HRP20221474T1 - Cjepiva protiv virusa hepatitisa b - Google Patents

Cjepiva protiv virusa hepatitisa b Download PDF

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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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protein
hbv
nucleotide sequence
viral vector
arenavirus
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Thomas Monath
Katherine Cohen
Vera BAUMGARTL-STRASSER
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Hookipa Biotech Gmbh
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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.
HRP20221474TT 2015-11-04 2016-11-03 Cjepiva protiv virusa hepatitisa b HRP20221474T1 (hr)

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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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JP2022010187A (ja) * 2017-02-03 2022-01-14 株式会社三洋物産 遊技機
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