HRP20120522T1 - Modificirani fgf-21 polipeptidi i njihova uporaba - Google Patents

Modificirani fgf-21 polipeptidi i njihova uporaba Download PDF

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HRP20120522T1
HRP20120522T1 HRP20120522AT HRP20120522T HRP20120522T1 HR P20120522 T1 HRP20120522 T1 HR P20120522T1 HR P20120522A T HRP20120522A T HR P20120522AT HR P20120522 T HRP20120522 T HR P20120522T HR P20120522 T1 HRP20120522 T1 HR P20120522T1
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polypeptide
polypeptide according
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P. Cujec Thomas
Mariani Roberto
A. Hays Putnam Anna-Maria
M. Keefe William
Knudsen Nick
Ho Lillian
Pinkstaff Jason
Kraynov Vadim
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Ambrx
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Abstract

FGF-21 polipeptid koji obuhvaća sekvencu prikazanu u SEQ ID NO: 1-7, osim što je jedna aminokiselina na položaju 108 zamijenjena aminokiselinom koja nije prirodno kodirana (SEQ ID NO: 1 ili odgovarajuće aminokiseline u SEQ ID NO: 2-7), gdje je u vodi topljivi polimer povezan s aminokiselinom koja nije prirodno kodirana i prisutna je u FGF-21 polipeptidu. Patent sadrži još 35 patentnih zahtjeva.

Claims (36)

1. FGF-21 polipeptid koji obuhvaća sekvencu prikazanu u SEQ ID NO: 1-7, osim što je jedna aminokiselina na položaju 108 zamijenjena aminokiselinom koja nije prirodno kodirana (SEQ ID NO: 1 ili odgovarajuće aminokiseline u SEQ ID NO: 2-7), gdje je u vodi topljivi polimer povezan s aminokiselinom koja nije prirodno kodirana i prisutna je u FGF-21 polipeptidu.
2. FGF-21 polipeptid prema zahtjevu 1, gdje je polipeptid povezan s linkerom, polimerom ili biološki aktivnom molekulom.
3. FGF-21 polipeptid prema zahtjevu 1, gdje je polipeptid povezan s bifunkcionalnim polimerom, bifunkcionalnim linkerom ili barem jednim dodatnim FGF-2 polipeptidom.
4. FGF-21 polipeptid prema zahtjevu 3, gdje je bifunkcionalni linker ili polimer povezan na drugi polipeptid.
5. FGF-21 polipeptid prema zahtjevu 4, gdje je drugi polipeptid FGF-21 polipeptid.
6. FGF-21 polipeptid prema zahtjevu 1, gdje u vodi topljivi polimer obuhvaća poli(etilen glikol) dio.
7. FGF-21 polipeptid prema zahtjevu 1, gdje aminokiselina koja nije prirodno kodirana obuhvaća karbonilnu skupinu, aminooksi skupinu, hidrazinsku skupinu, hidrazidnu skupinu, semikarbazidnu skupinu, azidnu skupinu ili alkinsku skupinu.
8. FGF-21 polipeptid prema zahtjevu 7, gdje aminokiselina koja nije prirodno kodirana obuhvaća karbonilnu skupinu.
9. FGF-21 polipeptid prema zahtjevu 1, gdje u vodi topljivi polimer ima molekularnu težinu između oko 0.1 kDa i oko 100 kDa.
10. FGF-21 polipeptid prema zahtjevu 9, gdje u vodi topljivi polimer ima molekularnu težinu između oko 0.1 kDa i oko 50 kDa.
11. FGF-21 polipeptid prema zahtjevu 1, koji nastaje reakcijom FGF-21 polipeptida koji obuhvaća aminokiselinu koja sadrži karbonil s u vodi topljivim polimerom koji obuhvaća aminooksi, hidrazin, hidrazid ili semikarbazid skupinu.
12. FGF-21 polipeptid prema zahtjevu 11, gdje je aminooksi, hidrazin, hidrazid ili semikarbazid skupina povezana za u vodi topljivi polimer preko amidne veze.
13. FGF-21 polipeptid prema zahtjevu 1, koji nastaje reakcijom u vodi topljivog polimera koji obuhvaća karbonilnu skupinu s polipeptidom koji obuhvaća aminokiselinu koja nije prirodno kodirana i sadrži aminooksi, hidrazin, hidrazid ili semikarbazid skupinu.
14. FGF-21 polipeptid prema zahtjevu 1, gdje je u vodi topljivi polimer razgranati ili višekračni polimer.
15. FGF-21 polipeptid prema zahtjevu 14, gdje svaka grana u vodi topljivog polimera ima molekularnu težinu između oko 1 kDa i oko 100 kDa.
16. FGF-21 polipeptid prema zahtjevu 1, gdje aminokiselina koja nije prirodno kodirana sadrži saharidni dio.
17. FGF-21 polipeptid prema zahtjevu 2, gdje je linker, polimer, ili biološki aktivna molekula povezana za peptid preko saharidnog dijela.
18. Smjesa koja sadrži FGF-21 polipeptid prema zahtjevu 1 i farmaceutski prihvatljivi nosač.
19. FGF-21 polipeptid prema zahtjevu 1, kodira ga polinuklotid čija je sekvenca prikazana u SEQ ID NO:8, 9, 10, 11, 12, 13, ili 14, gdje taj polinukleotid obuhvaća selektor kodon.
20. FGF-21 polipeptid prema zahtjevu 19, gdje u vodi topljivi polimer sadrži poli(etilen glikol) dio.
21. FGF-21 polipeptid prema zahtjevu 19, gdje aminokiselina koja nije prirodno kodirana sadrži karbonilnu skupinu, aminooksi, hidrazid, hidrazin, semikarbazid, azid ili alkin.
22. FGF-21 polipeptid prema zahtjevu 20, gdje poli(etilen glikol) dio ima molekularnu težinu između oko 0.1 kDa i oko 100 kDa.
23. FGF-21 polipeptid prema zahtjevu 20, gdje je poli(etilen glikol) dio razgranati ili višekračni polimer.
24. Smjesa prema zahtjevu 23, gdje poli(etilen glikol) dio ima molekularnu težinu između oko 1 kDa i oko 100 kDa.
25. Smjesa koja sadrži FGF-21 polipeptid prema zahtjevu 19 i farmaceutski prihvatljivi nosač.
26. FGF-21 polipeptid prema zahtjevu 1, sadrži u vodi topljivi polimer povezan kovalentnom vezom za FGF-21 polipeptid na aminokiselini koja nije prirodno kodirana.
27. FGF-21 polipeptid prema zahtjevu 26, gdje u vodi topljivi polimer sadrži poli(etilen glikol) dio.
28. FGF-21 polipeptid prema zahtjevu 7 gdje je aminokiselina koja nije prirodno kodirana povezana za poli(etilen glikol) molekulu.
29. FGF-21 polipeptid prema zahtjevu 1, sadrži barem jedan linker, polimer, ili biološki aktivnu molekulu, gdje je taj linker, polimer, ili biološki aktivna molekula spojen za polipeptid preko funkcionalne skupine aminokiseline koja nije prirodno kodirana, a koja je ribosomalno ugrađena u polipeptid.
30. FGF-21 polipeptid prema zahtjevu 29, gdje je FGF-21 polipeptid monoPEGiliran.
31. FGF-21 polipeptid prema zahtjevu 1, sadrži linker, polimer, ili biološki aktivnu molekulu spojen za aminokiselinu koja nije prirodno kodirana, gdje ta aminokiselina koja nije prirodno kodirana je ribosomalno ugrađena u polipeptid.
32. FGF-21 polipeptid prema zahtjevu 31, gdje FGF-21 polipeptid sadrži jedan linker, polimer, ili biološki aktivnu molekulu.
33. FGF-21 polipeptid prema zahtjevu 1, gdje aminokiselina koja nije prirodno kodirana sadrži ketonsku skupinu.
34. FGF-21 polipeptid prema zahtjevu 1, gdje FGF-21 polipeptid sadrži sekvencu kako je prikazano u SEQ ID NO: 1 osim što je jedna aminokiselina na položaju 108 zamijenjena aminokiselinom koja nije prirodno kodirana.
35. FGF-21 polipeptid prema zahtjevu 1, gdje ta aminokiselina koja nije prirodno kodirana je para-acetil-fenilalanin.
36. FGF-21 polipeptid prema zahtjevu 1, gdje u vodi topljivi polimer je poli(etilen glikol) dio molekularne težine od 30kDa.
HRP20120522AT 2007-03-30 2008-03-19 Modificirani fgf-21 polipeptidi i njihova uporaba HRP20120522T1 (hr)

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