CN106604635B - 具有人源化程序性细胞死亡1基因的非人动物 - Google Patents

具有人源化程序性细胞死亡1基因的非人动物 Download PDF

Info

Publication number
CN106604635B
CN106604635B CN201580033075.2A CN201580033075A CN106604635B CN 106604635 B CN106604635 B CN 106604635B CN 201580033075 A CN201580033075 A CN 201580033075A CN 106604635 B CN106604635 B CN 106604635B
Authority
CN
China
Prior art keywords
human
rodent
humanized
endogenous
gene
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
CN201580033075.2A
Other languages
English (en)
Chinese (zh)
Other versions
CN106604635A (zh
Inventor
E·布罗瓦
A·O·穆吉卡
K-M·V·赖
A·J·莫菲
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 CN201911291579.0A priority Critical patent/CN110923256B/zh
Publication of CN106604635A publication Critical patent/CN106604635A/zh
Application granted granted Critical
Publication of CN106604635B publication Critical patent/CN106604635B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
    • A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4747—Apoptosis related proteins
    • 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
    • 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
    • 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
    • C07K14/70521—CD28, CD152
    • 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
    • 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
    • C07K16/2818—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 CD28 or CD152
    • 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
    • C07K16/2827—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 B7 molecules, e.g. CD80, CD86
    • 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
    • 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
    • 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
    • C12N5/0603—Embryonic cells ; Embryoid bodies
    • C12N5/0606—Pluripotent embryonic cells, e.g. embryonic stem cells [ES]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • 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
    • G01N33/502—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 non-proliferative effects
    • G01N33/5038—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 non-proliferative effects involving detection of metabolites per se
    • 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
    • A01K2207/15—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
    • A01K2217/07—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
    • 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
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
    • 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
    • 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
    • C07K2317/30—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
    • 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
    • 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
    • C07K2319/03—Fusion polypeptide containing a localisation/targetting motif containing a transmembrane segment
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/52—Assays involving cytokines
    • G01N2333/555—Interferons [IFN]
    • G01N2333/57—IFN-gamma
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70503—Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
    • 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)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Immunology (AREA)
  • General Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biophysics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Toxicology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Wood Science & Technology (AREA)
  • Environmental Sciences (AREA)
  • Microbiology (AREA)
  • Cell Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • General Engineering & Computer Science (AREA)
  • Pathology (AREA)
  • Urology & Nephrology (AREA)
  • Physics & Mathematics (AREA)
  • Public Health (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Animal Husbandry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Endocrinology (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Tropical Medicine & Parasitology (AREA)
CN201580033075.2A 2014-06-19 2015-06-19 具有人源化程序性细胞死亡1基因的非人动物 Active CN106604635B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201911291579.0A CN110923256B (zh) 2014-06-19 2015-06-19 具有人源化程序性细胞死亡1基因的非人动物

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US201462014181P 2014-06-19 2014-06-19
US62/014,181 2014-06-19
US201462086518P 2014-12-02 2014-12-02
US62/086,518 2014-12-02
US201562138221P 2015-03-25 2015-03-25
US62/138,221 2015-03-25
PCT/US2015/036649 WO2015196051A1 (en) 2014-06-19 2015-06-19 Non-human animals having a humanized programmed cell death 1 gene

Related Child Applications (1)

Application Number Title Priority Date Filing Date
CN201911291579.0A Division CN110923256B (zh) 2014-06-19 2015-06-19 具有人源化程序性细胞死亡1基因的非人动物

Publications (2)

Publication Number Publication Date
CN106604635A CN106604635A (zh) 2017-04-26
CN106604635B true CN106604635B (zh) 2020-01-14

Family

ID=53546709

Family Applications (2)

Application Number Title Priority Date Filing Date
CN201580033075.2A Active CN106604635B (zh) 2014-06-19 2015-06-19 具有人源化程序性细胞死亡1基因的非人动物
CN201911291579.0A Active CN110923256B (zh) 2014-06-19 2015-06-19 具有人源化程序性细胞死亡1基因的非人动物

Family Applications After (1)

Application Number Title Priority Date Filing Date
CN201911291579.0A Active CN110923256B (zh) 2014-06-19 2015-06-19 具有人源化程序性细胞死亡1基因的非人动物

Country Status (24)

Country Link
US (4) US10390522B2 (OSRAM)
EP (2) EP3157956B1 (OSRAM)
JP (3) JP6904707B2 (OSRAM)
KR (2) KR102482295B1 (OSRAM)
CN (2) CN106604635B (OSRAM)
AU (2) AU2015276978B2 (OSRAM)
BR (1) BR112016029650A2 (OSRAM)
CA (1) CA2951278A1 (OSRAM)
CY (1) CY1122940T1 (OSRAM)
DK (1) DK3157956T3 (OSRAM)
ES (1) ES2783424T3 (OSRAM)
HR (1) HRP20200613T1 (OSRAM)
HU (1) HUE048677T2 (OSRAM)
IL (2) IL287519B2 (OSRAM)
LT (1) LT3157956T (OSRAM)
MX (1) MX2016016903A (OSRAM)
PL (1) PL3157956T3 (OSRAM)
PT (1) PT3157956T (OSRAM)
RS (1) RS60097B1 (OSRAM)
RU (1) RU2735958C2 (OSRAM)
SG (2) SG11201609638RA (OSRAM)
SI (1) SI3157956T1 (OSRAM)
SM (1) SMT202000184T1 (OSRAM)
WO (1) WO2015196051A1 (OSRAM)

Families Citing this family (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8307177B2 (en) 2008-09-05 2012-11-06 Commvault Systems, Inc. Systems and methods for management of virtualization data
HRP20170908T1 (hr) 2008-12-09 2017-09-22 F. Hoffmann - La Roche Ag Protutijela anti-pd-l1 i njihova uporaba za poboljšanje funkcije t-stanice
US9461881B2 (en) 2011-09-30 2016-10-04 Commvault Systems, Inc. Migration of existing computing systems to cloud computing sites or virtual machines
US20140181044A1 (en) 2012-12-21 2014-06-26 Commvault Systems, Inc. Systems and methods to identify uncharacterized and unprotected virtual machines
US9378035B2 (en) 2012-12-28 2016-06-28 Commvault Systems, Inc. Systems and methods for repurposing virtual machines
HRP20210122T1 (hr) 2013-05-02 2021-04-16 Anaptysbio, Inc. Protutijela usmjerena protiv programirane smrti-1 (pd-1)
RS60097B1 (sr) * 2014-06-19 2020-05-29 Regeneron Pharma Ne-humane životinje koje imaju humanizovani gen za programiranu ćelijsku smrt 1
CA2967823A1 (en) 2014-11-24 2016-06-02 Regeneron Pharmaceuticals, Inc. Non-human animals expressing humanized cd3 complex
SMT201900178T1 (it) 2014-12-05 2019-05-10 Regeneron Pharma Animali diversi dall’uomo aventi un gruppo umanizzato del gene 47 di differenziazione
IL282649B (en) * 2014-12-09 2022-07-01 Regeneron Pharma Non-human animals with a humanized gene for differentiation cluster 274
US9563514B2 (en) 2015-06-19 2017-02-07 Commvault Systems, Inc. Assignment of proxies for virtual-machine secondary copy operations including streaming backup jobs
US10084873B2 (en) 2015-06-19 2018-09-25 Commvault Systems, Inc. Assignment of data agent proxies for executing virtual-machine secondary copy operations including streaming backup jobs
JP7014706B2 (ja) 2015-07-13 2022-02-01 サイトメックス セラピューティクス インコーポレイテッド 抗ｐｄ－１抗体、活性化可能抗ｐｄ－１抗体、およびその使用方法
PL3376857T3 (pl) 2015-11-20 2021-09-13 Regeneron Pharmaceuticals, Inc. Zwierzęta inne niż człowiek posiadające humanizowany gen aktywacji limfocytów 3
CN108779159B (zh) 2016-02-04 2022-12-30 瑞泽恩制药公司 具有经改造的angptl8基因的非人动物
EP3422845B1 (en) 2016-02-29 2021-06-02 Regeneron Pharmaceuticals, Inc. Rodents having a humanized tmprss gene
TWI822521B (zh) 2016-05-13 2023-11-11 美商再生元醫藥公司 藉由投予pd-1抑制劑治療皮膚癌之方法
WO2017200796A1 (en) * 2016-05-17 2017-11-23 Albert Einstein College Of Medicine, Inc. Engineered pd-1 variants
PT3462853T (pt) * 2016-06-03 2023-04-21 Regeneron Pharma Animais não humanos que expressam desoxinucleotidiltransferase terminal exógena
DK3476865T5 (da) 2016-06-28 2024-09-09 Biocytogen Pharmaceuticals Beijing Co Ltd Fremgangsmåde til konstruktion af pd-1-gen-modificeret humaniseret dyremodel og anvendelse deraf
WO2018041118A1 (en) * 2016-08-31 2018-03-08 Beijing Biocytogen Co., Ltd Genetically modified non-human animal with human or chimeric pd-l1
CN107815466B (zh) 2016-08-31 2020-03-13 百奥赛图江苏基因生物技术有限公司 人源化基因改造动物模型的制备方法及应用
WO2018085468A1 (en) 2016-11-01 2018-05-11 Anaptysbio, Inc. Antibodies directed against programmed death- 1 (pd-1)
CN107828722B (zh) * 2016-11-04 2021-07-23 北京泰盛生物科技有限公司 特异性表达pd-1的干细胞、其鉴定和分离方法及用途
MA46952A (fr) * 2016-12-01 2019-10-09 Regeneron Pharma Anticorps anti-pd-l1 radiomarqués pour imagerie immuno-pet
US11407830B2 (en) 2017-01-09 2022-08-09 Tesaro, Inc. Methods of treating cancer with anti-PD-1 antibodies
EP3585812A1 (en) 2017-02-21 2020-01-01 Regeneron Pharmaceuticals, Inc. Anti-pd-1 antibodies for treatment of lung cancer
US10949308B2 (en) 2017-03-15 2021-03-16 Commvault Systems, Inc. Application aware backup of virtual machines
US10853195B2 (en) 2017-03-31 2020-12-01 Commvault Systems, Inc. Granular restoration of virtual machine application data
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
CN109136275B (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gitr基因改造动物模型的制备方法及应用
CN109136274B (zh) 2017-06-19 2021-04-23 百奥赛图江苏基因生物技术有限公司 人源化cd40基因改造动物模型的制备方法及应用
CN109280674B (zh) * 2017-07-21 2020-12-01 北京百奥赛图基因生物技术有限公司 一种筛选抗体的非人模式动物的构建方法及其应用
BR112020003609A2 (pt) * 2017-09-29 2020-09-01 Regeneron Pharmaceuticals, Inc. sistema e método para formar uma emulsão
CN109666701B (zh) * 2017-10-13 2021-08-24 百奥赛图(北京)医药科技股份有限公司 一种pd-1基因修饰人源化动物模型的构建方法及其应用
WO2019072241A1 (en) * 2017-10-13 2019-04-18 Beijing Biocytogen Co., Ltd NON-HUMAN ANIMAL GENETICALLY MODIFIED WITH PD-1 HUMAN OR CHIMERIC
CN116064611A (zh) 2017-11-30 2023-05-05 瑞泽恩制药公司 包含人源化trkb基因座的非人动物
CN116420679B (zh) 2018-03-26 2025-10-03 瑞泽恩制药公司 用于测试治疗剂的人源化啮齿动物
WO2020018511A1 (en) 2018-07-16 2020-01-23 Regeneron Pharmaceuticals, Inc. Non-human animal models of ditra disease and uses thereof
CN109266656B (zh) * 2018-10-10 2021-02-19 江苏集萃药康生物科技股份有限公司 一种PD1人源化BALB/c小鼠模型的构建方法及其应用
CN109452229B (zh) * 2018-11-19 2021-10-22 百奥赛图(北京)医药科技股份有限公司 狗源化pd-1基因改造动物模型的制备方法及应用
US20220272953A1 (en) * 2019-07-29 2022-09-01 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Genetically modified non-human animal with human or chimeric il33
EP4096396A1 (en) * 2020-01-28 2022-12-07 Regeneron Pharmaceuticals, Inc. Non-human animals comprising a humanized pnpla3 locus and methods of use
US11656951B2 (en) 2020-10-28 2023-05-23 Commvault Systems, Inc. Data loss vulnerability detection
TW202400232A (zh) 2022-03-16 2024-01-01 日商第一三共股份有限公司 多特異性分子與免疫檢查點抑制劑之組合
WO2024002259A1 (zh) * 2022-06-29 2024-01-04 百奥赛图(北京)医药科技股份有限公司 一种osm、osmr、il31ra和/或il31基因修饰的非人动物

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012050451A (ja) * 2003-12-24 2012-03-15 G2 Inflammation Pty Ltd ヒトまたはヒト化Ｃ５ａＲをコードするポリヌクレオチドを含むトランスジェニック非ヒト哺乳動物

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2143491C (en) 1994-03-01 2011-02-22 Yasumasa Ishida A novel peptide related to human programmed cell death and dna encoding it
US5670356A (en) 1994-12-12 1997-09-23 Promega Corporation Modified luciferase
US5874304A (en) 1996-01-18 1999-02-23 University Of Florida Research Foundation, Inc. Humanized green fluorescent protein genes and methods
AU7309601A (en) 2000-06-28 2002-01-08 Genetics Inst Pd-l2 molecules: novel pd-1 ligands and uses therefor
US6586251B2 (en) 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
AU2002224037A1 (en) 2000-11-15 2002-05-27 Tasuku Honjo Pd-1-lacking mouse and use thereof
US20040033497A1 (en) 2002-08-13 2004-02-19 Alarcon-Riquelme Marta E. Polymorphisms of PD-1
WO2004056875A1 (en) 2002-12-23 2004-07-08 Wyeth Antibodies against pd-1 and uses therefor
WO2005060739A1 (en) 2003-12-24 2005-07-07 G2 Inflammation Pty Ltd Transgenic non-human mammal comprising a polynucleotide encoding human or humanized c5ar
PT2767161T (pt) 2004-10-19 2018-04-20 Regeneron Pharma Método para gerar um animal homozigótico para uma modificação genética
DK2161336T4 (en) * 2005-05-09 2017-04-24 Ono Pharmaceutical Co Human monoclonal antibodies for programmed death 1 (PD-1) and methods for treating cancer using anti-PD-1 antibodies alone or in combination with other immunotherapies
EP3214095B1 (en) 2005-05-12 2019-12-11 ZymoGenetics, Inc. Compositions and methods for modulating immune responses
BRPI0611766A2 (pt) * 2005-06-08 2011-12-20 Dana Farber Cancer Inst Inc métodos e composições para o tratamento de infecções persistentes e cáncer por inibição da rota de morte celular programada
HRP20170908T1 (hr) 2008-12-09 2017-09-22 F. Hoffmann - La Roche Ag Protutijela anti-pd-l1 i njihova uporaba za poboljšanje funkcije t-stanice
RU2425880C2 (ru) * 2009-07-30 2011-08-10 Учреждение Российской академии наук Институт общей генетики им. Н.И. Вавилова РАН Способ получения трансгенных мышей
WO2011020005A1 (en) 2009-08-14 2011-02-17 Regeneron Pharmaceuticals, Inc. miRNA-REGULATED DIFFERENTIATION-DEPENDENT SELF-DELETING CASSETTE
TW201134488A (en) * 2010-03-11 2011-10-16 Ucb Pharma Sa PD-1 antibodies
US8871996B2 (en) * 2010-06-09 2014-10-28 Regeneron Pharmaceuticals, Inc. Mice expressing human voltage-gated sodium channels
RS55949B1 (sr) * 2011-10-28 2017-09-29 Regeneron Pharmaeuticals Inc Humanizovani il-6 i il-6 receptor
SMT202200205T1 (it) 2011-10-28 2022-07-21 Regeneron Pharma Topi geneticamente modificati che esprimono molecole chimeriche del complesso maggiore di istocompatibilità (mhc) ii
ES2858978T3 (es) 2011-10-28 2021-09-30 Regeneron Pharma Ratones con receptores de linfocitos T genéticamente modificados
AU2012324016C1 (en) 2011-10-28 2018-02-15 Regeneron Pharmaceuticals, Inc. Genetically modified major histocompatibility complex mice
KR102402806B1 (ko) 2012-11-05 2022-05-30 리제너론 파마슈티칼스 인코포레이티드 유전자 변형된 비-인간 동물 및 그것의 사용 방법
CA2900832A1 (en) 2013-02-20 2014-08-28 Regeneron Pharmaceuticals, Inc. Mice expressing humanized t-cell co-receptors
WO2014130667A1 (en) 2013-02-22 2014-08-28 Regeneron Pharmaceuticals, Inc. Mice expressing humanized major histocompatibility complex
LT3175706T (lt) 2013-09-23 2019-02-25 Regeneron Pharmaceuticals, Inc. Gyvūnai, išskyrus žmogų, turintys humanizuotą signalą reguliuojančio baltymo geną
WO2015077071A1 (en) 2013-11-19 2015-05-28 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized b-cell activating factor gene
KR102439412B1 (ko) 2014-04-08 2022-09-02 리제너론 파아마슈티컬스, 인크. 인간화된 Fc-감마 수용체를 갖는 비-인간 동물
NO2785538T3 (OSRAM) 2014-05-07 2018-08-04
RU2711744C1 (ru) 2014-05-19 2020-01-21 Ридженерон Фармасьютикалз, Инк. Генетически модифицированные животные, отличные от человека, экспрессирующие epo человека
RS60097B1 (sr) * 2014-06-19 2020-05-29 Regeneron Pharma Ne-humane životinje koje imaju humanizovani gen za programiranu ćelijsku smrt 1

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2012050451A (ja) * 2003-12-24 2012-03-15 G2 Inflammation Pty Ltd ヒトまたはヒト化Ｃ５ａＲをコードするポリヌクレオチドを含むトランスジェニック非ヒト哺乳動物

Also Published As

Publication number Publication date
US20240298619A1 (en) 2024-09-12
ES2783424T3 (es) 2020-09-17
JP6904707B2 (ja) 2021-07-21
IL287519A (en) 2021-12-01
US20150366174A1 (en) 2015-12-24
RU2735958C2 (ru) 2020-11-11
IL249145A0 (en) 2017-01-31
MX2016016903A (es) 2017-03-27
EP3157956A1 (en) 2017-04-26
US11684050B2 (en) 2023-06-27
LT3157956T (lt) 2020-05-11
WO2015196051A1 (en) 2015-12-23
AU2021203100A1 (en) 2021-06-10
JP2021094035A (ja) 2021-06-24
EP3683238A1 (en) 2020-07-22
AU2021203100B2 (en) 2024-10-10
CY1122940T1 (el) 2021-10-29
CN110923256B (zh) 2025-03-11
SMT202000184T1 (it) 2020-05-08
AU2015276978A1 (en) 2016-12-22
RU2016149434A (ru) 2018-07-19
KR102594863B1 (ko) 2023-10-27
KR102482295B1 (ko) 2022-12-30
EP3157956B1 (en) 2020-02-05
JP2017521060A (ja) 2017-08-03
CN110923256A (zh) 2020-03-27
KR20170020365A (ko) 2017-02-22
PL3157956T3 (pl) 2020-06-29
NZ727157A (en) 2023-08-25
HUE048677T2 (hu) 2020-07-28
IL287519B2 (en) 2024-01-01
SI3157956T1 (sl) 2020-06-30
PT3157956T (pt) 2020-04-09
BR112016029650A2 (pt) 2017-10-24
SG11201609638RA (en) 2016-12-29
NZ765428A (en) 2024-09-27
DK3157956T3 (da) 2020-04-27
CN106604635A (zh) 2017-04-26
KR20230003455A (ko) 2023-01-05
CA2951278A1 (en) 2015-12-23
US10390522B2 (en) 2019-08-27
AU2015276978B2 (en) 2021-02-25
RS60097B1 (sr) 2020-05-29
HRP20200613T1 (hr) 2020-07-10
JP2023083469A (ja) 2023-06-15
RU2016149434A3 (OSRAM) 2018-12-25
US20200053992A1 (en) 2020-02-20
SG10201811116UA (en) 2019-01-30
JP7720349B2 (ja) 2025-08-07
US20180206462A1 (en) 2018-07-26
IL287519B1 (en) 2023-09-01
JP7612475B2 (ja) 2025-01-14
IL249145B (en) 2021-12-01

Similar Documents

Publication Publication Date Title
US20240298619A1 (en) Non-human animals having a humanized programmed cell death 1 gene
US12089575B2 (en) Genetically modified mouse that expresses humanized PD1 and PD-L1 proteins
HK40108429A (en) Non-human animals having a humanized cluster of differentiation 274 gene
HK40023109A (en) Non-human animals having a humanized programmed cell death 1 gene
HK40040582A (en) Non-human animals having a humanized cluster of differentiation 274 gene
HK1231084B (en) Non-human animals having a humanized programmed cell death 1 gene
HK1231084A1 (en) Non-human animals having a humanized programmed cell death 1 gene
HK1238254B (en) Non-human animals having a humanized cluster of differentiation 274 gene
HK1238254A1 (en) Non-human animals having a humanized cluster of differentiation 274 gene

Legal Events

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