DE14176593T1 - ADAM6 Mäuse - Google Patents
ADAM6 Mäuse Download PDFInfo
- Publication number
- DE14176593T1 DE14176593T1 DE14176593.3T DE14176593T DE14176593T1 DE 14176593 T1 DE14176593 T1 DE 14176593T1 DE 14176593 T DE14176593 T DE 14176593T DE 14176593 T1 DE14176593 T1 DE 14176593T1
- Authority
- DE
- Germany
- Prior art keywords
- rodent
- cell
- sequence
- antibody
- antigen
- 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.)
- Pending
Links
- 241000699670 Mus sp. Species 0.000 title 1
- 241000283984 Rodentia Species 0.000 claims abstract 22
- 108700028369 Alleles Proteins 0.000 claims abstract 12
- 108060003951 Immunoglobulin Proteins 0.000 claims abstract 12
- 210000003719 b-lymphocyte Anatomy 0.000 claims abstract 12
- 102000018358 immunoglobulin Human genes 0.000 claims abstract 12
- 210000000349 chromosome Anatomy 0.000 claims abstract 4
- 239000000427 antigen Substances 0.000 claims 12
- 108091007433 antigens Proteins 0.000 claims 12
- 102000036639 antigens Human genes 0.000 claims 12
- 210000004027 cell Anatomy 0.000 claims 9
- 238000000034 method Methods 0.000 claims 6
- 150000007523 nucleic acids Chemical group 0.000 claims 6
- 108090000623 proteins and genes Proteins 0.000 claims 6
- 230000003053 immunization Effects 0.000 claims 4
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 3
- 238000012258 culturing Methods 0.000 claims 3
- 108020004707 nucleic acids Proteins 0.000 claims 3
- 102000039446 nucleic acids Human genes 0.000 claims 3
- 102000004169 proteins and genes Human genes 0.000 claims 3
- 108020004414 DNA Proteins 0.000 claims 2
- 210000004408 hybridoma Anatomy 0.000 claims 2
- 210000004962 mammalian cell Anatomy 0.000 claims 2
- 108010009817 Immunoglobulin Constant Regions Proteins 0.000 claims 1
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 claims 1
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 claims 1
- 108700019146 Transgenes Proteins 0.000 claims 1
- 239000012634 fragment Substances 0.000 claims 1
- 102000053391 human F Human genes 0.000 claims 1
- 108700031895 human F Proteins 0.000 claims 1
- 210000004988 splenocyte Anatomy 0.000 claims 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B60—VEHICLES IN GENERAL
- B60H—ARRANGEMENTS OF HEATING, COOLING, VENTILATING OR OTHER AIR-TREATING DEVICES SPECIALLY ADAPTED FOR PASSENGER OR GOODS SPACES OF VEHICLES
- B60H1/00—Heating, cooling or ventilating [HVAC] devices
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
- A01K67/027—New breeds of vertebrates
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
- A01K67/027—New breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
- A01K67/0278—Humanized animals, e.g. knockin
-
- 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
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New breeds of animals
- A01K67/027—New breeds of vertebrates
- A01K67/0275—Genetically modified vertebrates, e.g. transgenic
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B60—VEHICLES IN GENERAL
- B60H—ARRANGEMENTS OF HEATING, COOLING, VENTILATING OR OTHER AIR-TREATING DEVICES SPECIALLY ADAPTED FOR PASSENGER OR GOODS SPACES OF VEHICLES
- B60H1/00—Heating, cooling or ventilating [HVAC] devices
- B60H1/22—Heating, cooling or ventilating [HVAC] devices the heat being derived otherwise than from the propulsion plant
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B60—VEHICLES IN GENERAL
- B60H—ARRANGEMENTS OF HEATING, COOLING, VENTILATING OR OTHER AIR-TREATING DEVICES SPECIALLY ADAPTED FOR PASSENGER OR GOODS SPACES OF VEHICLES
- B60H1/00—Heating, cooling or ventilating [HVAC] devices
- B60H1/32—Cooling devices
- B60H1/3204—Cooling devices using compression
- B60H1/3228—Cooling devices using compression characterised by refrigerant circuit configurations
- B60H1/32281—Cooling devices using compression characterised by refrigerant circuit configurations comprising a single secondary circuit, e.g. at evaporator or condenser side
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B60—VEHICLES IN GENERAL
- B60H—ARRANGEMENTS OF HEATING, COOLING, VENTILATING OR OTHER AIR-TREATING DEVICES SPECIALLY ADAPTED FOR PASSENGER OR GOODS SPACES OF VEHICLES
- B60H1/00—Heating, cooling or ventilating [HVAC] devices
- B60H1/32—Cooling devices
- B60H1/3204—Cooling devices using compression
- B60H1/323—Cooling devices using compression characterised by comprising auxiliary or multiple systems, e.g. plurality of evaporators, or by involving auxiliary cooling devices
-
- 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
-
- 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
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- 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
-
- 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
- C07K16/2866—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against receptors for cytokines, lymphokines, interferons
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
- C07K16/462—Igs containing a variable region (Fv) from one specie and a constant region (Fc) from another
-
- 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
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
- C12N9/14—Hydrolases (3)
- C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
- C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
- C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
- C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
- C12N9/6489—Metalloendopeptidases (3.4.24)
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2217/00—Genetically modified animals
- A01K2217/15—Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; CARE OF BIRDS, FISHES, INSECTS; 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; CARE OF BIRDS, FISHES, INSECTS; 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
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B60—VEHICLES IN GENERAL
- B60H—ARRANGEMENTS OF HEATING, COOLING, VENTILATING OR OTHER AIR-TREATING DEVICES SPECIALLY ADAPTED FOR PASSENGER OR GOODS SPACES OF VEHICLES
- B60H1/00—Heating, cooling or ventilating [HVAC] devices
- B60H1/00642—Control systems or circuits; Control members or indication devices for heating, cooling or ventilating devices
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B60—VEHICLES IN GENERAL
- B60H—ARRANGEMENTS OF HEATING, COOLING, VENTILATING OR OTHER AIR-TREATING DEVICES SPECIALLY ADAPTED FOR PASSENGER OR GOODS SPACES OF VEHICLES
- B60H1/00—Heating, cooling or ventilating [HVAC] devices
- B60H1/00007—Combined heating, ventilating, or cooling devices
- B60H1/00021—Air flow details of HVAC devices
- B60H2001/00185—Distribution of conditionned air
- B60H2001/00192—Distribution of conditionned air to left and right part of passenger compartment
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B60—VEHICLES IN GENERAL
- B60H—ARRANGEMENTS OF HEATING, COOLING, VENTILATING OR OTHER AIR-TREATING DEVICES SPECIALLY ADAPTED FOR PASSENGER OR GOODS SPACES OF VEHICLES
- B60H1/00—Heating, cooling or ventilating [HVAC] devices
- B60H1/00007—Combined heating, ventilating, or cooling devices
- B60H1/00021—Air flow details of HVAC devices
- B60H2001/00185—Distribution of conditionned air
- B60H2001/002—Distribution of conditionned air to front and rear part of passenger compartment
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—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
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/20—Pseudochromosomes, minichrosomosomes
- C12N2800/204—Pseudochromosomes, minichrosomosomes of bacterial origin, e.g. BAC
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2800/00—Nucleic acids vectors
- C12N2800/30—Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT
Abstract
Ein Nagetier umfassend eine B-Zelle, die eine umgelagerte Immunglobulinsequenz umfasst, die mit einer Sequenz der konstanten Region einer Nagetier-Schwere-Kette funktionsfähig verknüpft ist, die umgelagerte Immunglobulinsequenz umfassend eine V-, D- und/oder J-Sequenz einer humanen schweren Kette, die B-Zelle umfassend in ihrem Genom eine integrierte Adam6-Sequenz oder Ortholog oder Homolog davon, wobei die integrierte Adam6-Sequenz (a) in einem ersten Allel aber nicht in einem zweiten Allel vorhanden ist und auf demselben Chromosom ist wie die umgelagerte Immunglobulinsequenz; oder (b) in einem ersten Allel und einem zweiten Allel vorhanden ist; oder (c) in einem ersten Allel aber nicht in einem zweiten Allel vorhanden ist und auf einem unterschiedlichen Chromosom ist als die umgelagerte Immunglobulinsequenz.
Claims (16)
- Ein Nagetier umfassend eine B-Zelle, die eine umgelagerte Immunglobulinsequenz umfasst, die mit einer Sequenz der konstanten Region einer Nagetier-Schwere-Kette funktionsfähig verknüpft ist, die umgelagerte Immunglobulinsequenz umfassend eine V-, D- und/oder J-Sequenz einer humanen schweren Kette, die B-Zelle umfassend in ihrem Genom eine integrierte Adam6-Sequenz oder Ortholog oder Homolog davon, wobei die integrierte Adam6-Sequenz (a) in einem ersten Allel aber nicht in einem zweiten Allel vorhanden ist und auf demselben Chromosom ist wie die umgelagerte Immunglobulinsequenz; oder (b) in einem ersten Allel und einem zweiten Allel vorhanden ist; oder (c) in einem ersten Allel aber nicht in einem zweiten Allel vorhanden ist und auf einem unterschiedlichen Chromosom ist als die umgelagerte Immunglobulinsequenz.
- Das Nagetier von Anspruch 1, wobei die Adam6-Sequenz auf einem Transgen ist, das von einem heterologen Promoter getrieben wird, wobei vorzugsweise der heterologe Promoter ein nicht-Immunglobulin-Promoter ist.
- Das Nagetier von Anspruch 1 oder 2, wobei die Sequenz der konstanten Region einer Nagetier-Schwere-Kette eine Sequenz einer Nagetier-Schwere-Kette umfasst, ausgewählt aus der Gruppe, bestehend aus einer CH1, einem Gelenk, einer CH2, einer CH3 und einer Kombination davon.
- Das Nagetier von einem der Ansprüche 1–3, wobei eine Mehrheit der B-Zellen des Nagetiers jene integrierte Adam6-Sequenz oder Ortholog oder Homolog davon umfasst.
- Das Nagetier von einem der Ansprüche 1–4, wobei mindestens 90% der B-Zellen des Nagetiers in ihrem Genom jene integrierte Adam6-Sequenz oder Ortholog oder Homolog davon umfassen.
- Eine Nagetier-B-Zelle umfassend eine umgelagerte nicht-endogene Immunglobulin-variable-Gensequenz, die mit einem Nagetier-Immunglobulin-konstante-Region-Gen funktionsfähig verknüpft ist, wobei die B-Zelle eine integrierte Nukleinsäuresequenz umfasst, die für ein in einem männlichen Nagetier funktionellen Adam6-Protein oder Ortholog oder Homolog davon kodiert.
- Die B-Zelle von Anspruch 6, wobei jene integrierte Nukleinsäuresequenz auf einem Nukleinsäuremolekül ist, das an die umgelagerte nicht-endogene Immunglobulin-variable-Gensequenz angrenzt.
- Die B-Zelle von Anspruch 6, wobei jene integrierte Nukleinsäuresequenz auf einem Nukleinsäuremolekül ist, das von dem Nukleinsäuremolekül verschieden ist, das die umgelagerte nicht-endogene Immunglobulin-variable-Gensequenz umfasst.
- Eine Hybridomzelle die aus der B-Zelle nach einem der Ansprüche 6–8 erzeugt wird.
- Verwendung eines Nagetiers entsprechend einem der Ansprüche 1–5 zur Herstellung eines chimären Antikörpers, eines vollständig humanen Antikörpers, eines vollständig humanen Fab-Fragments und/oder eines vollständig humanen F(ab)2-Fragments.
- Ein Verfahren zur Herstellung eines Antikörpers, der spezifisch gegen ein Antigen ist, umfassen die Schritte von: a) Immunisieren eines Nagetiers entsprechend einem der Ansprüche 1–5 mit dem Antigen; b) Isolieren mindestens einer Zelle aus dem Nagetier, das den Antikörper herstellt, der spezifisch gegen das Antigen ist; und c) Kultivieren mindestens einer Zelle die den Antikörper aus Schritt b) herstellt und Erhalten jenes Antikörpers, wobei vorzugsweise das Kultivieren in Schritt c) mit mindestens einer Hybridomzelle durchgeführt wird, die von der mindestens einen in Schritt b) erhaltenen Zelle hergestellt wurde.
- Ein Verfahren zur Herstellung eines vollständig humanen Antikörpers, der spezifisch gegen ein Antigen ist, umfassen die Schritte von: a) Immunisieren eines Nagetiers entsprechend einem der Ansprüche 1–5 mit dem Antigen; b) Isolieren mindestens einer Zelle aus dem Nagetier, das den Antikörper herstellt, der spezifisch gegen das Antigen ist; c) Erzeugen mindestens einer Zelle, die den vollständig humanen Antikörper herstellt, der von dem Antikörper aus Schritt b) abgeleitet wurde und spezifisch gegen das Antigen ist; und d) Kultivieren mindestens einer Zelle die den Antikörper aus Schritt c) herstellt und Erhalten jenes Antikörpers.
- Ein Verfahren zur Herstellung eines vollständig humanen Antikörpers, der spezifisch gegen ein Antigen ist, umfassen die Schritte von: a) Expression in einer Säugetierzelle jenes vollständig humanen Antikörpers, für den ein oder mehr variable-Region-Sequenzen abgeleitet wurden durch: i) Immunisieren eines Nagetiers entsprechend einem der Ansprüche 1–5 mit dem Antigen; ii) Isolieren mindestens einer Zelle aus dem Nagetier, das den Antikörper herstellt, der spezifisch gegen das Antigen ist; iii) Bestimmen einer oder mehr variable-Region-Sequenzen des hergestellten Antikörpers; und b) Kultivieren der Säugetierzelle, so dass der vollständig humane Antikörper hergestellt wird; und c) Erhalten jenes vollständig humanen Antikörpers.
- Das Verfahren von einem der Ansprüche 11 und 12, wobei die mindestens eine in Schritt b) erhaltene Zelle ein Splenozyt oder eine B-Zelle ist.
- Das Verfahren nach einem der Ansprüche 11–13, wobei der Antikörper ein monoklonaler Antikörper ist.
- Das Verfahren nach einem der Ansprüche 11–14, wobei Immunisieren mit dem Antigen im Schritt a) mit einem Protein, DNA, einer Kombination von DNA und Protein, oder Zellen, die das Antigen exprimieren, durchgeführt wird.
Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201161446895P | 2011-02-25 | 2011-02-25 | |
US201161446895P | 2011-02-25 | ||
US201161497650P | 2011-06-16 | 2011-06-16 | |
US201161497650P | 2011-06-16 | ||
US201261595200P | 2012-02-06 | 2012-02-06 | |
US201261595200P | 2012-02-06 | ||
EP14176593.3A EP2813573B1 (de) | 2011-02-25 | 2012-02-24 | Adam6 mäuse |
Publications (1)
Publication Number | Publication Date |
---|---|
DE14176593T1 true DE14176593T1 (de) | 2015-03-05 |
Family
ID=45998616
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE12716101T Pending DE12716101T1 (de) | 2011-02-25 | 2012-02-24 | Adam6-mäuse |
DE14154967.5T Pending DE14154967T1 (de) | 2011-02-25 | 2012-02-24 | ADAM6 Mäuse |
DE12192727T Pending DE12192727T1 (de) | 2011-02-25 | 2012-02-24 | ADAM6 Mäuse |
DE14154918.8T Pending DE14154918T1 (de) | 2011-02-25 | 2012-02-24 | ADAM6 Mäuse |
DE14176593.3T Pending DE14176593T1 (de) | 2011-02-25 | 2012-02-24 | ADAM6 Mäuse |
Family Applications Before (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE12716101T Pending DE12716101T1 (de) | 2011-02-25 | 2012-02-24 | Adam6-mäuse |
DE14154967.5T Pending DE14154967T1 (de) | 2011-02-25 | 2012-02-24 | ADAM6 Mäuse |
DE12192727T Pending DE12192727T1 (de) | 2011-02-25 | 2012-02-24 | ADAM6 Mäuse |
DE14154918.8T Pending DE14154918T1 (de) | 2011-02-25 | 2012-02-24 | ADAM6 Mäuse |
Country Status (32)
Country | Link |
---|---|
US (11) | US8642835B2 (de) |
EP (7) | EP2738259B1 (de) |
JP (7) | JP2014507137A (de) |
KR (1) | KR101387377B1 (de) |
CN (2) | CN103429746B (de) |
AU (5) | AU2012243291B2 (de) |
BR (1) | BR112013021771B1 (de) |
CA (1) | CA2820824A1 (de) |
CY (5) | CY1116301T1 (de) |
DE (5) | DE12716101T1 (de) |
DK (6) | DK2550363T3 (de) |
ES (6) | ES2805364T3 (de) |
FI (3) | FI2738258T4 (de) |
HK (2) | HK1201292A1 (de) |
HR (5) | HRP20230526T1 (de) |
HU (5) | HUE024534T2 (de) |
IL (4) | IL226727A (de) |
IN (1) | IN2013CN07629A (de) |
LT (4) | LT2738258T (de) |
ME (3) | ME03732B (de) |
MX (2) | MX343009B (de) |
MY (1) | MY172713A (de) |
NZ (2) | NZ731926A (de) |
PL (5) | PL2550363T3 (de) |
PT (5) | PT2550363E (de) |
RS (5) | RS59929B1 (de) |
RU (2) | RU2722373C2 (de) |
SG (4) | SG10201913155QA (de) |
SI (5) | SI2550363T1 (de) |
SM (1) | SMT201500061B (de) |
WO (1) | WO2012141798A1 (de) |
ZA (1) | ZA201305998B (de) |
Families Citing this family (74)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
US20050144655A1 (en) | 2000-10-31 | 2005-06-30 | Economides Aris N. | Methods of modifying eukaryotic cells |
JP4836451B2 (ja) | 2002-07-18 | 2011-12-14 | メルス ベー ヴェー | 抗体混合物の組換え生産 |
USRE47770E1 (en) | 2002-07-18 | 2019-12-17 | Merus N.V. | Recombinant production of mixtures of antibodies |
US20100069614A1 (en) | 2008-06-27 | 2010-03-18 | Merus B.V. | Antibody producing non-human mammals |
CA2527694C (en) | 2003-05-30 | 2015-07-14 | Hendricus Renerus Jacobus Mattheus Hoogenboom | Fab library for the preparation of anti vegf and anti rabies virus fabs |
JP2008512987A (ja) | 2004-07-22 | 2008-05-01 | エラスムス・ユニヴァーシティ・メディカル・センター・ロッテルダム | 結合分子 |
GB0905023D0 (en) | 2009-03-24 | 2009-05-06 | Univ Erasmus Medical Ct | Binding molecules |
US9445581B2 (en) | 2012-03-28 | 2016-09-20 | Kymab Limited | Animal models and therapeutic molecules |
US20120204278A1 (en) | 2009-07-08 | 2012-08-09 | Kymab Limited | Animal models and therapeutic molecules |
BR112012000536A2 (pt) | 2009-07-08 | 2020-08-11 | Kymab Limited | métodos para produção de anticorpo ou cadeia leve ou pesada de anticorpo específico para um antígeno desejado, para produção de anticorpo ou cadeia de anticorpo e seu uso, composição farmacêutica e derivado de anticorpo quimérico |
US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
US20130045492A1 (en) | 2010-02-08 | 2013-02-21 | Regeneron Pharmaceuticals, Inc. | Methods For Making Fully Human Bispecific Antibodies Using A Common Light Chain |
ES2547142T5 (es) | 2010-02-08 | 2021-12-09 | Regeneron Pharma | Cadena ligera común de ratón |
NZ606824A (en) | 2010-08-02 | 2015-05-29 | Regeneron Pharma | Mice that make binding proteins comprising vl domains |
HUE024534T2 (hu) | 2011-02-25 | 2016-01-28 | Regeneron Pharma | ADAM6 egerek |
US10040826B2 (en) | 2011-07-05 | 2018-08-07 | Duke University | Human immunodeficiency virus type 1 (HIV-1) N-terminal deleted GP120 immunogens |
IL297371A (en) * | 2011-08-05 | 2022-12-01 | Regeneron Pharma | Humanized mice possess a universal light chain |
JP2014531452A (ja) | 2011-09-19 | 2014-11-27 | カイマブ・リミテッド | 動物、レパートリーおよび方法 |
AU2012311286B2 (en) | 2011-09-19 | 2018-07-26 | Kymab Limited | Antibodies, variable domains and chains tailored for human use |
EP2761008A1 (de) | 2011-09-26 | 2014-08-06 | Kymab Limited | Chimäre surrogatleichtketten (slc) mit humanem vpreb |
CA2850745C (en) | 2011-10-03 | 2022-12-13 | Duke University | Vaccine |
HUE057680T2 (hu) * | 2011-10-17 | 2022-06-28 | Regeneron Pharma | Korlátozott immunglobulin-nehézlánccal rendelkezõ egerek |
GB201122047D0 (en) | 2011-12-21 | 2012-02-01 | Kymab Ltd | Transgenic animals |
US9253965B2 (en) | 2012-03-28 | 2016-02-09 | Kymab Limited | Animal models and therapeutic molecules |
SI2793567T1 (sl) | 2011-12-20 | 2019-05-31 | Regeneron Pharmaceuticals, Inc. | Humanizirane lahkoverižne miši |
EP3912465A1 (de) * | 2012-02-01 | 2021-11-24 | Regeneron Pharmaceuticals, Inc. | Humanisierte nager, die schwere ketten mit vl-domänen exprimieren |
US20140013456A1 (en) | 2012-03-16 | 2014-01-09 | Regeneron Pharmaceuticals, Inc. | Histidine Engineered Light Chain Antibodies and Genetically Modified Non-Human Animals for Generating the Same |
NZ629077A (en) | 2012-03-16 | 2015-12-24 | Regeneron Pharma | Non-human animals expressing ph-sensitive immunoglobulin sequences |
KR20140134672A (ko) | 2012-03-16 | 2014-11-24 | 리제너론 파마슈티칼스 인코포레이티드 | pH-의존성 결합 특성을 나타내는 항원-결합 단백질을 생성하는 마우스 |
HUE037659T2 (hu) | 2012-03-16 | 2018-09-28 | Regeneron Pharma | Hisztidinmódosított könnyûlánc antitestek és genetikailag módosított rágcsálók ennek az elõállítására |
GB2502127A (en) | 2012-05-17 | 2013-11-20 | Kymab Ltd | Multivalent antibodies and in vivo methods for their production |
US10251377B2 (en) | 2012-03-28 | 2019-04-09 | Kymab Limited | Transgenic non-human vertebrate for the expression of class-switched, fully human, antibodies |
JP6272299B2 (ja) | 2012-04-20 | 2018-01-31 | メルス ナムローゼ フェンノートシャップ | Ig様分子を生産する方法、Ig様分子の混合物、組み換え宿主細胞、医薬組成物、宿主細胞を作成する方法、および培養物 |
EP3912464A1 (de) | 2012-06-12 | 2021-11-24 | Regeneron Pharmaceuticals, Inc. | Humanisierte nichtmenschliche tiere mit eingeschränkten schwerkettigen immunglobulin-loci |
EP2953452A1 (de) | 2013-02-06 | 2015-12-16 | Regeneron Pharmaceuticals, Inc. | Auf b-zelllinien basierendes immunogen-design mit humanisierten tieren |
PT2840892T (pt) * | 2013-02-20 | 2018-07-20 | Regeneron Pharma | Animais não humanos com sequências da cadeia pesada da imunoglobulina modificada |
EP2967012B1 (de) * | 2013-03-14 | 2020-09-16 | Erasmus University Medical Center Rotterdam | Transgenes nicht-menschliches säugetier für die produktion von antikörpern |
WO2014141192A1 (en) * | 2013-03-15 | 2014-09-18 | Erasmus University Medical Center | Generation of heavy chain-only antibodies |
US9788534B2 (en) | 2013-03-18 | 2017-10-17 | Kymab Limited | Animal models and therapeutic molecules |
US9783618B2 (en) | 2013-05-01 | 2017-10-10 | Kymab Limited | Manipulation of immunoglobulin gene diversity and multi-antibody therapeutics |
US11707056B2 (en) | 2013-05-02 | 2023-07-25 | Kymab Limited | Animals, repertoires and methods |
US9783593B2 (en) | 2013-05-02 | 2017-10-10 | Kymab Limited | Antibodies, variable domains and chains tailored for human use |
CN105683365A (zh) | 2013-10-01 | 2016-06-15 | 科马布有限公司 | 动物模型及治疗分子 |
JP6267986B2 (ja) * | 2014-02-13 | 2018-01-24 | 株式会社特殊免疫研究所 | ヒトの特定分子と結合する分子標的物質のinvivo評価法 |
CA2941514A1 (en) | 2014-03-21 | 2015-09-24 | Regeneron Pharmaceuticals, Inc. | Vl antigen binding proteins exhibiting distinct binding characteristics |
JP6636498B2 (ja) | 2014-03-21 | 2020-01-29 | 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Regeneron Pharmaceuticals, Inc. | 単一ドメイン結合タンパク質を作る非ヒト動物 |
AU2015317370A1 (en) | 2014-09-19 | 2017-03-23 | Regeneron Pharmaceuticals, Inc. | Chimeric antigen receptors |
WO2016149678A1 (en) | 2015-03-19 | 2016-09-22 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
KR20230006929A (ko) | 2016-01-13 | 2023-01-11 | 리제너론 파마슈티칼스 인코포레이티드 | 조작된 중쇄 다양성 영역을 갖는 설치류 |
MA44242A (fr) | 2016-02-16 | 2018-12-26 | Regeneron Pharma | Animaux non humains ayant un gène de kynuréninase mutant |
AU2017268458B2 (en) * | 2016-05-20 | 2022-07-21 | Regeneron Pharmaceuticals, Inc. | Methods for breaking immunological tolerance using multiple guide RNAS |
KR102598120B1 (ko) | 2016-06-03 | 2023-11-07 | 리제너론 파마슈티칼스 인코포레이티드 | 외인성 말단 데옥시뉴클레오타이드 전달효소를 발현하는 비인간 동물 |
WO2017214089A1 (en) | 2016-06-06 | 2017-12-14 | Regeneron Pharmaceuticals, Inc. | Non-human animals expressing antibodies with human lambda light chains |
CA3038720A1 (en) | 2016-11-04 | 2018-07-12 | Regeneron Pharmaceuticals, Inc. | Non-human animals having an engineered immunoglobulin lambda light chain locus |
US11122042B1 (en) | 2017-05-12 | 2021-09-14 | F5 Networks, Inc. | Methods for dynamically managing user access control and devices thereof |
KR20200015932A (ko) | 2017-06-07 | 2020-02-13 | 리제너론 파마슈티칼스 인코포레이티드 | 효소 내재화를 위한 조성물 및 방법 |
PT3720279T (pt) | 2017-12-05 | 2022-10-06 | Regeneron Pharma | Ratinhos tendo uma cadeia leve lambda de imunoglobulina manipulada e seus usos |
CN116874591A (zh) | 2018-03-24 | 2023-10-13 | 瑞泽恩制药公司 | 用于产生针对肽-mhc复合物的治疗性抗体的经过基因修饰的非人动物、其制造方法和用途 |
SG11202008620VA (en) | 2018-03-26 | 2020-10-29 | Regeneron Pharma | Humanized rodents for testing therapeutic agents |
BR112020023145A2 (pt) | 2018-05-17 | 2021-02-02 | Regeneron Pharmaceuticals, Inc. | anticorpo anti-cd63 ou fragmento de ligação ao antígeno do mesmo, molécula de ligação ao antígeno biespecífica, proteína terapêutica de múltiplos domínios, polinucleotídeo composição farmacêutica, e, composto |
US20210230629A1 (en) * | 2018-06-13 | 2021-07-29 | Crystal Bioscience Inc. | Camelization of a human variable domain by gene conversion |
EP4023059A1 (de) | 2018-06-14 | 2022-07-06 | Regeneron Pharmaceuticals, Inc. | Nicht-menschliche tiere mit der fähigkeit zur dh-dh-neuanordnung in den schwerkettencodierungssequenzen von immunoglobulinen |
CA3125380A1 (en) | 2019-02-18 | 2020-08-27 | Biocytogen Pharmaceuticals (Beijing) Co., Ltd. | Genetically modified non-human animals with humanized immunoglobulin locus |
KR20210129083A (ko) | 2019-02-22 | 2021-10-27 | 리제너론 파마슈티칼스 인코포레이티드 | 유전적으로 변형된 나트륨 채널을 갖는 설치류 및 이의 사용 방법 |
JP2022535418A (ja) | 2019-06-05 | 2022-08-08 | 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 | カッパ遺伝子座から発現される限られたラムダ軽鎖レパートリーを有する非ヒト動物及びその使用 |
EP3785536B1 (de) * | 2019-08-28 | 2022-01-26 | Trianni, Inc. | Adam6-knockin-mäuse |
AU2020395122A1 (en) | 2019-12-02 | 2022-06-09 | Regeneron Pharmaceuticals, Inc. | Peptide-MHC II protein constructs and uses thereof |
IL301137A (en) | 2020-09-11 | 2023-05-01 | Regeneron Pharma | Identification and production of antigen-specific antibodies |
US20240065239A1 (en) | 2020-12-16 | 2024-02-29 | Regeneron Pharmaceuticals, Inc. | Mice expressing humanized fc alpha receptors |
AU2021410655A1 (en) | 2020-12-23 | 2023-06-29 | Regeneron Pharmaceuticals, Inc. | Nucleic acids encoding anchor modified antibodies and uses thereof |
CN116635413A (zh) | 2020-12-23 | 2023-08-22 | 再生元制药公司 | 用于获得结合跨膜蛋白的抗体的方法和生产所述抗体的细胞 |
CA3212049A1 (en) | 2021-04-20 | 2022-10-27 | Susan D. Croll | Human antibodies to artemin and methods of use thereof |
WO2024015816A1 (en) | 2022-07-12 | 2024-01-18 | Regeneron Pharmaceuticals, Inc. | Antibodies to ciliary neurotrophic factor receptor (cntfr) and methods of use thereof |
Family Cites Families (47)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB8823869D0 (en) | 1988-10-12 | 1988-11-16 | Medical Res Council | Production of antibodies |
WO1991000906A1 (en) | 1989-07-12 | 1991-01-24 | Genetics Institute, Inc. | Chimeric and transgenic animals capable of producing human antibodies |
US6657103B1 (en) | 1990-01-12 | 2003-12-02 | Abgenix, Inc. | Human antibodies derived from immunized xenomice |
US6673986B1 (en) | 1990-01-12 | 2004-01-06 | Abgenix, Inc. | Generation of xenogeneic antibodies |
US7041871B1 (en) | 1995-10-10 | 2006-05-09 | Genpharm International, Inc. | Transgenic non-human animals capable of producing heterologous antibodies |
KR100371784B1 (ko) * | 1992-12-01 | 2003-07-22 | 프로테인 디자인랩스, 인코포레이티드 | L-셀렉틴과반응성인인체화된항체 |
EP2314625B1 (de) * | 1996-12-03 | 2014-05-07 | Amgen Fremont Inc. | Transgene Säugetiere, die menschliche Ig-loci einschliesslich mehrere VH und Vkappa Regionen enthalten, und davon erhaltene Antikörper |
CN1203922A (zh) * | 1997-03-21 | 1999-01-06 | 三共株式会社 | 人源化抗人fas抗体 |
US20020062010A1 (en) | 1997-05-02 | 2002-05-23 | Genentech, Inc. | Method for making multispecific antibodies having heteromultimeric and common components |
RU10506U1 (ru) | 1999-04-08 | 1999-08-16 | Кривулин Виталий Николаевич | Ручной культиватор |
WO2000073323A2 (en) * | 1999-05-27 | 2000-12-07 | Human Genome Sciences, Inc. | Adam polynucleotides and polypeptides |
GB0001448D0 (en) * | 2000-01-21 | 2000-03-08 | Novartis Ag | Organic compounds |
US7105348B2 (en) | 2000-10-31 | 2006-09-12 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
US6596541B2 (en) | 2000-10-31 | 2003-07-22 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
US6586251B2 (en) | 2000-10-31 | 2003-07-01 | Regeneron Pharmaceuticals, Inc. | Methods of modifying eukaryotic cells |
PE20020574A1 (es) | 2000-12-06 | 2002-07-02 | Wyeth Corp | Anticuerpos humanizados que reconocen el peptido amiloideo beta |
US7034134B2 (en) | 2001-04-26 | 2006-04-25 | Bristol-Myers Squibb Company | Polynucleotide encoding a novel metalloprotease highly expressed in the testis, MMP-29 |
CN100448992C (zh) * | 2001-05-11 | 2009-01-07 | 麒麟医药株式会社 | 含人抗体λ轻链基因的人类人工染色体 |
US7473557B2 (en) | 2001-06-06 | 2009-01-06 | Regeneron Pharmaceuticals, Inc. | Method for targeting transcriptionally active loci |
US20060199204A1 (en) | 2001-10-05 | 2006-09-07 | U.S. Epa | Genetic testing for male factor infertility |
WO2003031656A1 (en) | 2001-10-05 | 2003-04-17 | United States Environmental Protection Agency | Genetic testing for male factor infertility |
JP4099646B2 (ja) | 2002-06-04 | 2008-06-11 | 株式会社安川電機 | ボイスコイルモータ |
JP4836451B2 (ja) | 2002-07-18 | 2011-12-14 | メルス ベー ヴェー | 抗体混合物の組換え生産 |
RU2251699C1 (ru) | 2003-09-25 | 2005-05-10 | Киселев Всеволод Иванович | Способ ранней и доклинической диагностики цервикального рака |
SI1802193T1 (sl) | 2004-10-19 | 2014-08-29 | Regeneron Pharmaceuticals, Inc. | Postopek za generiranje miši, homozigotne za genetsko modifikacijo |
DE602005011421D1 (de) | 2005-06-30 | 2009-01-15 | Borealis Tech Oy | Überzug-Schicht für Energie- oder Kommunikationskabel |
AU2007235496B2 (en) | 2006-03-31 | 2013-11-21 | E. R. Squibb & Sons, L.L.C. | Transgenic animals expressing chimeric antibodies for use in preparing human antibodies |
CN102585002A (zh) | 2006-06-02 | 2012-07-18 | 瑞泽恩制药公司 | 人il-6受体的高亲和力抗体 |
WO2009097006A2 (en) | 2007-08-10 | 2009-08-06 | Medarex, Inc. | Hco32 and hco27 and related examples |
US7659842B2 (en) | 2007-10-24 | 2010-02-09 | Infineon Technologies Ag | Quantization error reduction in PWM full-MASH converters |
NZ592308A (en) | 2008-09-30 | 2012-11-30 | Ablexis Llc | Non-human mammals for the production of chimeric antibodies |
CN112680475A (zh) * | 2008-12-18 | 2021-04-20 | 伊拉兹马斯大学鹿特丹医学中心 | 表达人源化抗体的非人转基因动物及其用途 |
GB0905023D0 (en) | 2009-03-24 | 2009-05-06 | Univ Erasmus Medical Ct | Binding molecules |
JP5399140B2 (ja) * | 2009-06-18 | 2014-01-29 | 株式会社タイトー | モールス信号通信システム |
WO2011158009A1 (en) * | 2010-06-17 | 2011-12-22 | Kymab Limited | Animal models and therapeutic molecules |
US20120204278A1 (en) | 2009-07-08 | 2012-08-09 | Kymab Limited | Animal models and therapeutic molecules |
BR112012000536A2 (pt) * | 2009-07-08 | 2020-08-11 | Kymab Limited | métodos para produção de anticorpo ou cadeia leve ou pesada de anticorpo específico para um antígeno desejado, para produção de anticorpo ou cadeia de anticorpo e seu uso, composição farmacêutica e derivado de anticorpo quimérico |
LT2954779T (lt) * | 2009-12-10 | 2019-05-27 | Regeneron Pharmaceuticals, Inc. | Pelės, gaminančios sunkiosios grandinės antikūnus |
US20120021409A1 (en) | 2010-02-08 | 2012-01-26 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
ES2547142T5 (es) | 2010-02-08 | 2021-12-09 | Regeneron Pharma | Cadena ligera común de ratón |
HUE024534T2 (hu) | 2011-02-25 | 2016-01-28 | Regeneron Pharma | ADAM6 egerek |
IL297371A (en) | 2011-08-05 | 2022-12-01 | Regeneron Pharma | Humanized mice possess a universal light chain |
HUE057680T2 (hu) | 2011-10-17 | 2022-06-28 | Regeneron Pharma | Korlátozott immunglobulin-nehézlánccal rendelkezõ egerek |
GB201118579D0 (en) | 2011-10-27 | 2011-12-07 | Micromass Ltd | Control of ion populations |
US9253965B2 (en) | 2012-03-28 | 2016-02-09 | Kymab Limited | Animal models and therapeutic molecules |
GB201122047D0 (en) * | 2011-12-21 | 2012-02-01 | Kymab Ltd | Transgenic animals |
SI2793567T1 (sl) | 2011-12-20 | 2019-05-31 | Regeneron Pharmaceuticals, Inc. | Humanizirane lahkoverižne miši |
-
2012
- 2012-02-24 HU HUE12716101A patent/HUE024534T2/hu unknown
- 2012-02-24 DE DE12716101T patent/DE12716101T1/de active Pending
- 2012-02-24 PL PL12716101T patent/PL2550363T3/pl unknown
- 2012-02-24 EP EP14154967.5A patent/EP2738259B1/de active Active
- 2012-02-24 LT LTEP14154918.8T patent/LT2738258T/lt unknown
- 2012-02-24 US US13/404,075 patent/US8642835B2/en active Active
- 2012-02-24 DE DE14154967.5T patent/DE14154967T1/de active Pending
- 2012-02-24 ES ES14176593T patent/ES2805364T3/es active Active
- 2012-02-24 RS RS20200177A patent/RS59929B1/sr unknown
- 2012-02-24 WO PCT/US2012/026416 patent/WO2012141798A1/en active Application Filing
- 2012-02-24 LT LTEP14154967.5T patent/LT2738259T/lt unknown
- 2012-02-24 SI SI201230157T patent/SI2550363T1/sl unknown
- 2012-02-24 EP EP14154918.8A patent/EP2738258B2/de active Active
- 2012-02-24 HR HRP20230526TT patent/HRP20230526T1/hr unknown
- 2012-02-24 DK DK12716101.6T patent/DK2550363T3/en active
- 2012-02-24 SI SI201231712T patent/SI2738258T2/sl unknown
- 2012-02-24 DE DE12192727T patent/DE12192727T1/de active Pending
- 2012-02-24 HU HUE22156414A patent/HUE062552T2/hu unknown
- 2012-02-24 RS RS20150163A patent/RS53880B1/en unknown
- 2012-02-24 ME MEP-2020-41A patent/ME03732B/de unknown
- 2012-02-24 DE DE14154918.8T patent/DE14154918T1/de active Pending
- 2012-02-24 CN CN201280010457.XA patent/CN103429746B/zh active Active
- 2012-02-24 HU HUE14154918A patent/HUE046746T2/hu unknown
- 2012-02-24 BR BR112013021771-5A patent/BR112013021771B1/pt active IP Right Grant
- 2012-02-24 DK DK12192727.1T patent/DK2578688T4/da active
- 2012-02-24 PT PT12716101T patent/PT2550363E/pt unknown
- 2012-02-24 RU RU2016109443A patent/RU2722373C2/ru not_active Application Discontinuation
- 2012-02-24 JP JP2013550677A patent/JP2014507137A/ja active Pending
- 2012-02-24 HR HRP20192311TT patent/HRP20192311T4/hr unknown
- 2012-02-24 CA CA2820824A patent/CA2820824A1/en not_active Withdrawn
- 2012-02-24 IN IN7629CHN2013 patent/IN2013CN07629A/en unknown
- 2012-02-24 DK DK14154918.8T patent/DK2738258T4/da active
- 2012-02-24 MY MYPI2013003123A patent/MY172713A/en unknown
- 2012-02-24 PL PL12192727.1T patent/PL2578688T5/pl unknown
- 2012-02-24 SI SI201231739T patent/SI2738259T1/sl unknown
- 2012-02-24 PT PT121927271T patent/PT2578688T/pt unknown
- 2012-02-24 FI FIEP14154918.8T patent/FI2738258T4/fi active
- 2012-02-24 ME MEP-2015-35A patent/ME02106B/me unknown
- 2012-02-24 MX MX2013009649A patent/MX343009B/es active IP Right Grant
- 2012-02-24 EP EP22156414.9A patent/EP4067496B1/de active Active
- 2012-02-24 ES ES14154967T patent/ES2770424T3/es active Active
- 2012-02-24 RS RS20191337A patent/RS59413B2/sr unknown
- 2012-02-24 NZ NZ731926A patent/NZ731926A/en unknown
- 2012-02-24 EP EP12716101.6A patent/EP2550363B1/de active Active
- 2012-02-24 KR KR1020137025191A patent/KR101387377B1/ko active IP Right Grant
- 2012-02-24 PL PL14154967T patent/PL2738259T3/pl unknown
- 2012-02-24 ME MEP2019272 patent/ME03537B/xx unknown
- 2012-02-24 DK DK14154967.5T patent/DK2738259T3/da active
- 2012-02-24 SG SG10201913155QA patent/SG10201913155QA/en unknown
- 2012-02-24 SI SI201232031T patent/SI4067496T1/sl unknown
- 2012-02-24 HR HRP20191895TT patent/HRP20191895T4/hr unknown
- 2012-02-24 DK DK22156414.9T patent/DK4067496T3/da active
- 2012-02-24 SG SG10201913160QA patent/SG10201913160QA/en unknown
- 2012-02-24 ES ES22156414T patent/ES2946169T3/es active Active
- 2012-02-24 PL PL22156414.9T patent/PL4067496T3/pl unknown
- 2012-02-24 FI FIEP12192727.1T patent/FI2578688T4/fi active
- 2012-02-24 DE DE14176593.3T patent/DE14176593T1/de active Pending
- 2012-02-24 SG SG2013064159A patent/SG192933A1/en unknown
- 2012-02-24 PT PT221564149T patent/PT4067496T/pt unknown
- 2012-02-24 ES ES14154918T patent/ES2758974T5/es active Active
- 2012-02-24 PT PT141549188T patent/PT2738258T/pt unknown
- 2012-02-24 SI SI201231675T patent/SI2578688T2/sl unknown
- 2012-02-24 ES ES12192727T patent/ES2748832T5/es active Active
- 2012-02-24 SG SG10201405135RA patent/SG10201405135RA/en unknown
- 2012-02-24 AU AU2012243291A patent/AU2012243291B2/en active Active
- 2012-02-24 EP EP12192727.1A patent/EP2578688B2/de active Active
- 2012-02-24 RS RS20191599A patent/RS59661B2/sr unknown
- 2012-02-24 ES ES12716101.6T patent/ES2532487T3/es active Active
- 2012-02-24 HU HUE14154967A patent/HUE047687T2/hu unknown
- 2012-02-24 PL PL14154918.8T patent/PL2738258T5/pl unknown
- 2012-02-24 HU HUE12192727A patent/HUE046081T2/hu unknown
- 2012-02-24 DK DK14176593.3T patent/DK2813573T1/da unknown
- 2012-02-24 EP EP20170540.7A patent/EP3744850A1/de active Pending
- 2012-02-24 PT PT141549675T patent/PT2738259T/pt unknown
- 2012-02-24 NZ NZ776770A patent/NZ776770A/en unknown
- 2012-02-24 RU RU2013125717/10A patent/RU2582261C2/ru active
- 2012-02-24 LT LT12192727T patent/LT2578688T/lt unknown
- 2012-02-24 LT LTEP22156414.9T patent/LT4067496T/lt unknown
- 2012-02-24 CN CN201610204885.6A patent/CN105861548B/zh active Active
- 2012-02-24 RS RS20230475A patent/RS64280B1/sr unknown
- 2012-02-24 EP EP14176593.3A patent/EP2813573B1/de active Active
-
2013
- 2013-02-08 HK HK15101692.2A patent/HK1201292A1/xx unknown
- 2013-02-08 HK HK13101802.1A patent/HK1174490A1/xx unknown
- 2013-05-09 US US13/890,519 patent/US8697940B2/en active Active
- 2013-06-04 IL IL226727A patent/IL226727A/en active IP Right Grant
- 2013-08-08 ZA ZA2013/05998A patent/ZA201305998B/en unknown
- 2013-08-21 MX MX2020009714A patent/MX2020009714A/es unknown
-
2014
- 2014-02-27 US US14/192,051 patent/US9932408B2/en active Active
- 2014-03-20 JP JP2014057616A patent/JP5866127B2/ja active Active
-
2015
- 2015-01-20 US US14/600,829 patent/US10072095B2/en active Active
- 2015-02-26 JP JP2015036588A patent/JP2015107131A/ja not_active Withdrawn
- 2015-03-03 CY CY20151100221T patent/CY1116301T1/el unknown
- 2015-03-09 HR HRP20150262AT patent/HRP20150262T1/hr unknown
- 2015-03-11 SM SM201500061T patent/SMT201500061B/xx unknown
- 2015-04-09 US US14/682,859 patent/US9944716B2/en active Active
- 2015-10-07 AU AU2015238806A patent/AU2015238806A1/en not_active Abandoned
-
2016
- 2016-04-27 JP JP2016088848A patent/JP2016135143A/ja not_active Withdrawn
-
2017
- 2017-10-26 AU AU2017251802A patent/AU2017251802A1/en not_active Abandoned
-
2018
- 2018-06-04 JP JP2018107070A patent/JP2018143250A/ja not_active Withdrawn
- 2018-08-09 US US16/059,922 patent/US10905109B2/en active Active
- 2018-08-09 US US16/059,884 patent/US10694725B2/en active Active
- 2018-08-09 US US16/059,821 patent/US10905108B2/en active Active
- 2018-08-09 US US16/059,871 patent/US10577430B2/en active Active
- 2018-08-20 IL IL261243A patent/IL261243B/en active IP Right Grant
-
2019
- 2019-07-09 JP JP2019127562A patent/JP2019187446A/ja not_active Withdrawn
- 2019-08-13 IL IL268671A patent/IL268671B/en active IP Right Grant
- 2019-09-19 CY CY20191100988T patent/CY1122205T1/el unknown
- 2019-10-23 CY CY20191101104T patent/CY1122459T1/el unknown
-
2020
- 2020-01-22 CY CY20201100054T patent/CY1122820T1/el unknown
- 2020-02-21 AU AU2020201279A patent/AU2020201279A1/en not_active Abandoned
- 2020-02-21 HR HRP20200294TT patent/HRP20200294T1/hr unknown
- 2020-04-16 IL IL273986A patent/IL273986B/en active IP Right Grant
- 2020-12-21 US US17/129,708 patent/US11950578B2/en active Active
- 2020-12-21 US US17/129,706 patent/US20210105984A1/en active Pending
-
2022
- 2022-02-11 FI FIEP22156414.9T patent/FI4067496T3/fi active
- 2022-02-28 JP JP2022029501A patent/JP2022071051A/ja active Pending
- 2022-07-22 AU AU2022206806A patent/AU2022206806A1/en active Pending
-
2023
- 2023-05-31 CY CY20231100256T patent/CY1126091T1/el unknown
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
DE14176593T1 (de) | ADAM6 Mäuse | |
DE10010741T1 (de) | Verfahren zur Modifikation eukaryotischer Zellen | |
CN104302169B (zh) | 组氨酸工程改造的轻链抗体和用于生成所述抗体的经基因修饰的非人动物 | |
CN104024418B (zh) | 具有受限制的免疫球蛋白重链的小鼠 | |
CN103154255B (zh) | 制造包含vl结构域的结合蛋白的小鼠 | |
CN107105633B (zh) | 表达人源化cd3复合物的非人类动物 | |
CN104582476B (zh) | 使用共同轻链制备完全人双特异性抗体的方法 | |
CN104302171B (zh) | 表达ph敏感性免疫球蛋白序列的非人动物 | |
CN105188357B (zh) | 表达限制的免疫球蛋白轻链库的小鼠 | |
RU2018119366A (ru) | Мыши с гуманизированной легкой цепью | |
US20210355238A1 (en) | Non-human animals that select for light chain variable regions that bind antigen | |
HUE026229T2 (en) | Common light chain mouse | |
CN107090471A (zh) | 共同轻链小鼠 | |
JP2020501516A5 (de) | ||
JP2018500896A5 (de) | ||
JP2015505477A5 (de) | ||
CN109996441A (zh) | 具有经工程化的免疫球蛋白λ轻链基因座的非人类动物 | |
AU2019242586A1 (en) | Humanized rodents for testing therapeutic agents | |
CN111386039B (zh) | 经基因修饰的啮齿动物基因组 | |
CN109280674A (zh) | 一种筛选抗体的非人模式动物的构建方法及其应用 | |
Yu ShanShan et al. | Production of functional chimeric mouse-human antibody to CD20 in the milk of transgenic mice. | |
NZ740900B2 (en) | Mice that make binding proteins comprising vl domains |