HRP20190227T1 - Životinje koje nisu ljudi, koje imaju humanizirani gen za protein za reguliranje signala - Google Patents

Životinje koje nisu ljudi, koje imaju humanizirani gen za protein za reguliranje signala Download PDF

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Publication number
HRP20190227T1
HRP20190227T1 HRP20190227TT HRP20190227T HRP20190227T1 HR P20190227 T1 HRP20190227 T1 HR P20190227T1 HR P20190227T T HRP20190227T T HR P20190227TT HR P20190227 T HRP20190227 T HR P20190227T HR P20190227 T1 HRP20190227 T1 HR P20190227T1
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Croatia
Prior art keywords
rodent
sirpα
gene
humanized
human
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HRP20190227TT
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Andrew J. Murphy
Gavin Thurston
Bindu Varghese
Cagen Gurer
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Regeneron Pharmaceuticals, Inc.
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Publication of HRP20190227T1 publication Critical patent/HRP20190227T1/hr

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Claims (15)

1. Glodavac čiji genom sadrži zamjenu egzona 2, 3 i 4 u glodavačkom genu SIRPα u endogenom glodavačkom lokusu SIRPα egzonima 2, 3 i 4 iz ljudskog gena SIRPα kako bi se dobilo humanizirani gen SIRPα, naznačen time što je navedeni humanizirani gen SIRPα operabilno povezan s glodavačkim SIRPα promotorom u navedenom endogenom glodavačkom lokusu SIRPα, te eksprimira u navedenom glodavcu humanizirani protein SIRPα, koji sadrži izvanstanični dio ljudskog proteina SIRPα kojeg kodira navedeni ljudski gen SIRPα i unutarstanični dio glodavačkog proteina SIRPα kojeg kodira navedeni glodavački gen SIRPα.
2. Glodavac u skladu s patentnim zahtjevom 1, naznačen time što humanizirani gen SIRPα sadrži egzone 1, 5, 6, 7 i 8 iz navedenog glodavačkog gena SIRPα.
3. Glodavac u skladu s patentnim zahtjevom 1 ili 2, naznačen time što navedeni ljudski protein SIRPα sadrži aminokiselinski slijed kao što je iznijeto u SEQ ID NO: 4.
4. Glodavac u skladu s patentnim zahtjevom 3, naznačen time što navedeni humanizirani protein SIRPα sadrži aminokiselinske ostatke 28-362 u SEQ ID NO: 4.
5. Glodavac u skladu s bilo kojim od patentnih zahtjeva 1-4, naznačen time što glodavac ne eksprimira glodavački protein SIRPα.
6. Izolirana glodavačka stanica ili tkivo čiji genom sadrži zamjenu egzona 2, 3 i 4 u glodavačkom genu SIRPα u endogenom glodavačkom lokusu SIRPα egzonima 2, 3 i 4 iz ljudskog gena SIRPα kako bi se dobilo humanizirani gen SIRPα, naznačen time što je navedeni humanizirani gen SIRPα operabilno povezan s glodavačkim SIRPα promotorom u navedenom endogenom glodavačkom lokusu SIRPα, te kodira humanizirani protein SIRPα, koji sadrži izvanstanični dio ljudskog proteina SIRPα kojeg kodira navedeni ljudski gen SIRPα i unutarstanični dio glodavačkog proteina SIRPα kojeg kodira navedeni glodavački gen SIRPα.
7. Izolirana stanica ili tkivo u skladu s patentnim zahtjevom 6, naznačeni time što humanizirani gen SIRPα sadrži egzone 1, 5, 6, 7 i 8 iz navedenog glodavačkog gena SIRPα.
8. Izolirana stanica ili tkivo u skladu s patentnim zahtjevom 6 ili 7, naznačeni time što stanica ili tkivo ne eksprimira glodavački protein SIRPα.
9. Izolirana glodavačka stanica u skladu s bilo kojim od patentnih zahtjeva 6-8, naznačen time što je glodavačka stanica glodavačka embrionska matična stanica.
10. Postupak dobivanja glodavca, naznačen time što se sastoji u: (a) zamjeni egzona 2, 3 i 4 u glodavačkom genu SIRPα u endogenom glodavačkom lokusu SIRPα u glodavačkoj stanici ES egzonima 2, 3 i 4 iz ljudskog gena SIRPα kako bi se dobilo humanizirani gen SIRPα, gdje je navedeni humanizirani gen SIRPα operabilno povezan s glodavačkim SIRPα promotorom u navedenom endogenom glodavačkom lokusu SIRPα, te kodira humanizirani protein SIRPα, koji sadrži izvanstanični dio ljudskog proteina SIRPα kojeg kodira navedeni ljudski gen SIRPα i unutarstanični dio glodavačkog proteina SIRPα kojeg kodira navedeni glodavački gen SIRPα; čime se dobije modificiranu glodavačku stanicu ES, koja sadrži navedeni humanizirani gen SIRPα; i (b) kreiranje glodavac uz upotrebu modificirane stanice ES dobivene u (a).
11. Postupak u skladu s patentnim zahtjevom 10, naznačen time što humanizirani gen SIRPα sadrži egzone 1, 5, 6, 7 i 8 iz navedenog glodavačkog gena SIRPα.
12. Postupak u skladu s patentnim zahtjevom 10 ili 11, naznačen time što navedeni ljudski protein SIRPα sadrži aminokiselinski slijed kao što je iznijeto u SEQ ID NO: 4.
13. Glodavac u skladu s patentnim zahtjevom 12, naznačen time što navedeni humanizirani protein SIRPα sadrži aminokiselinske ostatke 28-362 u SEQ ID NO: 4.
14. Postupak procjenjivanja terapijske djelotvornosti lijeka koji ciljano djeluje na ljudske stanice, naznačen time što se sastoji u: (a) osiguravanju glodavca u skladu s bilo kojim od patentnih zahtjeva 1-6 u kojeg se presađuje jednu ili više ljudskih stanica; (b) primjeni kandidatnog lijeka na navedenom glodavcu; i (c) praćenju ljudskih stanica u glodavcu kako bi se odredilo terapijsku djelotvornost kandidatnog lijeka.
15. Glodavac u skladu s bilo kojim od patentnih zahtjeva 1-5, izolirana glodavačka stanica ili tkivo u skladu s bilo kojim od patentnih zahtjeva 6-9 ili postupak u skladu s bilo kojim od patentnih zahtjeva 10-14, naznačeni time što je glodavac štakor.
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