SI3027015T1 - Humanizirane il-4 in il-4r alfa živali - Google Patents

Humanizirane il-4 in il-4r alfa živali Download PDF

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SI3027015T1
SI3027015T1 SI201530162T SI201530162T SI3027015T1 SI 3027015 T1 SI3027015 T1 SI 3027015T1 SI 201530162 T SI201530162 T SI 201530162T SI 201530162 T SI201530162 T SI 201530162T SI 3027015 T1 SI3027015 T1 SI 3027015T1
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rodent
gene
human
humanized
exon
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SI201530162T
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Li-Hsien Wang
Yingzi Xue
Andrew J. Murphy
Sean Stevens
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Regeneron Pharmaceuticals, Inc.
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    • C07K14/52—Cytokines; Lymphokines; Interferons
    • C07K14/54—Interleukins [IL]
    • C07K14/5406—IL-4
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    • G01N33/5082—Supracellular entities, e.g. tissue, organisms
    • G01N33/5088—Supracellular entities, e.g. tissue, organisms of vertebrates
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2207/00—Modified animals
    • A01K2207/15—Humanized animals
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
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    • A—HUMAN NECESSITIES
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    • A—HUMAN NECESSITIES
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    • 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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    • A01K2267/03—Animal model, e.g. for test or diseases
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Claims (12)

  1. HUMANIZIRANE IL-4 IN IL-4R ALFA ŽIVALI Patentni zahtevki
    1. Glodavec, ki obsega zamenjavo genomskega fragmenta glodavskega gena IL-4Ra na endogenem glodavskem lokusu IL-4Ra z genomskim fragmentom humanega gena IL4-Ra, da se tvori humanizirani gen IL-4Ra, ki obsega iniciacijski kodon ATG kodirnega eksona 1 do kodirnega eksona 5 humanega gena IL-4Ra, ter kodirne eksone od 6 do 9 glodavskega gena IL-4Ra, pri čemer genomski fragment glodavskega gena IL-4Ra obsega iniciacijski kodon ATG kodirnega eksona 1 do kodirnega eksona 5 glodavskega gena IL-4Ra, ter pri čemer genomski fragment humanega gena IL-4Ra obsega iniciacijski kodon ATG kodirnega eksona 1 do kodirnega eksona 5 humanega gena IL-4Ra, ter pri čemer je ekspresija humaniziranega gena IL-4Ra pod nadzorom glodavskih IL-4Ra regulatornih elementov na endogenem glodavskem lokusu IL-4Ra.
  2. 2. Glodavec po zahtevku 1, pri čemer je glodavec miš ali podgana.
  3. 3. Glodavec po zahtevku 1, pri čemer je glodavec miš, ki ni zmožna ekspresije mišjega proteina IL-4Ra.
  4. 4. Glodavec po zahtevku 1, pri čemer glodavec izraža humani oziroma humanizirani protein IL-4.
  5. 5. Glodavec po zahtevku 4, pri čemer je glodavec miš, ki ne izraža mišjega proteina IL-4.
  6. 6. Glodavec po zahtevku 1, pri čemer glodavec obsega zamenjavo genomskega fragmenta glodavskega gena IL-4 na endogenem glodavskem lokusu IL-4 z genomskim fragmentom humanega gena IL-4, da se tvori humanizirani gen IL-4, pri čemer genomski fragment glodavskega gena IL-4 obsega iniciacijski kodon ATG eksona 1 do eksona 4 glodavskega gena IL-4, ter pri čemer genomski fragment humanega gena IL-4 obsega iniciacijski kodon ATG eksona 1 do eksona 4 humanega gena IL-4, ter pri čemer je ekspresija humaniziranega gena IL-4 pod nadzorom glodavskih IL-4 regulatornih elementov na endogenem glodavskem lokusu IL-4.
  7. 7. Glodavec po katerem koli izmed zahtevkov od 1 do 2, 4 in 6, ki je miš.
  8. 8. Postopek za ustvarjanje glodavca, ki obsega zamenjavo genomskega fragmenta glodavskega gena IL-4Ra na endogenem glodavskem lokusu IL-4Ra z genomskim fragmentom humanega gena IL-4Ra, da se tvori humanizirani gen IL-4Ra, ki obsega iniciacijski kodon ATG kodirnega eksona 1 do kodirnega eksona 5 humanega gena IL-4Ra, ter kodirne eksone od 6 do 9 glodavskega gena IL-4Ra, pri čemer genomski fragment glodavskega gena IL-4Ra obsega iniciacijski kodon ATG kodirnega eksona 1 do kodirnega eksona 5 glodavskega gena IL-4Ra, ter pri čemer genomski fragment humanega gena IL-4Ra obsega iniciacijski kodon ATG kodirnega eksona 1 do kodirnega eksona 5 humanega gena IL-4Ra, ter pri čemer je humanizirani gen IL-4Ra operativno povezan z glodavskimi IL-4Ra regulatornimi elementi na endogenem glodavskem lokusu IL-4Ra.
  9. 9. Postopek po zahtevku 8, pri čemer je glodavec miš ali podgana.
  10. 10. Postopek po zahtevku 8 ali 9, pri čemer je glodavec miš.
  11. 11. Postopek za presejanje za humani specifični antagonist IL-4 ali IL-4Ra, ki obsega naslednje: zagotavljanje dvojno humaniziranega glodavca IL-4 in IL-4Ra, kot je opredeljeno v zahtevku 6, induciranje vnetja pljuč pri navedenem glodavcu, dajanje sredstva navedenemu glodavcu, '*· *·f ··· ugotavljanje, ali se je s sredstvom zmanjšalo vnetje pljuč, ter prepoznavanje sredstva kot humanospecifičnega antagonista IL-4 ali IL-4Ra na osnovi njegove sposobnosti, da zmanjša vnetje pljuč, ter poljubno, pri čemer se obseg vnetja pljuč določi z meijenjem akumulacije sluzi v dihalnih poteh, z eozinofilnimi infiltracijskimi celicami v bronhoalveolarni tekočini za izpiranje in/ali popolnoma cirkulirajočim IgE.
  12. 12. Postopek za presejanje za humanega specifičnega antagonista IL-4 ali IL-4Ra, ki obsega naslednje: zagotavljanje dvojno humaniziranega glodavca IL-4 in IL-4Ra, kot je opredeljeno v zahtevku 6, induciranje vnetja kože pri navedenem glodavcu, dajanje sredstva navedenemu glodavcu, ugotavljanje, ali se je s sredstvom zmanjšalo vnetje kože, ter prepoznavanje sredstva kot humanospecifičnega antagonista IL-4 ali IL-4Ra na osnovi njegove sposobnosti, da zmanjša vnetje kože.
SI201530162T 2014-05-07 2015-05-07 Humanizirane il-4 in il-4r alfa živali SI3027015T1 (sl)

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US201461989757P 2014-05-07 2014-05-07
PCT/US2015/029638 WO2015171861A1 (en) 2014-05-07 2015-05-07 Humanized il-4 and il-4r alpha animals
EP15727106.5A EP3027015B1 (en) 2014-05-07 2015-05-07 Humanized il-4 and il-4r alpha animals

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