ME02106B - Miševi sa adam6 - Google Patents

Miševi sa adam6

Info

Publication number
ME02106B
ME02106B MEP-2015-35A MEP201535A ME02106B ME 02106 B ME02106 B ME 02106B ME P201535 A MEP201535 A ME P201535A ME 02106 B ME02106 B ME 02106B
Authority
ME
Montenegro
Prior art keywords
mouse
heavy chain
modification
endogenous
antibody
Prior art date
Application number
MEP-2015-35A
Other languages
English (en)
Inventor
Lynn Macdonald
Sean Stevens
Andrew J Murphy
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=45998616&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ME02106(B) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Regeneron Pharma filed Critical Regeneron Pharma
Publication of ME02106B publication Critical patent/ME02106B/me

Links

Classifications

    • 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
    • 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 devices
    • 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
    • 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
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    • 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
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    • 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 devices
    • B60H1/22—Heating, cooling or ventilating devices the heat source being other than the propulsion plant
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B60H1/00—Heating, cooling or ventilating devices
    • B60H1/32—Cooling devices
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    • 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
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    • B60H—ARRANGEMENTS OF HEATING, COOLING, VENTILATING OR OTHER AIR-TREATING DEVICES SPECIALLY ADAPTED FOR PASSENGER OR GOODS SPACES OF VEHICLES
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    • 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
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    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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    • C—CHEMISTRY; METALLURGY
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    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • C07K16/28—Immunoglobulins [IG], 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
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    • C07K16/18—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against material from animals or humans
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    • C07K16/2866—Immunoglobulins [IG], 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
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    • C07K16/40—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies against enzymes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07K16/46—Hybrid immunoglobulins
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    • 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
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    • 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
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    • C12N9/14—Hydrolases (3)
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    • 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
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    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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    • A01K2217/072—Animals genetically altered by homologous recombination maintaining or altering function, i.e. knock in
    • A—HUMAN NECESSITIES
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    • 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
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    • A—HUMAN NECESSITIES
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    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B60H2001/002—Distribution of conditionned air to front and rear part of passenger compartment
    • C—CHEMISTRY; METALLURGY
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    • C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
    • C07K2317/21—Immunoglobulins specific features characterized by taxonomic origin from primates, e.g. man
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    • 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
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    • 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
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    • C12N2800/00—Nucleic acids vectors
    • C12N2800/30—Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Environmental Sciences (AREA)
  • General Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Physics & Mathematics (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Husbandry (AREA)
  • Microbiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Mechanical Engineering (AREA)
  • Thermal Sciences (AREA)
  • Plant Pathology (AREA)
  • Toxicology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Coloring Foods And Improving Nutritive Qualities (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Saccharide Compounds (AREA)

Description

SEQUENCE LISTING
 
[0372]
 
<110> Lynn Macdonald
 
Sean Stevens
Andrew J. Murphy
 
<120> ADAM6 Miševi
 
<130> 1360A-WO
 
<140> To be assigned
<141>
<150> 61/595,200
<151> 2012-02-06
<150> 61/497,650
<151> 2011-06-16
<150> 61/446,895
<151> 2011-02-25
<160> 58
<170> FastSEQ for Windows Version 4.0
 
 
 
<210> 1
<211> 754
<212> PRT
<213> Mus musculus
 
 
<400> 1
 
 
 
 
 
 
<210> 2
<211> 756
<212> PRT
<213> Mus musculus
 
 
<400> 2
 
 
 
 
 
<210> 3
<211> 13894
<212> DNA
<213> Umjetni Slijed
 
 
<220>
<223> sintetički
 
 
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<210> 4
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<220>
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<210> 5
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<212> DNA
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<220>
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<220>
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26
 

Claims (14)

1. Miš koji ima genom koji sadrži modifikaciju lokusa teškog lanca imunoglobulina, naznačen time, da modifikacija uklanja endogenu funkciju ADAM6, koja je povezana sa smanjenjem plodnosti kod mužjaka miševa, miš nadalje sadrži sljedove nukleinskih kiselina koji kodiraju mišji protein ADAM6a, ili njegov ortologni ili homologni ili funkcionalni fragment koji je funkcionalan kod mužjaka miša, i mišji ADAM6b protein ili njegov ortologni ili homologni ili funkcionalni fragment koji je funkcionalan kod mužjaka miša.
2. Miš prema zahtjevu 1, naznačen time, da su sljedovi nukleinskih kiselina na endogenom imunoglobulinskom lokusu i pri čemu su sljedovi nukleinskih kiselina integrirani u genom miša, na položaju različitom od položaja endogenog imunoglobulinskog lokusa.
3. Miš prema bilo kojem od zahtjeva 1 do 2, naznačen time, da modifikacija lokusa teškog lanca imunoglobulina podrazumijeva umetanje jednog ili više ljudskih imunoglobulinskih sljedova ili gdje se modifikacija lokusa teškog lanca imunoglobulina sastoji od zamjene jednog ili više sljeda u lokusu teškog lanca imunoglobulina miša s jednim ili više ljudskih imunoglobulinskih sljedova, pri čemu je poželjno da modifikacija lokusa teškog lanca imunoglobulina sadrži zamjenu varijabilnog genskog sljeda endogenog teškog lanca s humanim varijabilnim genskim sljedom endogenog teškog lanca, i još poželjnije da modifikacija lokusa teškog lanca imunoglobulina sadrži zamjenu jednog ili više endogenih genskih segmenata teških lanaca V (VH) s jednim ili više humanih genskih segmenata teških lanaca V (VH).
4. Postupak za modificiranje lokusa mišjeg teškog lanca imunoglobulina, naznačen time, da sadrži: (a) stvaranje prve modifikacije lokusa mišjeg teškog lanca imunoglobulina, što rezultira uklanjanjem endogene mišje ADAM6 aktivnosti u muških miševa; i, (b) izvođenje druge modifikacije miša kojom se dodaju sljedove nukleinskih kiselina koji omogućavaju mišu ADAM6 aktivnost koja je funkcionalna kod muškog miša, pri čemu je poželjno da se sljedovi nukleinskih kiselina u koraku (b) dodaju na ektopičnom položaju, a navedeni sljed nukleinske kiseline kodira mišji ADAM6a protein ili njegov ortologni ili homologni ili funkcionalni fragment, i mišji ADAM6b protein ili njegov ortologni ili homologni ili funkcionalni fragment.
5. Postupak prema zahtjevu 4, naznačen time, da prva modifikacija sadrži umetanje jedne ili više ljudskih imunoglobulinskih sekvenci ili da prvamodifikacija sadrži zamjenu jedne ili više sekvenci u mišjem lokusu teškog lanca imunoglobulina s jednim ili više ljudskih imunoglobulinskih sekvenci, pri čemu je poželjno da prva modifikacija sadrži zamjenu varijabilnog genskog sljeda endogenog teškog lanca s humanim varijabilnim genskim sljedom teškog lanca, i još poželjnije je da prva modifikacija sadrži zamjenu jednog ili više endogenih VH genskih segmenata s jednim ili više humanih genskih segmenata VH.
6. Postupak u skladu s bilo kojim od patentnih zahtjeva 4 do 5, naznačen time, da se prva i druga modifikacija odvijaju simultano.
7. Izolirana stanica ili tkivo izolirano iz miša, naznačeno time, da je u skladu sa bilo kojim od zahtjeva 1 do 3.
8. Upotreba miša u skladu s patentnim zahtjevom 3, naznačena time, da je namijenjena za generiranje(i) himernog antitijela, a navedeno himerno antitijelo sadrži humane varijabilne regije i mišje konstantne regije,(ii) potpuno humano antitijelo,(iii) potpuno humani Fab fragment, i / ili(iv) potpuno humani F(ab)2 fragment.
9. Postupak za proizvodnju himernog antitijela specifičnog za antigena, naznačen time, da obuhvaća korake:a) imuniziranje miša u skladu s patentnim zahtjevom 3 s antigenom;b) izoliranje najmanje jedne stanice s miša koji proizvodi himerno antitijelo specifično za antigen, a navedeno himerno antitijelo humane varijabilne regije i mišje konstantne regije; i c) kultiviranje barem jedne stanice za proizvodnju himernih antitijela iz koraka b) i dobivanje navedenog himernog antitijela, pri čemu je poželjno da se uzgoj u koraku c) izvodi na najmanje jednoj stanici hibridoma generiranoj iz barem jedne stanice dobivene u koraku b).
10. Postupak za generiranje potpuno ljudskog antitijela specifičnog za antigen, naznačen time, da sadrži sljedeće korake:a) imuniziranje miša s antigenom u skladu s patentnim zahtjevom 3;b) izoliranje najmanje jedne stanice od miša za proizvodnju himernog antitijela specifičnog za antigen, navedeno himerno antitijelo sadrži varijabilne regije čovjeka i konstantne regije miša;c) generiranje barem jedne stanice za proizvodnju potpuno ljudskog antitijela izvedenog iz himernog antitijela iz koraka b) i specifičnog za antigen; id) uzgoj barem jedne stanice za proizvodnju potpuno ljudskog antitijela iz koraka c), i dobivanje navedenog potpuno ljudskog antitijela.
11. Postupak prema bilo kojem od zahtjeva 9 i 10, naznačen time, da je najmanje jedna stanica iz koraka b) splenocit ili B stanica.
12. Postupak prema bilo kojem od zahtjeva 9 do 11, naznačen time, da je antitijelo monoklonsko antitijelo.
13. Postupak prema bilo kojem od zahtjeva 9 do12, naznačen time, da se imunizacija s antigenom iz koraka a) provodi s pomoću proteina, DNA, kombinacije DNA i proteina, ili stanice koje eksprimiraju antigen.
14. Sekvenca nukleinske kiseline koja kodira mišji protein ADAM6a ili njegov ortologni ili homologni ili funkcionalni fragment koji je funkcionalan kod mužjaka miša, i mišji protein ADAM6b ili njegov ortolog ili homolog ili funkcionalni fragment koji je funkcionalan u mužjaka miša, naznačen time, da je namijenjen za uporabu u obnovi ili povećanju plodnosti u mužjaka miša koji ima genom koji sadrži modifikaciju lokusa teškog lanca imunoglobulina, pri čemu modifikacija smanjuje ili otklanja djelovanje endogene ADAM6 funkcije, koja je povezana sa smanjenjem plodnosti kod mužjaka miševa, i pri čemu će navedena sekvenca nukleinske kiseline biti integrirana u genom miša, na endogeni imunoglobulinski lokus ili na položajima različitim od endogenog imunoglobulinskog lokusa.
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