HRP20221474T1 - Cjepiva protiv virusa hepatitisa b - Google Patents
Cjepiva protiv virusa hepatitisa b Download PDFInfo
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- HRP20221474T1 HRP20221474T1 HRP20221474TT HRP20221474T HRP20221474T1 HR P20221474 T1 HRP20221474 T1 HR P20221474T1 HR P20221474T T HRP20221474T T HR P20221474TT HR P20221474 T HRP20221474 T HR P20221474T HR P20221474 T1 HRP20221474 T1 HR P20221474T1
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- 229960005486 vaccine Drugs 0.000 title claims 5
- 241000700721 Hepatitis B virus Species 0.000 title 1
- 108090000623 proteins and genes Proteins 0.000 claims 29
- 239000002773 nucleotide Substances 0.000 claims 28
- 125000003729 nucleotide group Chemical group 0.000 claims 28
- 102000004169 proteins and genes Human genes 0.000 claims 28
- 230000000890 antigenic effect Effects 0.000 claims 26
- 239000012634 fragment Substances 0.000 claims 25
- 239000013603 viral vector Substances 0.000 claims 24
- 241000712891 Arenavirus Species 0.000 claims 19
- 102100031673 Corneodesmosin Human genes 0.000 claims 13
- 101710139375 Corneodesmosin Proteins 0.000 claims 13
- 230000004927 fusion Effects 0.000 claims 13
- 210000004027 cell Anatomy 0.000 claims 12
- 208000015181 infectious disease Diseases 0.000 claims 11
- 230000002458 infectious effect Effects 0.000 claims 11
- 108700026244 Open Reading Frames Proteins 0.000 claims 9
- 125000003275 alpha amino acid group Chemical group 0.000 claims 8
- 241000712899 Lymphocytic choriomeningitis mammarenavirus Species 0.000 claims 5
- 102000003886 Glycoproteins Human genes 0.000 claims 4
- 108090000288 Glycoproteins Proteins 0.000 claims 4
- 230000002068 genetic effect Effects 0.000 claims 4
- 230000028993 immune response Effects 0.000 claims 4
- 230000002163 immunogen Effects 0.000 claims 4
- 108020004707 nucleic acids Proteins 0.000 claims 4
- 102000039446 nucleic acids Human genes 0.000 claims 4
- 150000007523 nucleic acids Chemical class 0.000 claims 4
- 239000002245 particle Substances 0.000 claims 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims 4
- 230000005867 T cell response Effects 0.000 claims 3
- 239000002299 complementary DNA Substances 0.000 claims 3
- 108091028043 Nucleic acid sequence Proteins 0.000 claims 2
- 241000700605 Viruses Species 0.000 claims 2
- 230000002950 deficient Effects 0.000 claims 2
- 230000005923 long-lasting effect Effects 0.000 claims 2
- 230000007774 longterm Effects 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 230000010076 replication Effects 0.000 claims 2
- 238000001890 transfection Methods 0.000 claims 2
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims 1
- 101001065501 Escherichia phage MS2 Lysis protein Proteins 0.000 claims 1
- 241000585245 Methylophaga aminisulfidivorans Species 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000002672 hepatitis B Diseases 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 238000007918 intramuscular administration Methods 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 238000012423 maintenance Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 230000003472 neutralizing effect Effects 0.000 claims 1
- 230000002265 prevention Effects 0.000 claims 1
- 239000013598 vector Substances 0.000 claims 1
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- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
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- C12N2730/00011—Details
- C12N2730/10011—Hepadnaviridae
- C12N2730/10111—Orthohepadnavirus, e.g. hepatitis B virus
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Claims (16)
1. Zarazni virusni vektor arenavirusa, pri čemu je otvoreni okvir za čitanje arenavirusa uklonjen i zamijenjen nukleotidnom sekvencom odabranom iz skupine koju čine:
a. nukleotidna sekvenca koja kodira HBV HBc protein ili njegov antigenski fragment;
b. nukleotidna sekvenca koja kodira fuziju HBV HBs i HBc proteina ili njihovih antigenskih fragmenata; i
c. nukleotidna sekvenca koja kodira HBV pre-S2/S protein ili njegov antigenski fragment;
pri čemu je virusni vektor sposoban izazvati T-stanični odgovor protiv HBV HBc proteina, fuzije HBV HBs i HBc proteina, HBV pre-S2/S proteina, ili njihovog antigenskog fragmenta.
2. Virusni vektor prema patentnom zahtjevu 1, pri čemu
(i) HBc protein ili njegov antigenski fragment obuhvaća aminokiselinsku sekvencu koja je 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, ili 100% istovjetna aminokiselinskoj sekvenci kodiranoj nukleotidnom sekvencom SEQ ID NO: 2;
(ii) fuzija HBV HBs i HBc proteina ili njihovih antigenskih fragmenata obuhvaća aminokiselinsku sekvencu koja je 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% ili 100% istovjetna aminokiselinskoj sekvenci kodiranoj nukleotidnom sekvencom SEQ ID NO: 3; ili
(iii) pre-S2/S protein ili njegov antigenski fragment obuhvaća aminokiselinsku sekvencu koja je 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89 %, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, ili 100% istovjetna aminokiselinskoj sekvenci kodiranoj nukleotidnom sekvencom SEQ ID NO: 1.
3. Virusni vektor prema patentnom zahtjevu 1, koji obuhvaća najmanje dvije ili najmanje tri od:
a. nukleotidne sekvence koja kodira HBV HBc protein ili njegov antigenski fragment;
b. nukleotidne sekvence koja kodira fuziju HBV HBs i HBc proteina ili njihovih antigenskih fragmenata; i
c. nukleotidne sekvence koja kodira HBV pre-S2/S protein ili njegov antigenski fragment;
izborno pri čemu ekspresija nukleotidnih sekvenci proizvodi antigenski proteinski kompleks koji izaziva veće titre neutralizirajućih protutijela nego ekspresija komponenti proteinskog kompleksa pojedinačno.
4. Virusni vektor prema bilo kojem od patentnih zahtjeva 1 do 3, pri čemu je arenavirus:
(i) virus limfocitnog koriomeningitisa;
(ii) replikacijski defektan i modificiran da sadrži genom sa sposobnošću amplificiranja i izražavanja svoje genetske informacije u zaraženim stanicama, ali bez sposobnosti proizvodnje daljnjih zaraznih čestica potomstva u normalnim, genetičkim nemodificiranim stanicama;
(iii) bi-segmentiran i replikacijski defektan; ili
(iv) trosegmentiran i replikacijski sposoban.
5. Virusni vektor prema bilo kojem od patentnih zahtjeva 1 do 4, pri čemu je otvoreni okvir za čitanje koji kodira glikoprotein (GP) arenavirusa izbrisan ili funkcionalno inaktiviran.
6. Virusni vektor prema bilo kojem od patentnih zahtjeva 1 do 5, pri čemu genomska informacija kodira zarazni virusni vektor arenavirusa koji je dobiven iz virusa limfocitnog koriomeningitisa ili virusa Pichinde, pri čemu je izborno virus limfocitnog koriomeningitisa soj klon 13 virusa limfocitnog koriomeningitisa ili soj MP virusa limfocitnog koriomeningitisa.
7. Virusni vektor prema bilo kojem od patentnih zahtjeva 1 do 6, pri čemu virusni vektor sadrži genomski segment, pri čemu genomski segment obuhvaća:
(i) nukleotidnu sekvencu koja je najmanje 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, ili 100% istovjetna sekvenci nukleotida 1639 do 3315 SEQ ID NO: 11 ili nukleotida 1640 do 3316 SEQ ID NO: 12; ili
(ii) nukleotidnu sekvencu koja kodira produkt ekspresije čija je aminokiselinska sekvenca najmanje 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% ili 100% istovjetna aminokiselinskoj sekvenci kodiranoj nukleotidama 1639 do 3315 SEQ ID NO: 11 ili nukleotidama 1640 do 3316 SEQ ID NO: 12.
8. Virusni vektor prema bilo kojem od patentnih zahtjeva 1 do 7, pri čemu na rast ili zaraznost arenavirusa ne utječe nukleotidna sekvenca.
9. Virusni vektor prema bilo kojem od patentnih zahtjeva 1 do 8, pri čemu je arenavirus virusni vektor zaraznog replikacijski defektnog arenavirusa modificiran da sadrži genom sa sposobnošću amplificiranja i izražavanja svoje genetske informacije u zaraženim stanicama, ali bez sposobnosti proizvodnje daljnjih zaraznih čestica potomstva u normalnim, genetički nemodificiranim stanicama, i pri čemu primjena virusnog vektora arenavirusa subjektu izaziva dugotrajni imunološki odgovor protiv HBV HBc proteina, fuzije HBV HBs i HBc proteina, HBV pre-S2/S proteina ili njihovog antigenskog fragmenta, izborno pri čemu
(i) dugotrajni imunološki odgovor inducira mjerljivi titar protutijela protiv HBV HBc proteina, fuzije HBV HBs i HBc proteina, HBV pre-S2/S proteina ili njegovog antigenskog fragmenta; ili
(ii) dugotrajni imunološki odgovor inducira mjerljivi titar protutijela protiv HBV HBc proteina, fuzije HBV HBs i HBc proteina, HBV pre-S2/S proteina ili njegovog antigenskog fragmenta barem minimalno 4 tjedna;
izborno pri čemu dugotrajni imunološki odgovor povećava titar protutijela protiv HBV HBc proteina, fuzije HBV HBs i HBc proteina, HBV pre-S2/S proteina ili njihovog antigenskog fragmenta za najmanje 100%, za najmanje 200%, za najmanje 300%, za najmanje 400%, za najmanje 500%, ili za najmanje 1000%.
10. Farmaceutski pripravak, imunogeni pripravak ili cjepivo koje sadrži virusni vektor prema bilo kojem od patentnih zahtjeva 1 do 9 i farmaceutski prihvatljiv nosač.
11. Virusni vektor kako je definiran u bilo kojem od patentnih zahtjeva 1 do 9, ili farmaceutski pripravak, imunogeni pripravak, ili cjepivo kako je definirano u patentnom zahtjevu 10, za upotrebu u postupku liječenja ili prevencije infekcije virusom hepatitisa B kod pacijenta.
12. Izolirana nukleinska kiselina, pri čemu nukleinska kiselina sadrži genomski segment arenavirusa, pri čemu je jedan otvoreni okvir za čitanje genomskog segmenta izbrisan ili funkcionalno inaktiviran i pri čemu se genomski segment sastoji se od jedne ili više:
a. nukleotidne sekvence koja kodira HBV HBc protein ili njegov antigenski fragment;
b. nukleotidne sekvence koja kodira fuziju HBV HBs i HBc proteina ili njihovih antigenskih fragmenata; ili
c. nukleotidne sekvence koja kodira HBV pre-S2/S protein ili njegov antigenski fragment;
pri čemu virusni vektor obuhvaća genomski segment arenavirusa sposoban izazvati T-stanični odgovor protiv HBV HBc proteina, fuzije HBV HBs i HBc proteina, HBV pre-S2/S proteina, ili njihovog antigenskog fragmenta, izborno pri čemu je genomski segment kratki segment, pri čemu je otvoreni okvir za čitanje koji kodira glikoprotein (GP) izbrisan.
13. cDNK genomskog segmenta arenavirusa kako je definirano u patentnom zahtjevu 12.
14. In vitro metoda za stvaranje zaraznog replikacijski defektnog virusnog vektora arenavirusa, koja obuhvaća:
a. transfekciju cDNK prema patentnom zahtjevu 13 u stanicu domaćina;
b. održavanje stanice domaćina u uvjetima pogodnim za stvaranje virusa; i
c. sakupljanje zaraznog replikacijski defektnog virusnog vektora arenavirusa;
pri čemu stanica domaćina izražava otvoreni okvir čitanja genomskog segmenta koji je izbrisan ili funkcionalno inaktiviran;
izborno pri čemu metoda dalje uključuje korak a. transfekciju u stanicu domaćina: cDNK drugog genomskog segmenta arenavirusa, nukleinske kiseline koja sadrži otvoreni okvir čitanja (ORF) L proteina i/ili nukleinske kiseline koja sadrži ORF NP-a.
15. Farmaceutski pripravak koji sadrži prvi zarazni virusni vektor replikacijski defektnog arenavirusa modificiranog da sadrži genom sa sposobnošću amplificiranja i izražavanja svoje genetske informacije u zaraženim stanicama, ali bez sposobnosti proizvodnje daljnjih zaraznih čestica potomstva u normalnim, genetički nemodificiranim stanicama, pri čemu se jedan otvoreni okvir za čitanje arenavirusa uklanja i zamjenjuje prvom nukleotidnom sekvencom odabranom iz skupine koja se sastoji od:
a. nukleotidne sekvence koja kodira HBV HBc protein ili njegov antigenski fragment;
b. nukleotidne sekvence koja kodira fuziju HBV HBs i HBc proteina ili njihovih antigenskih fragmenata; i
c. nukleotidne sekvence koja kodira HBV pre-S2/S protein ili njegov antigenski fragment;
i drugi je zarazni virusni vektor, replikacijski defektnog arenavirusa modificiran da sadrži genom sa sposobnošću amplificiranja i izražavanja svoje genetske informacije u zaraženim stanicama, ali bez sposobnosti proizvodnje daljnjih zaraznih čestica potomstva u normalnim, genetički nemodificiranim stanicama, pri čemu se jedan otvoreni okvir za čitanje arenavirusa uklanja i zamjenjuje drugom nukleotidnom sekvencom odabranom iz skupine koja se sastoji od:
a. nukleotidne sekvence koja kodira HBV HBc protein ili njegov antigenski fragment;
b. nukleotidne sekvence koja kodira fuziju HBV HBs i HBc proteina ili njihovih antigenskih fragmenata; i
c. nukleotidne sekvence koja kodira HBV pre-S2/S protein ili njegov antigenski fragment;
pri čemu su prva i druga nukleotidna sekvenca različite; pri čemu su prvi virusni vektor i drugi virusni vektor sposobni izazvati T-stanični odgovor protiv HBV HBc proteina, fuzije HBV HBs i HBc proteina, HBV pre-S2/S proteina ili njihovog antigenskog fragmenta.
16. Virusni vektor prema bilo kojem od patentnih zahtjeva 1 do 9, ili farmaceutski pripravak, imunogeni pripravak ili cjepivo prema patentnom zahtjevu 10, ili farmaceutski pripravak prema patentnom zahtjevu 15, pri čemu je virusni vektor, farmaceutski pripravak, imunogeni pripravak ili cjepivo pogodno za intramuskularnu primjenu ili intravenoznu primjenu.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201562250639P | 2015-11-04 | 2015-11-04 | |
EP16791573.5A EP3371316B1 (en) | 2015-11-04 | 2016-11-03 | Vaccines against hepatitis b virus |
PCT/EP2016/076591 WO2017076988A1 (en) | 2015-11-04 | 2016-11-03 | Vaccines against hepatitis b virus |
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HRP20221474T1 true HRP20221474T1 (hr) | 2023-01-06 |
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