HRP20231542T1 - Kimerni antigenski receptori koji ciljaju bcma i postupci njihove uporabe - Google Patents

Kimerni antigenski receptori koji ciljaju bcma i postupci njihove uporabe Download PDF

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HRP20231542T1
HRP20231542T1 HRP20231542TT HRP20231542T HRP20231542T1 HR P20231542 T1 HRP20231542 T1 HR P20231542T1 HR P20231542T T HRP20231542T T HR P20231542TT HR P20231542 T HRP20231542 T HR P20231542T HR P20231542 T1 HRP20231542 T1 HR P20231542T1
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car according
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HRP20231542TT
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Xiaohu FAN
Qiuchuan ZHUANG
Pingyan WANG
Lin Wang
Lei Yang
Jiaying HAO
Dan Zhao
Xian HE
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Legend Biotech Ireland Limited
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Publication of HRP20231542T1 publication Critical patent/HRP20231542T1/hr

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Claims (25)

1. Kimerni antigenski receptor (CAR) koji sadrži polipeptid koji sadrži: (a) izvanstaničnu domenu vezanja antigena koja sadrži jednostruko antitijelo (sdAb) prvog anti-B-staničkog sazrijevanja antigena (BCMA) koje sadrži VHH domenu koja sadrži aminokiselinsku sekvencu SEQ ID NO: 124 i drugo anti-BCMA sdAb koje sadrži VHH domenu koja sadrži aminokiselinsku sekvencu SEQ ID NO: 117; (b) transmembransku domenu; i (c) unutarstaničnu signalnu domenu.
2. CAR prema zahtjevu 1, naznačen time što je prvo anti-BCMA sdAb locirano na N-kraju ili C-kraju drugog anti-BCMA sdAb.
3. CAR prema zahtjevu 1 ili 2, naznačen time što su prvo anti-BCMA sdAb i drugo anti-BCMA sdAb spojeni jedno s drugim preko peptidnog veznika.
4. CAR prema zahtjevu 3, naznačen time što peptidni veznik nije duži od oko 50 aminokiselina.
5. CAR prema bilo kojem od zahtjeva 1 do 4, naznačen time što je transmembranska domena izvedena iz molekule odabrane iz skupine koju čine CD8α, CD4, CD28, CD137, CD80, CD86, CD152 i PD1.
6. CAR prema zahtjevu 5, naznačen time što je transmembranska domena izvedena iz CD8α ili CD28.
7. CAR prema bilo kojem od zahtjeva 1 do 6, naznačen time što unutarstanična signalna domena sadrži primarnu unutarstaničnu signalnu domenu imunološke efektorske stanice.
8. CAR prema zahtjevu 7, naznačen time što je primarna unutarstanična signalna domena izvedena iz CD3ζ.
9. CAR prema bilo kojem od zahtjeva 1 do 8, naznačen time što unutarstanična signalna domena sadrži ko-stimulacijsku signalnu domenu.
10. CAR prema zahtjevu 9, naznačen time što je ko-stimulacijska signalna domena izvedena iz ko-stimulacijske molekule odabrane iz skupine koju čine CD27, CD28, CD137, OX40, CD30, CD40, CD3, LFA-1, ICOS, CD2, CD7, LIGHT, NKG2C, B7-H3, ligandi CD83 i njihove kombinacije.
11. CAR prema zahtjevu 10, naznačen time što ko-stimulacijska signalna domena sadrži citoplazmatsku domenu CD28 i/ili citoplazmatsku domenu CD137.
12. CAR prema bilo kojem od zahtjeva 1 do 11, naznačen time što CAR nadalje sadrži zglobnu domenu koja se nalazi između C-kraja izvanstanične domene vezanja antigena i N-kraja transmembranske domene.
13. CAR prema zahtjevu 12, naznačen time što je zglobna domena izvedena iz CD8α.
14. CAR prema bilo kojem od zahtjeva 1 do 13, naznačen time što CAR nadalje sadrži signalni peptid koji se nalazi na N-kraju polipeptida.
15. CAR prema zahtjevu 14, naznačen time što je signalni peptid izveden iz CD8α.
16. CAR prema bilo kojem od zahtjeva 1 do 15 koji sadrži polipeptid koji sadrži aminokiselinsku sekvencu SEQ ID NO: 300.
17. Izolirana nukleinska kiselina koja sadrži sekvencu nukleinske kiseline koja kodira CAR prema bilo kojem od zahtjeva 1 do 16.
18. Izolirana nukleinska kiselina prema zahtjevu 17 koja sadrži nukleotidnu sekvencu SEQ ID NO: 338.
19. Vektor koji sadrži izoliranu nukleinsku kiselinu prema zahtjevu 17 ili 18.
20. Vektor prema zahtjevu 19 koji je lentivirusni vektor.
21. Projektirana imunološka efektorska stanica koja sadrži CAR prema bilo kojem od zahtjeva 1 do 16, izoliranu nukleinsku kiselinu prema zahtjevu 17 ili 18, ili vektor prema zahtjevu 19 ili 20.
22. Projektirana imunološka efektorska stanica prema zahtjevu 21, naznačena time što je modificirana imunološka efektorska stanica T stanica.
23. Farmaceutski pripravak koji sadrži modificiranu imunološku efektorsku stanicu prema zahtjevu 21 ili 22 i farmaceutski prihvatljiv nosač.
24. CAR kako je definiran u bilo kojem od zahtjeva 1 do 16 ili farmaceutski pripravak kako je definiran u zahtjevu 23 za uporabu u postupku liječenja raka kod pojedinca.
25. CAR ili farmaceutski pripravak za uporabu prema zahtjevu 24, naznačen time što je rak multipli mijelom.
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