HRP20141192T1 - Humanizirani il-6 i receptor il-6 - Google Patents

Humanizirani il-6 i receptor il-6 Download PDF

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HRP20141192T1
HRP20141192T1 HRP20141192AT HRP20141192T HRP20141192T1 HR P20141192 T1 HRP20141192 T1 HR P20141192T1 HR P20141192A T HRP20141192A T HR P20141192AT HR P20141192 T HRP20141192 T HR P20141192T HR P20141192 T1 HRP20141192 T1 HR P20141192T1
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mouse
human
gene
genetically modified
humanized
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HRP20141192AT
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Li-Hsien Wang
Anthony T. Dore
Sean Stevens
Andrew J. Murphy
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Regeneron Pharmaceuticals, Inc.
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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
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • A01K67/0278—Knock-in vertebrates, e.g. humanised vertebrates
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
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    • 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
    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/5412—IL-6
    • 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
    • C07K14/715—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons
    • C07K14/7155—Receptors; Cell surface antigens; Cell surface determinants for cytokines; for lymphokines; for interferons for interleukins [IL]
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    • 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
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    • 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
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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/06—Animal cells or tissues; Human cells or tissues
    • C12N5/0602—Vertebrate cells
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    • C12N5/0606—Pluripotent embryonic cells, e.g. embryonic stem cells [ES]
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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
    • C12N5/10—Cells modified by introduction of foreign genetic material
    • C12N5/12—Fused cells, e.g. hybridomas
    • C12N5/16—Animal 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)
    • 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
    • A01K2217/07—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
    • 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; 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
    • A01K2267/02—Animal zootechnically ameliorated
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

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Claims (17)

1. Genetički modificirani miš koji sadrži zamjenu na lokusu endogenog miša IL-6 mišjeg gena koji kodira IL-6 sa ljudskim genom koji kodira ljudski IL-6, naznačen time da je ljudski gen koji kodira ljudski IL-6 pod kontrolom regulacijskih elemenata endogenog miša na lokusu endogenog miša IL-6.
2. Genetički modificirani miš prema zahtjevu 1, naznačen time da ljudski gen koji kodira ljudski IL-6 sadrži eksone 1 do 5 ljudskog IL-6 gena pronađene u bakterijskom umjetnom kromosomu CTD-2369M23.
3. Genetički modificirani miš prema zahtjevu 1, naznačen time da miš eksprimira mišji IL-6Rα.
4. Genetički modificirani miš prema zahtjevu 1, naznačen time da miš eksprimira humanizirani IL-6Rα pri čemu je endogeni mišji IL-6Rα gen zamijenjen ljudskom sekvencom koja sadrži sekvencu koja kodira ektodomenu za ljudski IL-6Rα.
5. Genetički modificirani miš prema zahtjevu 1, naznačen time da miš ne iskazuje značajku izabranu od plazmocitoze, glomeruloskleroze, glomerulonefritisa, zatajenja bubrega, hipergamaglobulinemiju, povišene megakariocite u slezeni, povišene megakariocite u koštanoj srži, splenomegaliju, uvećanje limfnih čvorova, kompaktne abnormalne stanice plazme, te njihove kombinacije.
6. Genetički modificirani miš prema zahtjevu 4, naznačen time da humanizirani IL-6Rα sadrži ljudsku ektodomenu.
7. Genetički modificirani miš prema zahtjevu 6, naznačen time da humanizirani IL-6Rα sadrži mišju transmembransku domenu i mišju citoplazmatsku domenu.
8. Genetički modificirani miš prema zahtjevu 1, naznačen time da miš sadrži stanicu koja eksprimira IL-6Rα koji sadrži ljudsku ektodomenu na površini stanice.
9. Genetički modificirani miš, koji sadrži humanizaciju endogenog mišjeg IL-6Rα gena, naznačen time da se humanizacija sastoji od zamjene mišje IL-6Rα sekvence koja kodira ektodomenu sa ljudskom IL-6Rα sekvencom koja kodira ektodomenu na lokusu endogenog miša IL-6Rα, te pri čemu je humanizirani IL-6Rα gen pod kontrolom regulacijskih elemenata endogenog miša.
10. Genetički modificirani miš prema zahtjevu 9, naznačen time da je granična mišja sekvenca koja sadrži mišje eksone 1 do 8 zamijenjena sa graničnim genomskim fragmentom ljudske IL-6Rα sekvence koja kodira ljudsku ektodomenu IL-6Rα.
11. Genetički modificirani miš prema zahtjevu 10, naznačen time da je granični genomski fragment ljudske IL-6Rα sekvence koja kodira ektodomenu pronađen u bakterijskom umjetnom kromosomu CTD-2192J23.
12. Genetički modificirani miš prema zahtjevu 9, naznačen time da dodatno sadrži humanizirani IL-6 gen koji sadrži zamjenu na endogenom lokusu mišjeg IL-6 za mišji gen koji kodira IL-6 s ljudskim genom koji kodira ljudski IL-6.
13. Genetički modificirani miš prema zahtjevu 12, naznačen time da je humanizirani IL-6 gen pod kontrolom regulacijskih elemenata endogenog miša.
14. Postupak za stvaranje humaniziranog miša, naznačen time da sadrži zamjenu sekvence mišjeg gena koji kodira mišji IL-6 sa ljudskim genom koji kodira ljudski IL-6 tako da je ljudski IL-6 gen pod kontrolom regulacijskih elemenata endogenog miša.
15. Postupak za stvaranje humaniziranog miša, naznačen time da sadrži zamjenu svih mišjih eksona koji kodiraju sekvence ektodomene za mišji IL-6Rα sa ljudskim genomskim fragmentom koji kodira ljudsku ektodomenu IL-6Rα da se dobije humanizirani IL-6Rα gen, pri čemu je humanizirani IL-6Rα gen pod kontrolom regulacijskih elemenata endogenog miša.
16. Genetički modificirani miš koji sadrži humanizirani IL-6Rα gen koji sadrži zamjenu mišje sekvence koja kodira ektodomenu sa ljudskom sekvencom ektodomene, naznačen time da humanizirani IL-6Rα gen sadrži mišju transmembransku sekvencu i mišju citoplazmatsku sekvencu; pri čemu miš dodatno sadrži gen koji kodira ljudski IL-6, pri čemu su geni koji kodiraju ljudski IL-6 i humanizirani IL-6Rα pod kontrolom regulacijskih elemenata endogenog miša.
17. Genetički modificirani miš prema zahtjevu 16, naznačen time da miš ne eksprimira mišji IL-6Rα i ne eksprimira mišji IL-6.
HRP20141192AT 2011-10-28 2014-12-10 Humanizirani il-6 i receptor il-6 HRP20141192T1 (hr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201161552900P 2011-10-28 2011-10-28
US201161556579P 2011-11-07 2011-11-07
PCT/US2012/062379 WO2013063556A1 (en) 2011-10-28 2012-10-29 Humanized il-6 and il-6 receptor
EP12795905.4A EP2663575B1 (en) 2011-10-28 2012-10-29 Humanized il-6 and il-6 receptor

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EP (2) EP2818478B1 (hr)
JP (2) JP6120451B2 (hr)
KR (2) KR102234632B1 (hr)
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AU (1) AU2015207889B2 (hr)
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