CN105592695B - 具有人源化信号调节蛋白基因的非人动物 - Google Patents

具有人源化信号调节蛋白基因的非人动物 Download PDF

Info

Publication number
CN105592695B
CN105592695B CN201480051997.1A CN201480051997A CN105592695B CN 105592695 B CN105592695 B CN 105592695B CN 201480051997 A CN201480051997 A CN 201480051997A CN 105592695 B CN105592695 B CN 105592695B
Authority
CN
China
Prior art keywords
sirp
mouse
genes
albumen
humanization
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
CN201480051997.1A
Other languages
English (en)
Chinese (zh)
Other versions
CN105592695A (zh
Inventor
A·J·墨菲
O·G·瑟斯顿
B·瓦尔盖斯
C·居雷尔
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Regeneron Pharmaceuticals Inc
Original Assignee
Regeneron Pharmaceuticals 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 Regeneron Pharmaceuticals Inc filed Critical Regeneron Pharmaceuticals Inc
Priority to CN201810267662.3A priority Critical patent/CN108441497B/zh
Publication of CN105592695A publication Critical patent/CN105592695A/zh
Application granted granted Critical
Publication of CN105592695B publication Critical patent/CN105592695B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/0004—Screening or testing of compounds for diagnosis of disorders, assessment of conditions, e.g. renal clearance, gastric emptying, testing for diabetes, allergy, rheuma, pancreas functions
    • A61K49/0008—Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
    • 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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70596—Molecules with a "CD"-designation not provided for elsewhere
    • 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
    • C07K16/2809—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 the T-cell receptor (TcR)-CD3 complex
    • 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
    • C07K16/2887—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against CD20
    • 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
    • C12N15/8509—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
    • 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
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/89—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microinjection
    • 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
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/90—Stable introduction of foreign DNA into chromosome
    • C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
    • C12N15/907—Stable introduction of foreign DNA into chromosome using homologous recombination in mammalian 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/16—Hydrolases (3) acting on ester bonds (3.1)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5011—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics for testing antineoplastic activity
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5008—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics
    • G01N33/5082—Supracellular entities, e.g. tissue, organisms
    • G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
    • 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
    • A01K2207/12—Animals modified by administration of exogenous cells
    • 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
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • 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
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A01K2217/052—Animals comprising random inserted nucleic acids (transgenic) inducing gain of function
    • 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
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A01K2217/054—Animals comprising random inserted nucleic acids (transgenic) inducing loss of function
    • 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
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • 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
    • 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
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/0331—Animal model for proliferative diseases
    • 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
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/035—Animal model for multifactorial diseases
    • A01K2267/0381—Animal model for diseases of the hematopoietic system
    • 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
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/035—Animal model for multifactorial diseases
    • A01K2267/0387—Animal model for diseases of the immune system
    • 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
    • C07K14/705—Receptors; Cell surface antigens; Cell surface determinants
    • C07K14/70503—Immunoglobulin superfamily
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2317/00—Immunoglobulins specific features
    • C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
    • C07K2317/31—Immunoglobulins specific features characterized by aspects of specificity or valency multispecific
    • 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
    • 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
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/90—Stable introduction of foreign DNA into chromosome
    • C12N15/902—Stable introduction of foreign DNA into chromosome using homologous recombination
    • 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
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • C12N2015/8518—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic expressing industrially exogenous proteins, e.g. for pharmaceutical use, human insulin, blood factors, immunoglobulins, pseudoparticles
    • 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
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • C12N2015/8527—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic for producing animal models, e.g. for tests or diseases
    • 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
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • C12N2015/8527—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic for producing animal models, e.g. for tests or diseases
    • C12N2015/8572—Animal models for proliferative diseases, e.g. comprising an oncogene
    • 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
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y301/00—Hydrolases acting on ester bonds (3.1)
    • C12Y301/03—Phosphoric monoester hydrolases (3.1.3)
    • C12Y301/03048—Protein-tyrosine-phosphatase (3.1.3.48)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/04—Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value
    • G01N2500/10—Screening for compounds of potential therapeutic value involving cells

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Organic Chemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Urology & Nephrology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Cell Biology (AREA)
  • Toxicology (AREA)
  • Plant Pathology (AREA)
  • Hematology (AREA)
  • Environmental Sciences (AREA)
  • Pathology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Husbandry (AREA)
  • Rheumatology (AREA)
  • Epidemiology (AREA)
  • Public Health (AREA)
CN201480051997.1A 2013-09-23 2014-09-23 具有人源化信号调节蛋白基因的非人动物 Active CN105592695B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201810267662.3A CN108441497B (zh) 2013-09-23 2014-09-23 具有人源化信号调节蛋白基因的非人动物

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361881261P 2013-09-23 2013-09-23
US61/881,261 2013-09-23
PCT/US2014/056910 WO2015042557A1 (en) 2013-09-23 2014-09-23 Non-human animals having a humanized signal-regulatory protein gene

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN201810267662.3A Division CN108441497B (zh) 2013-09-23 2014-09-23 具有人源化信号调节蛋白基因的非人动物

Publications (2)

Publication Number Publication Date
CN105592695A CN105592695A (zh) 2016-05-18
CN105592695B true CN105592695B (zh) 2018-04-10

Family

ID=51663510

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201480051997.1A Active CN105592695B (zh) 2013-09-23 2014-09-23 具有人源化信号调节蛋白基因的非人动物
CN201810267662.3A Active CN108441497B (zh) 2013-09-23 2014-09-23 具有人源化信号调节蛋白基因的非人动物

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN201810267662.3A Active CN108441497B (zh) 2013-09-23 2014-09-23 具有人源化信号调节蛋白基因的非人动物

Country Status (28)

Country Link
US (9) US9193977B2 (cg-RX-API-DMAC7.html)
EP (5) EP3434101B1 (cg-RX-API-DMAC7.html)
JP (4) JP6453893B2 (cg-RX-API-DMAC7.html)
KR (2) KR102370419B1 (cg-RX-API-DMAC7.html)
CN (2) CN105592695B (cg-RX-API-DMAC7.html)
AU (3) AU2014321187B2 (cg-RX-API-DMAC7.html)
CA (1) CA2925564C (cg-RX-API-DMAC7.html)
CY (1) CY1121410T1 (cg-RX-API-DMAC7.html)
DK (4) DK4269430T3 (cg-RX-API-DMAC7.html)
ES (4) ES3037239T3 (cg-RX-API-DMAC7.html)
FI (2) FI4269430T3 (cg-RX-API-DMAC7.html)
HR (3) HRP20251062T1 (cg-RX-API-DMAC7.html)
HU (3) HUE042412T2 (cg-RX-API-DMAC7.html)
IL (4) IL297607B2 (cg-RX-API-DMAC7.html)
LT (3) LT3175706T (cg-RX-API-DMAC7.html)
MX (1) MX368931B (cg-RX-API-DMAC7.html)
NZ (1) NZ717817A (cg-RX-API-DMAC7.html)
PH (1) PH12016500342A1 (cg-RX-API-DMAC7.html)
PL (3) PL4269430T3 (cg-RX-API-DMAC7.html)
PT (4) PT2922394T (cg-RX-API-DMAC7.html)
RS (3) RS67091B1 (cg-RX-API-DMAC7.html)
RU (2) RU2671166C2 (cg-RX-API-DMAC7.html)
SG (3) SG11201601184UA (cg-RX-API-DMAC7.html)
SI (3) SI3434101T1 (cg-RX-API-DMAC7.html)
SM (3) SMT202300287T1 (cg-RX-API-DMAC7.html)
TR (1) TR201901782T4 (cg-RX-API-DMAC7.html)
WO (1) WO2015042557A1 (cg-RX-API-DMAC7.html)
ZA (1) ZA201601138B (cg-RX-API-DMAC7.html)

Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK3417701T3 (da) 2009-10-06 2022-03-14 Regeneron Pharma Genmodificerede mus og indpodning
MX338971B (es) 2011-02-15 2016-05-06 Inst Res Biomedicine Irb Ratones de m-csf humanizada.
CN120718856A (zh) 2012-09-07 2025-09-30 再生元制药公司 经遗传修饰的非人动物及其使用方法
ES2748662T3 (es) 2012-11-05 2020-03-17 Institute For Res In Biomedicine Irb Roedores inmunodeficientes modificados genéticamente y métodos de uso de los mismos
DK4269430T3 (da) * 2013-09-23 2025-08-18 Regeneron Pharma Ikke-menneskelige dyr, der har et humaniseret signalregulerende proteingen
SI3138397T1 (sl) 2013-10-15 2019-04-30 Regeneron Pharmaceuticals, Inc. Humanizirane živali IL-15
MY183188A (en) 2013-11-19 2021-02-18 Regeneron Pharma Non-human animals having a humanized b-cell activating factor gene
ES2794942T3 (es) 2014-04-08 2020-11-19 Regeneron Pharma Animales no humanos que tienen receptores Fc-gamma humanizados
NO2785538T3 (cg-RX-API-DMAC7.html) 2014-05-07 2018-08-04
EP4306648A3 (en) 2014-05-19 2024-04-17 Regeneron Pharmaceuticals, Inc. Genetically modified mice expressing human epo
WO2015196051A1 (en) 2014-06-19 2015-12-23 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized programmed cell death 1 gene
RS63410B1 (sr) 2014-11-24 2022-08-31 Regeneron Pharma Ne-humane životinje koje eksprimiraju humanizovani cd3 kompleks
BR112017010490A2 (pt) 2014-12-05 2018-04-03 Regeneron Pharma roedor, polipeptídeo cd47, célula ou tecido de roedor isolado, célula-tronco emprionária de roedor, embrião de roedor, e, métodos de produzir um roedor, de fornecimento de um roedor, de enxerto de células humanas em um roedor, de avaliação de eficácia terapêutica de uma droga direcionada a células humanas e de avaliar as propriedades farmacocinéticas, de avaliar a toxicidade específica e inespecífica de uma droga direcionada ao cd47 humano.
LT3230320T (lt) 2014-12-09 2021-01-11 Regeneron Pharmaceuticals, Inc. Gyvūnai, išskyrus žmogų, turintys humanizuotą diferenciacijos klasterio 274 geną
PT3282835T (pt) 2015-04-13 2023-07-25 Univ Yale Ratinhos knockin de sirpa-il15 humanizadas e métodos de utilização dos mesmos
CN104904661B (zh) * 2015-06-05 2018-07-24 杭州正因生物技术有限公司 一种人源化小鼠
RS62151B1 (sr) 2015-08-07 2021-08-31 Alx Oncology Inc Konstrukti koji sadrže sirp-alfa domen ili njegovu varijantu
LT3376857T (lt) 2015-11-20 2021-06-25 Regeneron Pharmaceuticals, Inc. Gyvūnai, ne žmonės, turintys humanizuotą limfocitų aktyvavimo geną
CA3012693C (en) 2016-02-04 2022-08-23 Regeneron Pharmaceuticals, Inc. Non-human animals having an engineered angptl8 gene
CN109068621B (zh) 2016-02-29 2021-07-20 再生元制药公司 具有人源化的tmprss基因的啮齿类动物
CN108467873B (zh) 2017-03-17 2020-03-13 百奥赛图江苏基因生物技术有限公司 一种cd132基因缺失的免疫缺陷动物模型的制备方法及应用
CN108588126B (zh) 2017-03-31 2020-04-10 北京百奥赛图基因生物技术有限公司 Cd47基因人源化改造动物模型的制备方法及应用
WO2018177441A1 (en) * 2017-03-31 2018-10-04 Beijing Biocytogen Co., Ltd GENETICALLY MODIFIED NON-HUMAN ANIMAL WITH HUMAN OR CHIMERIC SIRPα
WO2018233608A1 (en) * 2017-06-19 2018-12-27 Beijing Biocytogen Co., Ltd Genetically modified non-human animal with human or chimeric cd28
CN109136261B (zh) 2017-06-19 2021-03-16 百奥赛图(北京)医药科技股份有限公司 人源化cd28基因改造动物模型的制备方法及应用
US11021719B2 (en) 2017-07-31 2021-06-01 Regeneron Pharmaceuticals, Inc. Methods and compositions for assessing CRISPER/Cas-mediated disruption or excision and CRISPR/Cas-induced recombination with an exogenous donor nucleic acid in vivo
ES3033963T3 (en) 2017-07-31 2025-08-11 Regeneron Pharma Method of testing the ability of a crispr/cas9 nuclease to modify a target genomic locus in vivo, by making use of a cas-transgenic mouse or rat which comprises a cas9 expression cassette in its genome
WO2019067875A1 (en) * 2017-09-29 2019-04-04 Regeneron Pharmaceuticals, Inc. NON-HUMAN ANIMALS COMPRISING A HUMANIZED TTR LOCUS AND METHODS OF USE
AU2018375796B2 (en) 2017-11-30 2024-11-21 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized TRKB locus
WO2019183123A1 (en) 2018-03-19 2019-09-26 Regeneron Pharmaceuticals, Inc. Transcription modulation in animals using crispr/cas systems
AU2019242586B2 (en) 2018-03-26 2025-09-11 Regeneron Pharmaceuticals, Inc. Humanized rodents for testing therapeutic agents
SG11202012338QA (en) 2018-07-10 2021-01-28 Univ Kobe Nat Univ Corp ANTI-SIRPa ANTIBODY
PL3823443T3 (pl) 2018-07-16 2024-09-23 Regeneron Pharmaceuticals, Inc. Modele gryzoni z chorobą ditra i ich zastosowania
US12331320B2 (en) 2018-10-10 2025-06-17 The Research Foundation For The State University Of New York Genome edited cancer cell vaccines
WO2020160285A1 (en) * 2019-02-01 2020-08-06 The Board Of Trustees Of The Leland Stanford Junior University SIRPα EXPRESSION ON T CELLS IS A BIOMARKER FOR FUNCTIONAL T CELLS DURING EXHAUSTION
IL286905B2 (en) 2019-04-04 2024-06-01 Regeneron Pharma Non-human animals containing the human coagulation factor 12 locus
EP3976099A1 (en) 2019-05-31 2022-04-06 ALX Oncology Inc. Methods of treating cancer with sirp alpha fc fusion in combination with an immune checkpoint inhibitor
WO2020247452A1 (en) 2019-06-04 2020-12-10 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized ttr locus with a beta-slip mutation and methods of use
SG11202111256XA (en) 2019-06-07 2021-11-29 Regeneron Pharma Non-human animals comprising a humanized albumin locus
WO2021136537A1 (en) * 2019-12-31 2021-07-08 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. GENETICALLY MODIFIED IMMUNODEFICIENT NON-HUMAN ANIMAL WITH HUMAN OR CHIMERIC SIRPα/CD47
US12250931B2 (en) 2020-01-28 2025-03-18 Regeneron Pharmaceuticals, Inc. Genetically modified mouse with a humanized PNPLA3 gene and methods of use
EP4138550A1 (en) 2020-04-21 2023-03-01 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized cxcl13 gene
WO2022140221A1 (en) 2020-12-21 2022-06-30 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized tslp gene, a humanized tslp receptor gene, and/or a humanized il7ra gene
IL308400A (en) 2021-05-13 2024-01-01 Alx Oncology Inc Combined therapies for cancer treatment
US20250143272A1 (en) * 2022-01-25 2025-05-08 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Genetically modified non-human animal with human or chimeric nkp46
CA3260622A1 (en) 2022-07-19 2024-01-25 Regeneron Pharmaceuticals, Inc. GENETICALLY MODIFIED ANIMAL MODEL AND ITS USE TO MODEL THE HUMAN IMMUNE SYSTEM
US20240224964A9 (en) 2022-09-29 2024-07-11 Regeneron Pharmaceuticals, Inc. Correction of hepatosteatosis in humanized liver animals through restoration of il6/il6r/gp130 signaling in human hepatocytes
US20240415103A1 (en) 2023-06-16 2024-12-19 Regeneron Pharmaceuticals, Inc. Vectors, genetically modified cells, and genetically modified non-human animals comprising the same
US20250255282A1 (en) 2024-02-08 2025-08-14 Regeneron Pharmaceuticals, Inc. Vectors, genetically modified cells, and genetically modified non-human animals comprising the same
WO2025212991A1 (en) 2024-04-05 2025-10-09 Regeneron Pharmaceuticals, Inc. Rodent models of disease
WO2025250495A1 (en) 2024-05-28 2025-12-04 Regeneron Pharmaceuticals, Inc. Acceleration of human hepatocyte engraftment in humanized liver animals by supplementing paracrine ligands or agonists that activate human liver regeneration signals

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012040207A2 (en) * 2010-09-20 2012-03-29 Yale University HUMAM SIRPAα TRANSGENIC ANIMALS AND THEIR METHODS OF USE
WO2013063556A1 (en) * 2011-10-28 2013-05-02 Regeneron Pharmaceuticals, Inc. Humanized il-6 and il-6 receptor
CN103492576A (zh) * 2011-02-14 2014-01-01 雷维维科公司 用于血管化异种移植物及其衍生物的异种移植的遗传修饰的猪

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5149635A (en) 1986-09-12 1992-09-22 Abbott Biotech, Inc. Messenger RNA stabilization in animal cells
CA2303615A1 (en) 1997-09-12 1999-03-18 Jurg Tschopp April- a novel protein with growth effects
US6586251B2 (en) 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
ES2364335T3 (es) * 2003-12-24 2011-08-31 G2 Inflammation Pty Ltd Mamífero no humano transgénico que comprende un polinucleótido que codifica el c5ar humano o humanizado.
PL1802193T3 (pl) 2004-10-19 2014-09-30 Regeneron Pharma Sposób wytwarzania myszy homozygotycznej pod względem modyfikacji genetycznej
US20060272038A1 (en) 2005-05-27 2006-11-30 Michael De Vivo Transgenic Alzheimer's mouse model vectors and uses thereof
US20070028316A1 (en) 2005-06-02 2007-02-01 Xiaoxia Li Transgenic non-human Act1-deficient mammals and uses thereof
US20100239578A1 (en) * 2007-10-11 2010-09-23 University Health Network Modulation of sirp-alpha - cd47 interaction for increasing human hematopoietic stem cell engraftment and compounds therefor
EP2262898B1 (en) 2008-03-07 2018-01-24 Regeneron Pharmaceuticals, Inc. Es cell-derived mice from diploid host embryo injection
RU2425880C2 (ru) * 2009-07-30 2011-08-10 Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН Способ получения трансгенных мышей
DK3417701T3 (da) 2009-10-06 2022-03-14 Regeneron Pharma Genmodificerede mus og indpodning
MX338971B (es) 2011-02-15 2016-05-06 Inst Res Biomedicine Irb Ratones de m-csf humanizada.
LT3262932T (lt) 2011-10-28 2019-08-26 Regeneron Pharmaceuticals, Inc. Pelės su genetiškai modifikuotu pagrindiniu histosuderinamumo kompleksu
LT3590332T (lt) 2011-10-28 2022-08-10 Regeneron Pharmaceuticals, Inc. Genetiškai modifikuotos pelės, ekspresuojančios chimerines pagrindinio audinių dermės komplekso (mhc) ii molekules
US8962913B2 (en) 2012-06-18 2015-02-24 Regeneron Pharmaceuticals, Inc. Humanized IL-7 rodents
CN120718856A (zh) 2012-09-07 2025-09-30 再生元制药公司 经遗传修饰的非人动物及其使用方法
ES2748662T3 (es) 2012-11-05 2020-03-17 Institute For Res In Biomedicine Irb Roedores inmunodeficientes modificados genéticamente y métodos de uso de los mismos
SMT201900429T1 (it) 2013-02-20 2019-09-09 Regeneron Pharma Topi esprimenti co-recettori umanizzati linfociti t
EP2958937B1 (en) 2013-02-22 2018-08-15 Regeneron Pharmaceuticals, Inc. Mice expressing humanized major histocompatibility complex
DK4269430T3 (da) 2013-09-23 2025-08-18 Regeneron Pharma Ikke-menneskelige dyr, der har et humaniseret signalregulerende proteingen
CA2984413A1 (en) 2015-04-30 2016-11-03 Institute Of Immunology Co., Ltd. Transgenic non-human animal expressing human specific molecule and human fc.gamma. receptor family

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012040207A2 (en) * 2010-09-20 2012-03-29 Yale University HUMAM SIRPAα TRANSGENIC ANIMALS AND THEIR METHODS OF USE
CN103492576A (zh) * 2011-02-14 2014-01-01 雷维维科公司 用于血管化异种移植物及其衍生物的异种移植的遗传修饰的猪
WO2013063556A1 (en) * 2011-10-28 2013-05-02 Regeneron Pharmaceuticals, Inc. Humanized il-6 and il-6 receptor

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
high-throughput engineering of the mouse genome coupled with high-resolution expression analysis;valenzuela et al;《nature biotech》;20030630;第21卷(第6期);652-659，822 *
transgenic expression of human signal regulatory mice improves engraftment of human hematopoietic cells in humanized ice supplemntary online data;till strowig et al;《proceedings of the national academy of sciences》;20110809;第108卷(第32期);13218-13223 *

Also Published As

Publication number Publication date
LT3434101T (lt) 2023-09-25
SMT202300287T1 (it) 2023-11-13
LT4269430T (lt) 2025-08-25
KR20160056900A (ko) 2016-05-20
US12161097B2 (en) 2024-12-10
IL244187A0 (en) 2016-04-21
US10206379B2 (en) 2019-02-19
RS58365B1 (sr) 2019-03-29
SG11201601184UA (en) 2016-03-30
MX2016003636A (es) 2016-07-21
ES2959333T3 (es) 2024-02-23
JP2019047818A (ja) 2019-03-28
PH12016500342A1 (en) 2016-05-02
CN105592695A (zh) 2016-05-18
CA2925564A1 (en) 2015-03-26
EP4635977A2 (en) 2025-10-22
US20190124895A1 (en) 2019-05-02
JP6453893B2 (ja) 2019-01-16
ES3037239T3 (en) 2025-09-30
PT4269430T (pt) 2025-08-06
CN108441497B (zh) 2021-10-29
SMT201900067T1 (it) 2019-02-28
JP2020114209A (ja) 2020-07-30
IL278679A (en) 2022-12-01
IL297607B2 (en) 2024-01-01
JP6665269B2 (ja) 2020-03-13
HK1209275A1 (en) 2016-04-01
EP2922394A1 (en) 2015-09-30
WO2015042557A1 (en) 2015-03-26
AU2020286187B2 (en) 2024-06-13
IL297607B1 (en) 2023-09-01
EP4269430A3 (en) 2024-01-10
KR20220032125A (ko) 2022-03-15
HRP20251062T1 (hr) 2025-11-07
ES2624614T3 (es) 2017-07-17
WO2015042557A4 (en) 2015-06-18
EP3175706A1 (en) 2017-06-07
AU2020286187A1 (en) 2021-01-07
DK3434101T3 (da) 2023-10-02
AU2024216527A1 (en) 2024-09-19
US20180139941A1 (en) 2018-05-24
EP3434101A1 (en) 2019-01-30
IL262958A (en) 2018-12-31
JP2016537015A (ja) 2016-12-01
PT2922394T (pt) 2017-05-22
KR102407354B1 (ko) 2022-06-10
ES2710282T3 (es) 2019-04-24
PL4269430T3 (pl) 2025-10-13
RU2016110462A (ru) 2017-10-30
EP3175706B1 (en) 2018-11-07
SI3434101T1 (sl) 2023-11-30
RU2671166C2 (ru) 2018-10-29
RU2016110462A3 (cg-RX-API-DMAC7.html) 2018-03-30
RS67091B1 (sr) 2025-09-30
US20210251201A1 (en) 2021-08-19
RU2018136614A (ru) 2018-11-27
LT3175706T (lt) 2019-02-25
US9901083B2 (en) 2018-02-27
PT3434101T (pt) 2023-09-19
EP4269430A2 (en) 2023-11-01
DK3434101T5 (da) 2024-09-16
IL278679B2 (en) 2023-04-01
JP6875573B2 (ja) 2021-05-26
HUE042412T2 (hu) 2019-06-28
PT3175706T (pt) 2019-02-11
AU2014321187B2 (en) 2020-09-17
RS64573B1 (sr) 2023-10-31
JP7149370B2 (ja) 2022-10-06
HRP20190227T1 (hr) 2019-06-14
EP2922394B1 (en) 2017-02-22
MX368931B (es) 2019-10-22
HRP20231121T1 (hr) 2023-12-22
US9462794B2 (en) 2016-10-11
US20150089679A1 (en) 2015-03-26
SG10201801326PA (en) 2018-03-28
HUE063376T2 (hu) 2024-01-28
DK4269430T3 (da) 2025-08-18
ZA201601138B (en) 2020-06-24
DK3175706T3 (en) 2019-03-04
SI4269430T1 (sl) 2025-09-30
US20160374321A1 (en) 2016-12-29
US20200187468A1 (en) 2020-06-18
DK2922394T3 (en) 2017-05-15
PL3175706T3 (pl) 2019-05-31
EP3434101B1 (en) 2023-08-16
KR102370419B1 (ko) 2022-03-04
SG10201902547SA (en) 2019-04-29
PL3434101T3 (pl) 2024-02-19
US9193977B2 (en) 2015-11-24
FI4269430T3 (fi) 2025-08-08
JP2021104064A (ja) 2021-07-26
HUE072332T2 (hu) 2025-11-28
NZ717817A (en) 2022-07-01
US20160050896A1 (en) 2016-02-25
CN108441497A (zh) 2018-08-24
US10426146B2 (en) 2019-10-01
SMT202500280T1 (it) 2025-09-12
TR201901782T4 (tr) 2019-03-21
US9127292B2 (en) 2015-09-08
IL244187B (en) 2018-11-29
US11019810B2 (en) 2021-06-01
CA2925564C (en) 2023-03-21
US9700027B2 (en) 2017-07-11
CY1121410T1 (el) 2020-05-29
US20150089678A1 (en) 2015-03-26
FI3434101T3 (fi) 2023-10-02
EP4269430B1 (en) 2025-06-18
IL297607A (en) 2022-12-01
SI3175706T1 (sl) 2019-03-29
US20170265442A1 (en) 2017-09-21

Similar Documents

Publication Publication Date Title
JP7149370B2 (ja) ヒト化シグナル調節タンパク質遺伝子を有する非ヒト動物
AU2014321187A1 (en) Non-human animals having a humanized signal-regulatory protein gene
HK40093188A (en) Non-human animals having a humanized signal-regulatory protein gene
HK40093188B (en) Non-human animals having a humanized signal-regulatory protein gene
HK1259923B (en) Non-human animals having a humanized signal-regulatory protein gene
HK1234601A1 (en) Non-human animals having a humanized signal-regulatory protein gene
HK1234601B (en) Non-human animals having a humanized signal-regulatory protein gene
HK1259923A1 (en) Non-human animals having a humanized signal-regulatory protein gene
HK1209275B (en) Non-human animals having a humanized signal-regulatory protein gene

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant