HRP20240576T1 - Cd19 specifični kimerni antigenski receptor i njegova upotreba - Google Patents

Cd19 specifični kimerni antigenski receptor i njegova upotreba Download PDF

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HRP20240576T1
HRP20240576T1 HRP20240576TT HRP20240576T HRP20240576T1 HR P20240576 T1 HRP20240576 T1 HR P20240576T1 HR P20240576T T HRP20240576T T HR P20240576TT HR P20240576 T HRP20240576 T HR P20240576T HR P20240576 T1 HRP20240576 T1 HR P20240576T1
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HRP20240576TT
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Cècile SCHIFFER-MANNIOUI
Roman Galetto
Julianne Smith
Andrew Scharenberg
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Cellectis
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Priority claimed from PCT/US2013/040755 external-priority patent/WO2013176915A1/en
Application filed by Cellectis filed Critical Cellectis
Publication of HRP20240576T1 publication Critical patent/HRP20240576T1/hr

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Claims (16)

1. Pripravak za upotrebu u kombiniranoj terapiji koji sadrži: (a) konstruiranu T-stanicu koja eksprimira CD19-specifični kimerni antigenski receptor (CAR), koji sadrži najmanje jednu izvanstaničnu domenu vezanja liganda specifičnu za CD19, transmembransku domenu i najmanje jednu unutarstaničnu signalnu domenu; pri čemu navedena izvanstanična domena sadrži jednolančani FV fragment izveden iz monoklonskog protutijela 4G7, specifičan za CD19, navedeni jednolančani FV fragment sadrži varijabilni fragment CD19 monoklonskog protutijela 4G7 imunoglobulinskog gama 1 teškog lanca prema SEQ ID NO: 3 i varijabilni fragment CD19 monoklonskog protutijela 4G7 imunoglobulinskog kapa lakog lanca prema SEQ ID NO: 4 ili SEQ ID NO: 5; i (b) protutijelo alemtuzumab.
2. Pripravak za upotrebu prema zahtjevu 1, naznačen time što navedeni jednolančani FV fragment sadrži aminokiselinsku sekvencu SEQ ID NO: 7 ili 8.
3. Pripravak za upotrebu prema zahtjevu 1 ili 2, naznačen time što najmanje jedna unutarstanična signalna domena CD19-specifičnog CAR-a je CD3 zeta signalna domena koja sadrži aminokiselinsku sekvencu prema SEQ ID NO: 10.
4. Pripravak za upotrebu prema bilo kojem od zahtjeva 1 do 3, naznačen time što transmembranska domena CD19-specifičnog CAR sadrži transmembranu ljudskog CD8 alfa lanca i stabljičnu domenu koja sadrži aminokiselinsku sekvencu SEQ ID NO: 13.
5. Pripravak za upotrebu prema bilo kojem od zahtjeva 1 do 4, naznačen time što CAR specifičan za CD19 sadrži drugu unutarstaničnu signalnu domenu.
6. Pripravak za upotrebu prema zahtjevu 5, naznačen time što druga unutarstanična signalna domena sadrži aminokiselinsku sekvencu SEQ ID NO: 11.
7. Pripravak za upotrebu prema zahtjevu 1, naznačen time što CD19-specifični CAR sadrži aminokiselinsku sekvencu SEQ ID NO: 14 ili 15.
8. Pripravak za upotrebu prema bilo kojem od zahtjeva 1 do 7, naznačen time što je konstruirana T-stanica genetski modificirana inaktivacijom gena koji kodira TCRalfa, TCRbeta, CD52, GR, PD1 ili CTLA-4.
9. Konstruirana T-stanica koja eksprimira CD19-specifični kimerni antigenski receptor (CAR), koji sadrži najmanje jednu izvanstaničnu domenu vezanja liganda specifičnu za CD19, transmembransku domenu i najmanje jednu unutarstaničnu signalnu domenu; pri čemu navedena izvanstanična domena sadrži jednolančani FV fragment izveden iz monoklonskog protutijela 4G7, specifičan za CD19, navedeni jednolančani FV fragment sadrži varijabilni fragment CD19 monoklonskog protutijela 4G7 imunoglobulinskog gama 1 teškog lanca prema SEQ ID NO: 3 i varijabilni fragment CD19 monoklonskog protutijela 4G7 imunoglobulinskog kapa lakog lanca prema SEQ ID NO: 4 ili SEQ ID NO: 5, za upotrebu u kombinaciji s protutijelom alemtuzumab u postupku liječenja raka kod subjekta kojem je to potrebno, te postupak uključuje: davanje subjektu protutijela alemtuzumaba; i davanje subjektu konstruirane T-stanice.
10. Konstruirana T-stanica za upotrebu prema zahtjevu 9, naznačena time što navedeni jednolančani FV fragment sadrži aminokiselinsku sekvencu prema SEQ ID NO: 7 ili 8.
11. Konstruirana T-stanica za upotrebu prema zahtjevu 9 ili 10, naznačena time što je najmanje jedna unutarstanična signalna domena CD19-specifičnog CAR-a CD3 zeta signalna domena koja sadrži aminokiselinsku sekvencu prema SEQ ID NO: 10.
12. Konstruirana T-stanica za upotrebu prema bilo kojem od zahtjeva 9 do 11, naznačena time što transmembranska domena CD19-specifičnog CAR-a sadrži transmembranu ljudskog CD8 alfa lanca i stabljičnu domenu koja sadrži aminokiselinsku sekvencu prema SEQ ID NO: 13.
13. Konstruirana T-stanica za upotrebu prema bilo kojem od zahtjeva 9 do 12, naznačena time što CAR specifičan za CD19 sadrži drugu unutarstaničnu signalnu domenu.
14. Konstruirana T-stanica za upotrebu prema zahtjevu 13, naznačena time što druga unutarstanična signalna domena sadrži aminokiselinsku sekvencu prema SEQ ID NO: 11.
15. Konstruirana T-stanica za upotrebu prema zahtjevu 9, naznačena time što CD19-specifični CAR sadrži aminokiselinsku sekvencu prema SEQ ID NO: 14 ili 15.
16. Konstruirana T-stanica za upotrebu prema bilo kojem od zahtjeva 9 do 15, naznačena time što je projektirana T-stanica genetski modificirana inaktivacijom gena koji kodira TCRalfa, TCRbeta, CD52, GR, PD1 ili CTLA-4.
HRP20240576TT 2013-05-13 2014-05-12 Cd19 specifični kimerni antigenski receptor i njegova upotreba HRP20240576T1 (hr)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
PCT/US2013/040755 WO2013176915A1 (en) 2012-05-25 2013-05-13 Methods for engineering allogeneic and immunosuppressive resistant t cell for immunotherapy
US13/892,805 US11603539B2 (en) 2012-05-25 2013-05-13 Methods for engineering allogeneic and immunosuppressive resistant T cell for immunotherapy
PCT/US2013/040766 WO2013176916A1 (en) 2012-05-25 2013-05-13 Use of pre t alpha or functional variant thereof for expanding tcr alpha deficient t cells
US201361888259P 2013-10-08 2013-10-08
EP19161861.0A EP3546572B9 (en) 2013-05-13 2014-05-12 Cd19 specific chimeric antigen receptor and uses thereof

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