki lanac i naznačeno time, što miš iz ektopijskih sekvenci nukleinske kiseline izražava funkcionalni mišji protein ADAM6a i funkcionalni mišji protein ADAM6b, pri čemu su proteini ADAM6a i ADAM6b funkcionalni u mužjaku miša, naznačeno time, što je spomenuta funkcija povezana s plodnošću mužjaka, pri čemu je kod spomenutog miša eliminirana ili smanjena funkcija endogenog ADAM6 i koji je dodatno karakteriziran time što u svojoj zametnoj liniji ne sadrži nepreuređeni endogeni imunoglobulinski segment gena Vκ i nepreuređeni endogeni imunoglobulinski segment gena Jκ.
4. Miš prema patentnom zahtjevu 3, naznačen time, što se ektopijske sekvence nukleinske kiseline nalaze na položaju koji nije unutar endogenog lokusa imunoglobulinskog teškog lanca.
5. Mišja stanica čiji genom sadrži: varijabilni lokus humaniziranog imunoglobulinskog lakog lanca koji sadrži najmanje jedan nepreuređeni humani segment VH, najmanje jedan nepreuređeni humani segment DH i najmanje jedan nepreuređeni humani segment JH operativno povezan s endogenim genom konstantne regije teškog lanca; varijabilni lokus humaniziranog imunoglobulinskog lakog lanca koji ne sadrži više od jedne ili više od dvije humane sekvence preuređenog lakog lanca V/J operativno povezane s endogenim genom konstantne regije lakog lanca; i ektopijsku sekvencu nukleinske kiseline koja izražava funkcionalni mišji protein ADAM6a ili njegov funkcionalni ortolog ili funkcionalni homolog ili funkcionalni fragment i ektopijsku sekvencu nukleinske kiseline koja izražava funkcionalni mišji protein ADAM6b ili njegov funkcionalni ortolog ili funkcionalni homolog ili funkcionalni fragment, pri čemu su proteini ADAM6, ortolozi, homolozi ili fragmenti funkcionalni u mužjaku miša, naznačeno time, što je spomenuta funkcija povezana s plodnošću mužjaka, pri čemu je kod spomenute stanice eliminirana ili smanjena funkcija endogenog ADAM6 i koja je dodatno karakterizirana time što ne sadrži nepreuređeni endogeni imunoglobulinski segment gena Vκ i nepreuređeni endogeni imunoglobulinski segment gena Jκ.
6. Mišja stanica prema patentnom zahtjevu 5, naznačena time, što mišja stanica sadrži jednu sekvencu preuređenog humanog lakog lanca V/J.
7. Mišja stanica prema bilo kojem patentnom zahtjevu 5 ili 6, naznačena time, što je stanica embrionalna matična stanica.
HRP20192255TT 2011-08-05 2019-12-16 Humanizirani miševi s univerzalnim lakim lancem HRP20192255T1 (hr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161515374P 2011-08-05 2011-08-05
PCT/US2012/049600 WO2013022782A1 (en) 2011-08-05 2012-08-03 Humanized universal light chain mice
EP12746246.3A EP2739740B1 (en) 2011-08-05 2012-08-03 Humanized universal light chain mice

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HRP20192255T1 true HRP20192255T1 (hr) 2020-03-06

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HRP20210916TT HRP20210916T1 (hr) 2011-08-05 2021-06-09 Miševi s ljudskim univerzalnim lakim lancem

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US (3) US10130081B2 (hr)
EP (3) EP3865581B1 (hr)
JP (7) JP6510234B2 (hr)
CN (2) CN103917650B (hr)
AU (5) AU2012294624B2 (hr)
BR (1) BR112014002713B1 (hr)
CA (1) CA2844070A1 (hr)
CY (2) CY1122435T1 (hr)
DK (2) DK2739740T3 (hr)
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HR (2) HRP20192255T1 (hr)
HU (2) HUE047278T2 (hr)
IL (4) IL273982B2 (hr)
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NZ (4) NZ781020A (hr)
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