DK2403951T3 - Tumorselektive e1a- og e1b-adenovirusmutanter - Google Patents

Tumorselektive e1a- og e1b-adenovirusmutanter Download PDF

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DK2403951T3
DK2403951T3 DK10749205.0T DK10749205T DK2403951T3 DK 2403951 T3 DK2403951 T3 DK 2403951T3 DK 10749205 T DK10749205 T DK 10749205T DK 2403951 T3 DK2403951 T3 DK 2403951T3
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expression
cells
pea3
deletion
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Tony Reid
Farah Hedjran
Shantanu Kumar
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Univ California
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Claims (19)

1. Farmaceutisk sammensætning omfattende en farmaceutisk acceptabel excipiens og et rekombinant adenovirus, hvor adenovi russet omfatter en modificeret, regulatorisk E1a-sekvens, hvor mindst ét Pea3-bindingssted, eller en funktionel del deraf, er deleteret, hvor den funktionelle del af det mindst ene Pea3-bindingssted er en del af det bindingssted, der, når det deleteres, reducerer bindingsstedets bindingsaffinitet til Pea3.
2. Farmaceutisk sammensætning ifølge krav 1, hvor mindst ét nukleotid i området fra -305 til -141 bibeholdes.
3. Farmaceutisk sammensætning ifølge krav 1 eller 2, hvor mindst ét af Pea3 II, Pea3 III, Pea3 IV og Pea3 V, eller en funktionel del deraf, er deleteret, eventuelt hvor genstanden udvalgt fra a), b) og c) er deleteret: a) mindst ét af Pea3 II og Pea3 III eller en funktionel del deraf; b) Pea3 II, eller en funktionel del deraf, og Pea3 III eller en funktionel del deraf og c) mindst ét af Pea3 IV og Pea3 V eller en funktionel del deraf.
4. Farmaceutisk sammensætning ifølge ét hvilket som helst af kravene 1-3, hvor Pea3 I, eller en funktionel del deraf, bibeholdes, eventuelt hvor mindst ét E2F-bind ingssted, eller en funktionel del deraf, bibeholdes, hvor den funktionelle del af det mindst ene E2F-bind ingssted er en del af det bindingssted, der, når det deleteres, reducerer bindingsstedets bindingsaffinitet til E2F.
5. Farmaceutisk sammensætning ifølge krav 1, hvor det rekombinante adenovirus omfatter deletion af nukleotider, der befinder sig opstrøms for et E1a- initieringssted, hvor de le teringssteder er udvalgt fra: (a) nukleotid -393 til -304; (b) nukleotid -305 til -255; (c) nukleotid -270 til -240; (d) nukleot id -299 t i I -293; (e) nukleotid -270 til -265 eller (f) nukleotid -299 til -293 og nukleotid -270 til -265.
6. Farmaceutisk sammensætning ifølge ét hvilket som helst af kravene 1 til 5 til anvendelse i cancerbehandling.
7. Farmaceutisk sammensætning til anvendelse ifølge krav 6, hvor den farmaceutiske sammensætning er beregnet til etablering af kontakt med en målcelle.
8. Fremgangsmåde in vitro til selektiv ekspression af et peptid i en målcelle, hvilken fremgangsmåde omfatter etablering af kontakt mellem målcellen og et rekombinant adenovirus, hvor adenovi russet omfatter en modificeret, regulatorisk E1a-sekvens, hvor mindst ét Pea3-bindingssted, eller en funktionel del deraf, er deleteret, hvor den funktionelle del af det mindst ene Pea3-b ind ingssted er en del af det bindingssted, der, når det deleteres, reducerer bindingsstedets bindingsaffinitet til Pea3, forudsat at fremgangsmåden ikke er en fremgangsmåde til behandling af menneskeeller dyrekroppen ved kirurgi eller terapi.
9. Genstand ifølge krav 7 eller 8, hvor det rekombinante virus omfatter en deletionsmutant af den regu lator iske E1a-sekvens operativt bundet til en nukleotidsekvens, der koder for et peptid.
10. Genstand ifølge et hvilket som helst af kravene 7 til 9, hvor målcellen er udvalgt fra en neoplastisk celle og en normal celle.
11. Genstand ifølge et hvilket som helst af de foregående krav, hvor det rekombinante virus selektivt udtrykker en E1a-isoform, hvor sekvensen, der koder for E1a-isoformen er operativt bundet til den modificerede regu latori ske E1a-sekvens.
12. Genstand ifølge krav 11, hvor det rekombinante adenovirus selektivt udtrykker E1a-12S eller E1a13S.
13. Genstand ifølge et hvilket som helst af de foregående krav, hvor det rekombinante adenovirus i alt væsentligt udelukker ekspression af en E1a-isoform, hvor sekvensen, der koder for E1a-isoformen er operativt bundet til den modi f i ce rede, regu latoriske E1a-sekvens.
14. Genstand ifølge krav 13, hvor den udelukkede E1a-isoform er E1a-12S eller E1a-13S.
15. Genstand ifølge et hvilket som helst af de foregående krav, hvor det rekombinante adenovirus endvidere omfatter en dna-sekvens indsat i et E1b-19K-i ndsætn ingssted.
16. Genstand ifølge krav 15, hvor indsætningsstedet befinder sig mellem startstedet for E1b-19K og startstedet for E1b 55K.
17. Genstand ifølge krav 15 eller 16, hvor E1b-19K-indsætningsstedet omfatter en deletion af 202 basepar, der følger efter startstedet for E1b-19K.
18. Genstand ifølge et hvilket som helst af kravene 15 til 17, hvor dna-sekvensen er en sekvens, der koder for en tumornekrosefaktor, eller en funktionel del deraf.
19. Genstand ifølge et hvilket som helst af kravene 15 til 17, hvor dna-sekvensen er en sekvens, der koder for kras, eller en funktionel del deraf.
DK10749205.0T 2009-03-02 2010-03-02 Tumorselektive e1a- og e1b-adenovirusmutanter DK2403951T3 (da)

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EP4123030A1 (en) 2009-03-02 2023-01-25 The Regents of the University of California Tumor-selective e1a and e1b mutants
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