[go: up one dir, main page]
More Web Proxy on the site http://driver.im/

DK3434101T3 - Ikke-menneskelige dyr, der har et humaniseret signalregulerende proteingen - Google Patents

Ikke-menneskelige dyr, der har et humaniseret signalregulerende proteingen Download PDF

Info

Publication number
DK3434101T3
DK3434101T3 DK18192264.2T DK18192264T DK3434101T3 DK 3434101 T3 DK3434101 T3 DK 3434101T3 DK 18192264 T DK18192264 T DK 18192264T DK 3434101 T3 DK3434101 T3 DK 3434101T3
Authority
DK
Denmark
Prior art keywords
human animals
regulatory protein
signal regulatory
humanized
humanized signal
Prior art date
Application number
DK18192264.2T
Other languages
English (en)
Other versions
DK3434101T5 (da
Inventor
Andrew J Murphy
Gavin Thurston
Bindu Varghese
Cagen Gurer
Original Assignee
Regeneron Pharma
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 Pharma filed Critical Regeneron Pharma
Application granted granted Critical
Publication of DK3434101T3 publication Critical patent/DK3434101T3/da
Publication of DK3434101T5 publication Critical patent/DK3434101T5/da

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
    • 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
    • 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
    • C07K14/70503—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)
  • General Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Analytical Chemistry (AREA)
  • Animal Husbandry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Endocrinology (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
DK18192264.2T 2013-09-23 2014-09-23 Ikke-menneskelige dyr, der har et humaniseret signalregulerende proteingen DK3434101T5 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201361881261P 2013-09-23 2013-09-23
EP16206491.9A EP3175706B1 (en) 2013-09-23 2014-09-23 Non-human animals having a humanized signal-regulatory protein gene

Publications (2)

Publication Number Publication Date
DK3434101T3 true DK3434101T3 (da) 2023-10-02
DK3434101T5 DK3434101T5 (da) 2024-09-16

Family

ID=51663510

Family Applications (3)

Application Number Title Priority Date Filing Date
DK18192264.2T DK3434101T5 (da) 2013-09-23 2014-09-23 Ikke-menneskelige dyr, der har et humaniseret signalregulerende proteingen
DK16206491.9T DK3175706T3 (da) 2013-09-23 2014-09-23 Ikke-humane dyr med et humaniseret signal-regulatorisk proteingen
DK14781783.7T DK2922394T3 (da) 2013-09-23 2014-09-23 Ikke-humane dyr med et humaniseret signal-regulatorisk proteingen

Family Applications After (2)

Application Number Title Priority Date Filing Date
DK16206491.9T DK3175706T3 (da) 2013-09-23 2014-09-23 Ikke-humane dyr med et humaniseret signal-regulatorisk proteingen
DK14781783.7T DK2922394T3 (da) 2013-09-23 2014-09-23 Ikke-humane dyr med et humaniseret signal-regulatorisk proteingen

Country Status (28)

Country Link
US (9) US9193977B2 (da)
EP (4) EP4269430A3 (da)
JP (4) JP6453893B2 (da)
KR (2) KR102370419B1 (da)
CN (2) CN105592695B (da)
AU (3) AU2014321187B2 (da)
CA (1) CA2925564C (da)
CY (1) CY1121410T1 (da)
DK (3) DK3434101T5 (da)
ES (3) ES2710282T3 (da)
FI (1) FI3434101T3 (da)
HK (1) HK1209275A1 (da)
HR (2) HRP20231121T1 (da)
HU (2) HUE042412T2 (da)
IL (4) IL297607B2 (da)
LT (2) LT3175706T (da)
MX (1) MX368931B (da)
NZ (1) NZ717817A (da)
PH (1) PH12016500342A1 (da)
PL (2) PL3434101T3 (da)
PT (3) PT2922394T (da)
RS (2) RS64573B1 (da)
RU (2) RU2018136614A (da)
SG (3) SG11201601184UA (da)
SI (2) SI3434101T1 (da)
TR (1) TR201901782T4 (da)
WO (1) WO2015042557A1 (da)
ZA (1) ZA201601138B (da)

Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK3056082T3 (da) 2009-10-06 2018-12-17 Regeneron Pharma Genmodificerede mus og indpodning
SG10202008003VA (en) 2011-02-15 2020-10-29 Regeneron Pharma Humanized m-csf mice
FI2892330T3 (fi) 2012-09-07 2023-03-25 Univ Yale Geneettisesti muokattuja hiiriä ja menetelmiä niiden käyttämiseksi
KR102275412B1 (ko) 2012-11-05 2021-07-12 리제너론 파마슈티칼스 인코포레이티드 유전자 변형된 비-인간 동물 및 그것의 사용 방법
PL3434101T3 (pl) 2013-09-23 2024-02-19 Regeneron Pharmaceuticals, Inc. Zwierzęta inne niż ludzie posiadające humanizowany gen białka regulacji sygnału
US9155290B2 (en) 2013-10-15 2015-10-13 Regeneron Pharmaceuticals, Inc. Humanized IL-15 animals
MX356809B (es) 2013-11-19 2018-06-13 Regeneron Pharma Animales no humanos que tienen un gen del factor activador de celulas b.
EP3693383A1 (en) 2014-04-08 2020-08-12 Regeneron Pharmaceuticals, Inc. Mouse-human fc-gamma-ri proteins and encoding dna
NO2785538T3 (da) 2014-05-07 2018-08-04
PT3482629T (pt) 2014-05-19 2021-02-18 Univ Yale Animais não humanos geneticamente modificados que expressam epo humana
ES2783424T3 (es) 2014-06-19 2020-09-17 Regeneron Pharma Animales no humanos que tienen un gen de muerte celular programada 1 humanizado
RS61080B1 (sr) 2014-11-24 2020-12-31 Regeneron Pharma Ne-humane životinje koje eksprimiraju humanizovani cd3 kompleks
PT3850946T (pt) 2014-12-05 2024-01-02 Regeneron Pharma An:imais não romanos com tjm gene do grupo de diferenciação 47 romanizado
HRP20240855T1 (hr) 2014-12-09 2024-10-11 Regeneron Pharmaceuticals, Inc. Neljudske životinje koje imaju humanizirani gen cd274 iz diferencijacijske skupine
AU2016247892B2 (en) * 2015-04-13 2022-05-26 Institute For Research In Biomedicine (Irb) Humanized SIRPA-IL15 knockin mice and methods of use thereof
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
MX2018001428A (es) 2015-08-07 2018-09-05 Alx Oncology Inc Construcciones con un dominio sirp-alfa o sus variantes.
JP6997708B2 (ja) 2015-11-20 2022-02-04 リジェネロン・ファーマシューティカルズ・インコーポレイテッド ヒト化されたｌｙｍｐｈｏｃｙｔｅ－ａｃｔｉｖａｔｉｏｎ ｇｅｎｅ ３遺伝子を有する非ヒト動物
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
RU2749715C2 (ru) 2016-02-29 2021-06-16 Регенерон Фармасьютикалз, Инк. Грызуны, характеризующиеся гуманизированным геном tmprss
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 NON-HUMAN ANIMAL GENETICALLY MODIFIED TO CD28 HUMAN OR CHIMERIC
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
CA3068072A1 (en) 2017-07-31 2019-02-07 Regeneron Pharmaceuticals, Inc. Methods and compositions for assessing crispr/cas-mediated disruption or excision and crispr/cas-induced recombination with an exogenous donor nucleic acid in vivo
EP3585159A1 (en) 2017-07-31 2020-01-01 Regeneron Pharmaceuticals, Inc. Cas-transgenic mouse embryonic stem cells and mice and uses thereof
KR102544051B1 (ko) * 2017-09-29 2023-06-16 리제너론 파마슈티칼스 인코포레이티드 인간화된 ttr 유전자좌를 포함하는 비인간 동물 및 사용 방법
IL274740B2 (en) 2017-11-30 2024-06-01 Regeneron Pharma Non-human animals containing a human TRKB locus
AU2019239880B2 (en) 2018-03-19 2023-11-30 Regeneron Pharmaceuticals, Inc. Transcription modulation in animals using CRISPR/Cas systems
TW202431987A (zh) 2018-03-26 2024-08-16 美商再生元醫藥公司 用於測試治療藥劑之人類化囓齒動物
CN117024593A (zh) 2018-07-10 2023-11-10 国立大学法人神户大学 抗SIRPα抗体
HRP20240999T1 (hr) 2018-07-16 2024-10-25 Regeneron Pharmaceuticals, Inc. Glodavački modeli bolesti ditra i njihova upotreba
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
ES2966625T3 (es) 2019-04-04 2024-04-23 Regeneron Pharma Roedores que comprenden un locus del factor de coagulación 12 humanizado
CN114126648A (zh) 2019-05-31 2022-03-01 Alx肿瘤生物技术公司 用SIRPα Fc融合体组合免疫检查点抑制剂治疗癌症的方法
CN113874510A (zh) 2019-06-04 2021-12-31 瑞泽恩制药公司 包括具有β滑移突变的人源化TTR基因座的非人动物和使用方法
JP2022534560A (ja) 2019-06-07 2022-08-02 リジェネロン・ファーマシューティカルズ・インコーポレイテッド ヒト化アルブミン遺伝子座を含む非ヒト動物
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
US20230172170A1 (en) 2020-04-21 2023-06-08 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized cxcl13 gene
US20220192165A1 (en) 2020-12-21 2022-06-23 Regeneron Pharmaceuticals, Inc. Non-human animals having a humanized tslp gene, a humanized tslp receptor gene, and/or a humanized il7ra gene
US12098214B2 (en) 2021-05-13 2024-09-24 ALX Oncology Inc. Combination therapies for treating cancer
WO2023143341A1 (en) * 2022-01-25 2023-08-03 Biocytogen Pharmaceuticals (Beijing) Co., Ltd. Genetically modified non-human animal with human or chimeric nkp46
US20240102045A1 (en) 2022-07-19 2024-03-28 Regeneron Pharmaceuticals, Inc. Vectors, genetically modified cells, and genetically modified non-human animals comprising the same
WO2024073679A1 (en) 2022-09-29 2024-04-04 Regeneron Pharmaceuticals, Inc. Correction of hepatosteatosis in humanized liver animals through restoration of il6/il6r/gp130 signaling in human hepatocytes

Family Cites Families (24)

* 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
JP2001515712A (ja) * 1997-09-12 2001-09-25 バイオジェン インコーポレイテッド 増殖効果を有する新規タンパク質−ａｐｒｉｌ
US6586251B2 (en) 2000-10-31 2003-07-01 Regeneron Pharmaceuticals, Inc. Methods of modifying eukaryotic cells
ES2587344T3 (es) * 2003-12-24 2016-10-24 Novo Nordisk A/S Ratón transgénico que comprende un polinucleótido que codifica C5aR humano o humanizado
EP2767161B1 (en) 2004-10-19 2018-02-07 Regeneron Pharmaceuticals, Inc. Method for generating an non-human animal homozygous for a genetic modification
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
EP2388270A3 (en) * 2007-10-11 2012-04-25 The Hospital For Sick Children Modulation of SIRPa - CD47 interaction for increasing human hematopoietic stem cell engraftment and compounds therefor
WO2009114400A1 (en) 2008-03-07 2009-09-17 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
DK3056082T3 (da) 2009-10-06 2018-12-17 Regeneron Pharma Genmodificerede mus og indpodning
US9402377B2 (en) * 2010-09-20 2016-08-02 Yale University Human SIRPAalpha transgenic animals and their methods of use
AU2012217792A1 (en) * 2011-02-14 2013-08-29 Revivicor, Inc. Genetically modified pigs for xenotransplantation of vascularized xenografts and derivatives thereof
SG10202008003VA (en) * 2011-02-15 2020-10-29 Regeneron Pharma Humanized m-csf mice
RS59082B1 (sr) 2011-10-28 2019-09-30 Regeneron Pharma Miševi sa genetski modifikovanim glavnim kompleksom gena tkivne podudarnosti
EP4052572A1 (en) 2011-10-28 2022-09-07 Regeneron Pharmaceuticals, Inc. Genetically modified mice expressing chimeric major histocompatibility complex (mhc) ii molecules
RS55949B1 (sr) 2011-10-28 2017-09-29 Regeneron Pharmaeuticals Inc Humanizovani il-6 i il-6 receptor
US8962913B2 (en) 2012-06-18 2015-02-24 Regeneron Pharmaceuticals, Inc. Humanized IL-7 rodents
FI2892330T3 (fi) 2012-09-07 2023-03-25 Univ Yale Geneettisesti muokattuja hiiriä ja menetelmiä niiden käyttämiseksi
KR102275412B1 (ko) 2012-11-05 2021-07-12 리제너론 파마슈티칼스 인코포레이티드 유전자 변형된 비-인간 동물 및 그것의 사용 방법
US9848587B2 (en) 2013-02-20 2017-12-26 Regeneron Pharmaceuticals, Inc. Humanized T cell co-receptor mice
WO2014130667A1 (en) 2013-02-22 2014-08-28 Regeneron Pharmaceuticals, Inc. Mice expressing humanized major histocompatibility complex
PL3434101T3 (pl) 2013-09-23 2024-02-19 Regeneron Pharmaceuticals, Inc. Zwierzęta inne niż ludzie posiadające humanizowany gen białka regulacji sygnału
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

Also Published As

Publication number Publication date
EP3434101A1 (en) 2019-01-30
IL244187B (en) 2018-11-29
SI3175706T1 (sl) 2019-03-29
RU2018136614A (ru) 2018-11-27
US10206379B2 (en) 2019-02-19
CN108441497B (zh) 2021-10-29
CY1121410T1 (el) 2020-05-29
US9193977B2 (en) 2015-11-24
NZ717817A (en) 2022-07-01
ES2624614T3 (es) 2017-07-17
DK3434101T5 (da) 2024-09-16
HUE042412T2 (hu) 2019-06-28
IL297607B1 (en) 2023-09-01
JP2016537015A (ja) 2016-12-01
HUE063376T2 (hu) 2024-01-28
US20160050896A1 (en) 2016-02-25
US20180139941A1 (en) 2018-05-24
EP3175706B1 (en) 2018-11-07
PT3175706T (pt) 2019-02-11
HK1209275A1 (en) 2016-04-01
KR20220032125A (ko) 2022-03-15
PL3175706T3 (pl) 2019-05-31
EP3175706A1 (en) 2017-06-07
US9462794B2 (en) 2016-10-11
IL244187A0 (en) 2016-04-21
JP2021104064A (ja) 2021-07-26
AU2024216527A1 (en) 2024-09-19
US20190124895A1 (en) 2019-05-02
US20210251201A1 (en) 2021-08-19
KR20160056900A (ko) 2016-05-20
RU2671166C2 (ru) 2018-10-29
HRP20231121T1 (hr) 2023-12-22
KR102370419B1 (ko) 2022-03-04
SG11201601184UA (en) 2016-03-30
US9127292B2 (en) 2015-09-08
JP6453893B2 (ja) 2019-01-16
IL297607A (en) 2022-12-01
AU2020286187A1 (en) 2021-01-07
TR201901782T4 (tr) 2019-03-21
SI3434101T1 (sl) 2023-11-30
WO2015042557A4 (en) 2015-06-18
IL297607B2 (en) 2024-01-01
MX368931B (es) 2019-10-22
MX2016003636A (es) 2016-07-21
SG10201801326PA (en) 2018-03-28
IL278679B2 (en) 2023-04-01
ZA201601138B (en) 2020-06-24
EP2922394A1 (en) 2015-09-30
IL278679A (en) 2022-12-01
JP2019047818A (ja) 2019-03-28
US9901083B2 (en) 2018-02-27
JP7149370B2 (ja) 2022-10-06
WO2015042557A1 (en) 2015-03-26
ES2959333T3 (es) 2024-02-23
EP4269430A2 (en) 2023-11-01
RU2016110462A (ru) 2017-10-30
EP3434101B1 (en) 2023-08-16
CN105592695B (zh) 2018-04-10
US20150089679A1 (en) 2015-03-26
CN105592695A (zh) 2016-05-18
US10426146B2 (en) 2019-10-01
PH12016500342A1 (en) 2016-05-02
US20200187468A1 (en) 2020-06-18
US11019810B2 (en) 2021-06-01
PT2922394T (pt) 2017-05-22
CA2925564A1 (en) 2015-03-26
AU2014321187B2 (en) 2020-09-17
HRP20190227T1 (hr) 2019-06-14
KR102407354B1 (ko) 2022-06-10
US9700027B2 (en) 2017-07-11
SG10201902547SA (en) 2019-04-29
US20170265442A1 (en) 2017-09-21
ES2710282T3 (es) 2019-04-24
CN108441497A (zh) 2018-08-24
RS64573B1 (sr) 2023-10-31
RS58365B1 (sr) 2019-03-29
PL3434101T3 (pl) 2024-02-19
FI3434101T3 (fi) 2023-10-02
DK3175706T3 (da) 2019-03-04
CA2925564C (en) 2023-03-21
JP6875573B2 (ja) 2021-05-26
EP4269430A3 (en) 2024-01-10
LT3175706T (lt) 2019-02-25
AU2020286187B2 (en) 2024-06-13
JP6665269B2 (ja) 2020-03-13
US20160374321A1 (en) 2016-12-29
EP2922394B1 (en) 2017-02-22
RU2016110462A3 (da) 2018-03-30
PT3434101T (pt) 2023-09-19
JP2020114209A (ja) 2020-07-30
US20150089678A1 (en) 2015-03-26
IL262958A (en) 2018-12-31
LT3434101T (lt) 2023-09-25
DK2922394T3 (da) 2017-05-15

Similar Documents

Publication Publication Date Title
DK3434101T5 (da) Ikke-menneskelige dyr, der har et humaniseret signalregulerende proteingen
SMT201700024B (it) Animali con il-15 umanizzata
DK3223605T3 (da) Ikke-humane dyr, der eksprimerer humaniseret cd3-kompleks
DK3376857T3 (da) Ikke-humane dyr, der har et humaniseret lymfocyt-aktiveringsgen 3
DK3482629T3 (da) Genmodificerede ikke-humane dyr, der eksprimerer humant epo
DK3466255T3 (da) Ikke-humane dyr med en humaniseret klynge af differentiering af 47-gen
DK3071595T3 (da) Humaniseret anti-kallikrein-2-antistof
BR302014001381S1 (pt) Configuração aplicada em bolsa.
BR302013006798S1 (pt) Configuração aplicada em halter.
DK3087700T3 (da) Dataindfangning
DK3129400T3 (da) Ikke-humane dyr med humaniserede Fc-gamma-receptorer
IL243581A0 (en) Non-human animals with lincrna deficiency
CL2015003007A1 (es) Carboxamidas fungicidas.
DK3039033T3 (da) Bindende polypeptider, der har et muteret skelet
MA43962A (fr) Animaux non humains possédant un gène angptl8 modifié
BR112016006859A2 (pt) variantes de acetil-coa carboxilase melhoradas.
FI10205U1 (fi) Pölkkyyn kiinnitettävä klapisieppari
UA25336S (uk) Коток польовий
TH1601002070A (th) สัตว์ที่ได้รับการฮิวมาไนซ์ด้วย il-15
TH1601001594A (th) สัตว์ที่ไม่ใช่มนุษย์ซึ่งมียีนโปรตีนควบคุมสัญญาณที่ได้รับการฮิวมาไนซ์
FR3011726B3 (fr) Un grille-pain
DK3071509T3 (da) En donkraft
ES1091810Y (es) Sifon autolimpiable
FI10300U1 (fi) Uistin
TH148359B (th) ไพรโรลิดีน-2-คาร์บอกซาไมด์ที่ถูกแทนที่