Modified oligoribonucleotide analogs with enhanced...

C - Chemistry – Metallurgy – 12 – N

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C12N 15/11 (2006.01) A61K 31/7125 (2006.01) A61P 37/04 (2006.01) C07H 21/00 (2006.01)

Patent

CA 2609788

The invention provides immunostimulatory compositions and methods for their use. In particular, the immunostimulatory compositions of the invention include RNA-like polymers that incorporate an immunostimulatory sequence motif and at least one chemical modification to confer improved stability against nuclease degradation and improved activity. Specific modifications involving phosphate linkages, nucleotide analogs, and combinations thereof are provided. Compositions of the invention optionally include an antigen and can be used to stimulate an immune response. Also provided are compositions and methods useful for treating a subject having an infection, a cancer, an allergic condition, or asthma. Modified oligoribonucleotide analogs of the invention are believed to stimulate Toll-like receptors TLR7 and TLR8.

L'invention concerne des compositions immunostimulatoires et des procédés permettant leur utilisation. En particulier, les compositions immunostimulatoires de l'invention comprennent des polymères de type ARN qui incorporent un motif de séquences d'immunostimulation et au moins une modification chimique conférant une stabilité améliorée contre la dégradation des nucléases et une activité améliorée. Des modifications spécifiques impliquant des liaisons phosphate, des analogues de nucléotides et leurs associations sont utilisés. Des compositions de l'invention comprennent éventuellement un antigène et peuvent être utilisés pour stimuler une réponse immunitaire. L'invention concerne également des compositions et des procédés utilisés pour traiter un sujet présentant une infection, un cancer, un état pathologique allergique, ou de l'asthme. Des analogues d'oligoribonucléotides modifiés de l'invention servent à stimuler des récepteurs de type Toll, TLR7 et TLR8.

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