HRP20191033T1 - Nukleinska kiselina koja sadrži ili kodira za histon peteljka-omča i poli(a) sekvencu ili poliadenilacijski signal za povećanje ekspresije kodiranog tumorskog antigena - Google Patents
Nukleinska kiselina koja sadrži ili kodira za histon peteljka-omča i poli(a) sekvencu ili poliadenilacijski signal za povećanje ekspresije kodiranog tumorskog antigena Download PDFInfo
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- HRP20191033T1 HRP20191033T1 HRP20191033TT HRP20191033T HRP20191033T1 HR P20191033 T1 HRP20191033 T1 HR P20191033T1 HR P20191033T T HRP20191033T T HR P20191033TT HR P20191033 T HRP20191033 T HR P20191033T HR P20191033 T1 HRP20191033 T1 HR P20191033T1
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Claims (21)
1. Komplet ili komplet dijelova koji sadrži:
A) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen NY-ESO-1, ili njegov fragment;
B) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen 5T4, ili njegov fragment;
C) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen survivin, ili njegov fragment;
D) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen MAGE-C1, ili njegov fragment; i
E) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen MAGE-C2, ili njegov fragment,
pri čemu fragment od NY-ESO-1, 5T4, survivina, MAGE-C1 ili MAGE-C2 ima duljinu od barem šest aminokiselinskih ostataka;
pri čemu svaka nukleinska kiselina A, B, C, D ili E – u smjeru 5' do 3' - sadrži ili kodira za
i)
a) kodirajuću regiju,
b) barem jedan histon peteljka-omča, i
c) poli(A) sekvencu;
ili
ii)
a) kodirajuću regiju,
b) poli(A) sekvencu, i
c) barem jedan histon peteljka-omča;
pri čemu je barem jedan histon peteljka-omča u i) ili ii) odabran iz sljedećih formula (I) ili (II):
formula (I) (sekvenca peteljka-omča bez graničnih elemenata peteljke):
formula (II) (sekvenca peteljka-omča s graničnim elementima peteljke):
pri čemu:
granični elementi peteljke1 ili peteljke2 N1-6 je uzastopna sekvenca od 1 do 6, poželjno od 2 do 6, poželjnije od 2 do 5, čak poželjnije od 3 do 5, najpoželjnije od 4 do 5 ili 5 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C, ili njihovog nukleotidnog analoga;
peteljka1 [N0-2GN3-5] je obrnuto komplementarna ili djelomično obrnuto komplementarna s elementom peteljka2, i uzastopna je sekvenca od 5 do 7 nukleotida;
pri čemu N0-2 je uzastopna sekvenca od 0 do 2, poželjno od 0 do 1, poželjnije od 1 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga;
pri čemu N3-5 je uzastopna sekvenca od 3 do 5, poželjno od 4 do 5, poželjnije od 4 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga, i
pri čemu G je gvanozin ili njegov analog, te može biti po izboru zamijenjen s citidinom ili njegovim analogom, pod uvjetom da je njegov komplementarni nukleotid citidin u peteljki2 zamijenjen s gvanozinom;
sekvenca omče [N0-4(U/T)N0-4] je smještena između elemenata peteljka1 i peteljka2, i uzastopna je sekvenca od 3 do 5 nukleotida, poželjnije od 4 nukleotida;
pri čemu svaki N0-4 je neovisno od drugog uzastopna sekvenca od 0 do 4, poželjno od 1 do 3, poželjnije od 1 do 2 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga; i
pri čemu U/T predstavlja uridin, ili po izboru timidin;
peteljka2 [N3-5CN0-2] je obrnuto komplementarna ili djelomično obrnuto komplementarna s elementom peteljka1, i uzastopna je sekvenca od 5 do 7 nukleotida;
pri čemu N3-5 je uzastopna sekvenca od 3 do 5, poželjno od 4 do 5, poželjnije od 4 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga;
pri čemu N0-2 je uzastopna sekvenca od 0 do 2, poželjno od 0 do 1, poželjnije od 1 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga; i
pri čemu C je citidin ili njegov analog, i može biti po izboru zamijenjen gvanozinom ili njegovim analogom pod uvjetom da je njegov komplementarni nukleotidni gvanozin u peteljka1 je zamijenjen s citidinom;
pri čemu
peteljka1 i peteljka2 su sposobne za međusobno sparivanje baza
formiranje obrnuto komplementarne sekvence, pri čemu se sparivanje baza može pojaviti između peteljke1 i peteljke2, ili
formiranje djelomično obrnuto komplementarne sekvence, pri čemu se nekompletno sparivanje baza može pojaviti između peteljke1 i peteljke2; i
pri čemu se barem jedan histon peteljka-omča veže na vezujući protein peteljka-omča (SLBP); i
pri čemu svaka nukleinska kiselina A, B, C, D ili E nadalje sadrži ili kodira za poli(C) sekvencu koja sadrži barem 10 citidin nukleotida.
2. Komplet ili komplet dijelova prema zahtjevu 1 naznačen time što dodatno sadrži nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju koja kodira tumorski antigen, pri čemu tumorski antigen je melanocitno-specifični antigen, antigen raka testisa ili tumorski-specifični antigen, poželjno CT-X antigen, ne-X CT-antigen, vezujući partner za CT-X antigen ili vezujući partner za ne-X CT-antigen ili tumorski-specifični antigen, poželjnije CT-X antigen, vezujući partner za ne-X CT-antigen ili tumorski-specifični antigen ili fragment navedenog tumorskog antigena, pri čemu fragment ima duljinu od barem šest aminokiselinskih ostataka.
3. Komplet ili komplet dijelova prema zahtjevu 1 ili zahtjevu 2 naznačen time što dodatno sadrži nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju koja kodira tumorski antigen, pri čemu je tumorski antigen odabran s popisa koji sadrži:
707-AP, 9D7, AFP, AlbZIP HPG1, alfa-5-beta-1-integrin, alfa-5-beta-6-integrin, alfa-actinin-4/m, alfa-metilacil-koenzim A racemaza, ART-4, ARTC1/m, B7H4, BAGE-1, BCL-2, bcr/abl, beta-katenin/m, BING-4, BRCA1/m, BRCA2/m, CA 15-3/CA 27-29, CA 19-9, CA72-4, CA125, kalretikulin, CAMEL, CASP-8/m, katepsin B, katepsin L, CD19, CD20, CD22, CD25, CDE30, CD33, CD4, CD52, CD55, CD56, CD80, CDC27/m, CDK4/m, CDKN2A/m, CEA, CLCA2, CML28, CML66, COA-1/m, protein sličan koaktozinu, kolaž XXIII, COX-2, CT-9/BRD6, Cten, ciklin B1, ciklin D1, cyp-B, CYPB1, DAM-10, DAM-6, DEK-CAN, EFTUD2/m, EGFR, ELF2/m, EMMPRIN, EpCam, EphA2, EphA3, ErbB3, ETV6-AML1, EZH2, FGF-5, FN, Frau-1, G250, GAGE-1, GAGE-2, GAGE-3, GAGE-4, GAGE-5, GAGE-6, GAGE7b, GAGE-8, GDEP, GnT-V, gp100, GPC3, GPNMB/m, HAGE, HAST-2, hepsin, Her2/neu, HERV-K-MEL, HLA-A*0201-R17I, HLA-A11/m, HLA-A2/m, HNE, homeoboks NKX3.1, HOM-TES-14/SCP-1, HOM-TES-85, HPV-E6, HPV-E7, HSP70-2M, HST-2, hTERT, iCE, IGF-1R, IL-13Ra2, IL-2R, IL-5, receptor nezrelog laminina, kallikrein-2, kallikrein-4, Ki67, KIAA0205, KIAA0205/m, KK-LC-1, K-Ras/m, LAGE-A1, LDLR-FUT, MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A9, MAGE-A10, MAGE-A12, MAGE-B1, MAGE-B2, MAGE-B3, MAGE-B4, MAGE-B5, MAGE-B6, MAGE-B10, MAGE-B16, MAGE-B17, MAGE-C3, MAGE-D1, MAGE-D2, MAGE-D4, MAGE-E1, MAGE-E2, MAGE-F1, MAGE-H1, MAGEL2, mamaglobin A, MART-1/melan-A, MART-2, MART-2/m, matrični protein 22, MC1R, M-CSF, ME1/m, mezotelin, MG50/PXDN, MMP11, MN/CA IX-antigen, MRP-3, MUC-1, MUC-2, MUM-1/m, MUM-2/m, MUM-3/m, miozin klase I/m, NA88-A, N-acetilglokozaminiltransferazu-V, Neo-PAP, Neo-PAP/m, NFYC/m, NGEP, NMP22, NPM/ALK, N-Ras/m, NSE, OA1, OFA-iLRP, OGT, OGT/m, OS-9, OS-9/m, osteokalcin, osteopontin, p15, p190 minor bcr-abl, p53, p53/m, PAGE-4, PAI-1, PAI-2, PAP, PART-1, PATE, PDEF, Pim-1-Kinase, Pin-1, Pml/PARalfa, POTE, PRAME, PRDX5/m, prostein, proteinase-3, PSA, PSCA, PSGR, PSM, PSMA, PTPRK/m, RAGE-1, RBAF600/m, RHAMM/CD168, RU1, RU2, S-100, SAGE, SART-1, SART-2, SART-3, SCC, SIRT2/m, Sp17, SSX-1, SSX-2/HOM-MEL-40, SSX-4, STAMP-1, STEAP-1, survivin-2B, SYT-SSX-1, SYT-SSX-2, TA-90, TAG-72, TARP, TEL-AML1, TGFbeta, TGFbetaRII, TGM-4, TPI/m, TRAG-3, TRG, TRP-1, TRP-2/6b, TRP/INT2, TRP-p8, tirozinaza, UPA, VEGFR1, VEGFR-2/FLK-1, WT1 i imunoglobulinski idiotip limfoidne krvne stanice ili T-stanični receptorski idiotip limfoidne krvne stanice, ili fragment navedenog tumorskog antigena, pri čemu fragment ima duljinu od barem šest aminokiselinskih ostataka.
4. Komplet ili komplet dijelova prema zahtjevima 1 do 3, naznačen time što je barem jedan histon peteljka omča heterologan za kodirajuću regiju, poželjno, pri čemu kodirajuća regija ne kodira histonski protein ili fragment, derivat njegove varijante koji ima histonsku ili histonski sličnu funkciju.
5. Komplet ili komplet dijelova prema bilo kojem od zahtjeva 1 do 4, naznačen time što kodirajuća regija ne kodira reporterski protein ili marker ili selektivni protein, pri čemu reporterski protein ili marker ili selektivni protein nije NY-ESO-1, 5T4, survivin, MAGE-C1, MAGE-C2 ili tumorski antigen kako je definirano u zahtjevu 2 ili 3.
6. Komplet ili komplet dijelova prema bilo kojem od zahtjeva 1 do 5, naznačen time što nukleinska kiselina je RNA, poželjno mRNA.
7. Komplet ili komplet dijelova prema bilo kojem od zahtjeva 1 do 6, naznačen time što je barem jedan histon peteljka-omča odabran od barem jedne od slijedećih formula (Ia) ili (IIa):
formula (Ia) (sekvenca peteljka-omča bez graničnih elemenata peteljke)
formula (IIa) (sekvenca peteljka-omča s graničnim elementima peteljke).
8. Komplet ili komplet dijelova prema bilo kojem od zahtjeva 1 do 7, naznačen time što poli(A) sekvenca obuhvaća sekvencu od oko 25 do oko 400 adenozinskih nukleotida, poželjno sekvencu od oko 50 do oko 400 adenozinskih nukleotida, poželjnije sekvencu od oko 50 do oko 300 adenozinskih nukleotida, čak poželjnije sekvencu od oko 50 do oko 250 adenozinskih nukleotida, najpoželjnije sekvencu od oko 60 do oko 250 adenozinskih nukleotida.
9. Komplet ili komplet dijelova prema bilo kojem od zahtjeva 1 do 8, naznačen time što je nukleinska kiselina modificirana nukleinska kiselina, naročito stabilizirana nukleinska kiselina.
10. Komplet ili komplet dijelova prema bilo kojem od zahtjeva 1 do 9, naznačen time što
se nukleinska kiselina C sastoji od sekvence nukleinske kiseline prema SEQ ID NO: 57; i/ili
se nukleinska kiselina D sastoji od sekvence nukleinske kiseline prema SEQ ID NO: 58.
11. Pripravak naznačen time što sadrži nukleinske kiseline kao što je definirano u bilo kojem od patentnih zahtjeva 1 do 10 s obzirom na komplet ili komplet dijelova.
12. Komplet ili komplet dijelova prema bilo kojem od zahtjeva 1 do 10;
te je komplet ili komplet dijelova naznačen time što sadrži:
A) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen NY-ESO-1, ili njegov fragment;
B) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen 5T4, ili njegov fragment;
C) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen survivin, ili njegov fragment;
D) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen MAGE-C1, ili njegov fragment; i
E) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen MAGE-C2, ili njegov fragment,
pri čemu fragment od NY-ESO-1, 5T4, survivin, MAGE-C1 ili MAGE-C2 ima duljinu od barem šest aminokiselinskih ostataka;
pri čemu svaka nukleinska kiselina A, B, C, D ili E – u smjeru 5' do 3' - sadrži ili kodira za
i)
a) kodirajuću regiju,
b) barem jedan histon peteljka-omča, i
c) poli(A) sekvencu;
ili
ii)
a) kodirajuću regiju,
b) poli(A) sekvencu, i
c) barem jedan histon peteljka-omča;
pri čemu je barem jedan histon peteljka-omča u i) ili ii) odabran iz sljedećih formula (I) ili (II):
formula (I) (sekvenca peteljka-omča bez graničnih elemenata peteljke):
formula (II) (sekvenca peteljka-omča s graničnim elementima peteljke):
pri čemu:
granični elementi peteljka1 ili peteljka2 N1-6 je uzastopna sekvenca od 1 do 6, poželjno od 2 do 6, poželjnije od 2 do 5, čak poželjnije od 3 do 5, najpoželjnije od 4 do 5 ili 5 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C, ili njihovog nukleotidnog analoga;
peteljka1 [N0-2GN3-5] je obrnuto komplementarna ili djelomično obrnuto komplementarna s elementom peteljka2, i uzastopna je sekvenca od 5 do 7 nukleotida;
pri čemu N0-2 je uzastopna sekvenca od 0 do 2, poželjno od 0 do 1, poželjnije od 1 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga;
pri čemu N3-5 je uzastopna sekvenca od 3 do 5, poželjno od 4 do 5, poželjnije od 4 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga, i
pri čemu G je gvanozin ili njegov analog, i može biti po izboru zamijenjen s citidinom ili njegovim analogom, pod uvjetom da je njegov komplementarni nukleotid citidin u peteljki2 zamijenjen s gvanozinom;
sekvenca omče [N0-4(U/T)N0-4] je smještena između elemenata peteljka1 i peteljka2, i uzastopna je sekvenca od 3 do 5 nukleotida, poželjnije od 4 nukleotida;
pri čemu svaki N0-4 je neovisno od drugog uzastopna sekvenca od 0 do 4, poželjno od 1 do 3, poželjnije od 1 do 2 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga; i
pri čemu U/T predstavlja uridin, ili po izboru timidin;
peteljka2 [N3-5CN0-2] je obrnuto komplementarna ili djelomično obrnuto komplementarna s elementom peteljka1, i uzastopna je sekvenca od 5 do 7 nukleotida;
pri čemu N3-5 je uzastopna sekvenca od 3 do 5, poželjno od 4 do 5, poželjnije od 4 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga;
pri čemu N0-2 je uzastopna sekvenca od 0 do 2, poželjno od 0 do 1, poželjnije od 1 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga; i
pri čemu C je citidin ili njegov analog, i može biti po izboru zamijenjen gvanozinom ili njegov analog pod uvjetom da je njegov komplementarni nukleotidni gvanozin u peteljka1 je zamijenjen s citidinom;
pri čemu
peteljka1 i peteljka2 su sposobne za međusobno sparivanje baza
formiranje obrnuto komplementarne sekvence, pri čemu se sparivanje baza može pojaviti između peteljke1 i peteljke2, ili
formiranje djelomično obrnuto komplementarne sekvence, pri čemu se nekompletno sparivanje baza može pojaviti između peteljke1 i peteljke2; i
pri čemu se barem jedan histon peteljka-omča veže na vezujući protein peteljka-omča (SLBP); ili
pripravak prema zahtjevu 11
za uporabu kao lijek.
13. Komplet ili komplet dijelova prema bilo kojem od zahtjeva 1 do 10;
te je komplet ili komplet dijelova naznačen time što sadrži:
A) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen NY-ESO-1, ili njegov fragment;
B) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen 5T4, ili njegov fragment;
C) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen survivin, ili njegov fragment;
D) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen MAGE-C1, ili njegov fragment; i
E) nukleinsku kiselinu koja sadrži ili kodira za kodirajuću regiju, pri čemu kodirajuća regija kodira barem jedan peptid ili protein, koji sadrži tumorski antigen MAGE-C2, ili njegov fragment,
pri čemu fragment od NY-ESO-1, 5T4, survivin, MAGE-C1 ili MAGE-C2 ima duljinu od barem šest aminokiselinskih ostataka;
pri čemu svaka nukleinska kiselina A, B, C, D ili E – u smjeru 5' do 3' - sadrži ili kodira za
i)
a) kodirajuću regiju,
b) barem jedan histon peteljka-omča, i
c) poli(A) sekvencu;
ili
ii)
a) kodirajuću regiju,
b) poli(A) sekvencu, i
c) barem jedan histon peteljka-omča;
pri čemu je barem jedan histon peteljka-omča u i) ili ii) odabran iz sljedećih formula (I) ili (II):
formula (I) (sekvenca peteljka-omča bez graničnih elemenata peteljke):
formula (II) (sekvenca peteljka-omča s graničnim elementima peteljke):
pri čemu:
granični elementi peteljka1 ili peteljka2 N1-6 je uzastopna sekvenca od 1 do 6, poželjno od 2 do 6, poželjnije od 2 do 5, čak poželjnije od 3 do 5, najpoželjnije od 4 do 5 ili 5 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C, ili njihovog nukleotidnog analoga;
peteljka1 [N0-2GN3-5] je obrnuto komplementarna ili djelomično obrnuto komplementarna s elementom peteljka2, i uzastopna je sekvenca od 5 do 7 nukleotida;
pri čemu N0-2 je uzastopna sekvenca od 0 do 2, poželjno od 0 do 1, poželjnije od 1 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga;
pri čemu N3-5 je uzastopna sekvenca od 3 do 5, poželjno od 4 do 5, poželjnije od 4 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga, i
pri čemu G je gvanozin ili njegov analog, i može biti po izboru zamijenjen s citidinom ili njegovim analogom, pod uvjetom da je njegov komplementarni nukleotid citidin u peteljki2 zamijenjen s gvanozinom;
sekvenca omče [N0-4(U/T)N0-4] je smještena između elemenata peteljka1 i peteljka2, i uzastopna je sekvenca od 3 do 5 nukleotida, poželjnije od 4 nukleotida;
pri čemu svaki N0-4 je neovisno od drugog uzastopna sekvenca od 0 do 4, poželjno od 1 do 3, poželjnije od 1 do 2 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga; i pri čemu U/T predstavlja uridin, ili po izboru timidin;
peteljka2 [N3-5CN0-2] je obrnuto komplementarna ili djelomično obrnuto komplementarna s elementom peteljka1, i uzastopna je sekvenca od 5 do 7 nukleotida;
pri čemu N3-5 je uzastopna sekvenca od 3 do 5, poželjno od 4 do 5, poželjnije od 4 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga;
pri čemu N0-2 je uzastopna sekvenca od 0 do 2, poželjno od 0 do 1, poželjnije od 1 N, pri čemu svaki N je neovisno od drugoga odabran od nukleotida koji je odabran od A, U, T, G i C ili njihovog nukleotidnog analoga; i
pri čemu C je citidin ili njegov analog, i može biti po izboru zamijenjen gvanozinom ili njegov analog pod uvjetom da je njegov komplementarni nukleotidni gvanozin u peteljka1 je zamijenjen s citidinom;
pri čemu
peteljka1 i peteljka2 su sposobne za međusobno sparivanje baza
formiranje obrnuto komplementarne sekvence, pri čemu se sparivanje baza može pojaviti između peteljke1 i peteljke2, ili
formiranje djelomično obrnuto komplementarne sekvence, pri čemu se nekompletno sparivanje baza može pojaviti između peteljke1 i peteljke2; i
pri čemu se barem jedan histon peteljka-omča veže na vezujući protein peteljka-omča (SLBP); ili
pripravak prema zahtjevu 11
za uporabu u liječenju raka ili tumorskih bolesti.
14. Komplet ili komplet dijelova ili pripravak za uporabu prema zahtjevu 13, naznačen time što rak ili tumorska bolest je rak pluća ne-malih stanica.
15. Farmaceutski pripravak naznačen time što sadrži nukleinske kiseline kao što je definirano bilo kojim od patentnih zahtjeva 1 do 10 u odnosu na komplet ili komplet dijelova ili pripravak kao što je definirano u zahtjevu 11 i po izboru farmaceutski prihvatljiv nosač.
16. Uporaba kompleta ili kompleta dijelova prema bilo kojem od zahtjeva 1 do 10 ili pripravak prema zahtjevu 11 za povećanje ekspresije navedenog kodiranog peptida ili proteina in vitro.
17. In vitro postupak za povećanje ekspresije kodiranog peptida ili proteina koji sadrži korake:
a) osiguravanje kompleta ili komplet dijelova prema bilo kojem od zahtjeva 1 do 10 ili pripravak prema zahtjevu 11,
b) primjenu ili davanje nukleinskih kiselina iz kompleta ili kompleta dijelova ili pripravka u ekspresijski sustav bez stanica, stanicu ili tkivo.
18. Nukleinska kiselina naznačena time što je odabrana iz skupine koju čine SEQ ID NO: 57 i SEQ ID NO: 58.
19. Farmaceutski pripravak naznačen time što nukleinsku kiselinu prema zahtjevu 18.
20. Nukleinska kiselina prema zahtjevu 18 ili farmaceutski pripravak prema zahtjevu 19 naznačena time što je za uporabu u liječenju raka ili tumorskih bolesti.
21. Nukleinska kiselina ili farmaceutski pripravak za uporabu prema zahtjevu 20, naznačena time što rak ili tumorska bolest je rak pluća ne-malih stanica.
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| Application Number | Priority Date | Filing Date | Title |
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| PCT/EP2012/000674 WO2013120500A1 (en) | 2012-02-15 | 2012-02-15 | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded tumour antigen |
| EP16001897.4A EP3178488B1 (en) | 2012-02-15 | 2013-02-15 | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded tumour antigen |
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| CN (2) | CN104105792B (hr) |
| AU (2) | AU2013220747B2 (hr) |
| BR (1) | BR112014017384A2 (hr) |
| CA (1) | CA2857560C (hr) |
| DK (1) | DK2814961T3 (hr) |
| ES (4) | ES2671393T3 (hr) |
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| LT (1) | LT3178488T (hr) |
| ME (1) | ME03484B (hr) |
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| RU (2) | RU2650795C2 (hr) |
| SG (3) | SG10201606787XA (hr) |
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| EP3578205A1 (en) | 2010-08-06 | 2019-12-11 | ModernaTX, Inc. | A pharmaceutical formulation comprising engineered nucleic acids and medical use thereof |
| WO2012019630A1 (en) | 2010-08-13 | 2012-02-16 | Curevac Gmbh | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded protein |
| US9464124B2 (en) | 2011-09-12 | 2016-10-11 | Moderna Therapeutics, Inc. | Engineered nucleic acids and methods of use thereof |
| WO2013120497A1 (en) | 2012-02-15 | 2013-08-22 | Curevac Gmbh | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded therapeutic protein |
| WO2013120499A1 (en) | 2012-02-15 | 2013-08-22 | Curevac Gmbh | Nucleic acid comprising or coding for a histone stem-loop and a poly (a) sequence or a polyadenylation signal for increasing the expression of an encoded pathogenic antigen |
| WO2013120498A1 (en) | 2012-02-15 | 2013-08-22 | Curevac Gmbh | Nucleic acid comprising or coding for a histone stem-loop and a poly(a) sequence or a polyadenylation signal for increasing the expression of an encoded allergenic antigen or an autoimmune self-antigen |
| RU2660565C2 (ru) | 2012-03-27 | 2018-07-06 | Кьюрвак Аг | Молекулы искусственной нуклеиновой кислоты, содержащие 5'utr гена top |
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