DK2405002T3 - Sammensætninger og fremgangsmåder til oligonukleotidformuleringer - Google Patents

Sammensætninger og fremgangsmåder til oligonukleotidformuleringer Download PDF

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DK2405002T3
DK2405002T3 DK11183857.9T DK11183857T DK2405002T3 DK 2405002 T3 DK2405002 T3 DK 2405002T3 DK 11183857 T DK11183857 T DK 11183857T DK 2405002 T3 DK2405002 T3 DK 2405002T3
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oligonucleotide
dna
artificial sequence
oligonucleotides
immunostimulatory
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Eugen Uhlmann
Joerg Vollmer
Arthur M Krieg
Ulrike Samulowitz
Bernhard Noll
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Adiutide Pharmaceuticals Gmbh
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Claims (15)

1. Sammensætning omfattende en i det væsentlige homogen blanding af duplexdannende oligonukleotider, hvor blandingen af duplexdannende oligo-nukleotider er formuleret i en buffer med lavt saltindhold og omfatter et opløst stof, hvor mindst 50% af de duplexdannende oligonukleotider forekommer i monomer eller dimer form, og hvor de duplexdannende oligonukleotider er immunstimulerende oligonukleotider, omfattende: et 5' TLR-aktiveringsdomæne og mindst to palindromregioner, hvor den ene palindromregion er en 5'-palindromregion på mindst 6 nukleotider i længden og forbundet med en 3'-palindromregion på mindst 8 nukleotider i længden enten direkte eller via en spacer, der er en nukleinsyre med en længde på 1-50 nukleotider eller en ikke-nukleotid spacer, hvor oligonukleotidet omfatter mindst et YpR-dinukleotid, og hvor oligonukleotidet ikke er T*C_G*T*C_G*A*C_G*T*T*C_G*G*C*G*C_G*C*G*C*C*G (SEQ ID NO:335).
2. Sammensætning ifølge krav 1, hvor oligonukleotiderne omfatter mindst et umethyleret CpG-dinukleotid.
3. Sammensætning ifølge krav 1 eller 2, hvor TLR-aktiveringsdomænet er TCG, TTCG, TTTCG, TYpR, TTYpR, TTTYpR, UCG, UUCG, UUUCG, TTT eller TTTT.
4. Sammensætning ifølge et af kravene 1 til 3, hvor TLR-aktiveringsdomænet er inden for 5'-palindromregionen.
5. Sammensætning ifølge et af kravene 1 til 3, hvor TLR-aktiveringsdomænet umiddelbart er 5' til 5'-palindromregionen.
6. Sammensætning ifølge et af kravene 1 til 5, hvor 5'-palindromregionen er mindst 8 nukleotider i længden.
7. Sammensætning ifølge et af kravene 1 til 6, hvor 3'-palindromregionen er mindst 10 nukleotider i længden.
8. Sammensætning ifølge et af kravene 1 til 8, hvor hvert duplexdannnde immunstimulerende oligonukleotid omfatter mindst en duplexdannende sekvens.
9. Sammensætning ifølge krav 8, hvor hvert duplexdannende immunstimulerende oligonukleotid omfatter mindst to duplexdannende sekvenser.
10. Sammensætning ifølge et af kravene 1 til 9, hvor den i det væsentlige homogene blanding omfatter mindst to forskellige duplexdannende immunstimulerende oligonukleotider med forskellige nukleotidsekvenser.
11. Sammensætning ifølge et af kravene 1 til 10, hvor mindst et af de Immunstimulerende oligonukleotider omfatter en 2'-modificeret sukkerrest, fortrinsvis en 2'-0-methyl-modificeret sukkerrest.
12. Sammensætning ifølge et af kravene 1 til 11, hvor det opløste stof er en aminosyre eller en alkohol.
13. Sammensætning ifølge et af kravene 1 til 12 til anvendelse ved behandling af cancer.
14. Fremgangsmåde til fremstilling af en i det væsentlige homogen blanding af duplexdannende immunstimulerende oligonukleotider, omfattende: at identificere duplexdannende immunstimulerende oligonukleotider, at formulere de duplexdannende immunstimulerende oligonukleotider i en buffer med lavt saltindhold og et opløst stof til dannelse af en i det væsentlige homogen blanding af oligonukleotider, hvor de duplexdannende oligonukleotider er immunstimulerende oligonukleotider ifølge et af kravene 1 til 9.
15. I det væsentlige homogen blanding af duplexdannende immunstimulerende oligonukleotider, der kan opnås ved fremgangsmåden ifølge krav 14.
DK11183857.9T 2006-02-15 2007-02-15 Sammensætninger og fremgangsmåder til oligonukleotidformuleringer DK2405002T3 (da)

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US77350506P 2006-02-15 2006-02-15
US85824006P 2006-11-09 2006-11-09
EP07750780.4A EP1991678B2 (en) 2006-02-15 2007-02-15 Compositions and methods for oligonucleotide formulations

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