C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/11 (2006.01) A61K 31/712 (2006.01) C07H 21/00 (2006.01) A61P 3/06 (2006.01) A61P 3/10 (2006.01) A61P 9/10 (2006.01) A61P 31/14 (2006.01) A61P 35/00 (2006.01)
Patent
CA 2649045
The invention provides pharmaceutical compositions comprising short single stranded oligonucleotides, of length of between 8 and 26 nucleobases which are complementary to human microRNAs selected from the group consisting of miR19b, miR21, miR122a, miR155 and miR375. The short oligonucleotides are particularly effective at alleviating miRNA repression in vivo. It is found that the incorporation of high affinity nucleotide analogues into the oligonucleotides results in highly effective anti-microRNA molecules which appear to function via the formation of almost irreversible duplexes with the miRNA target, rather than RNA cleavage based mechanisms, such as mechanisms associated with RNaseH or RISC.
L'invention concerne des compositions pharmaceutiques contenant des oligonucléotides monocaténaires courts, d'une longueur comprise entre 8 et 23 nucléobases qui sont complémentaires aux microARN humains choisis parmi le groupe comprenant miR19b, miR21, miR122a, miR155 et miR375. Les oligonucléotides courts sont notamment efficaces pour atténuer la répression ARNmi in vivo. Il a été démontré que l'incorporation d'analogues de nucléotides à affinité élevée dans les oligonucléotides débouche sur des molécules d'anti-microARN très efficaces qui agissent par le biais de la formation de duplexes presque irréversibles avec la cible d'ARNmi, plutôt que de mécanismes basés sur le clivage de l'ARN, tels que des mécanismes liés à RNaseH ou RISC.
Elmen Joacim
Kauppinen Sakari
Kearney Phil
Santaris Pharma A/s
Sim & Mcburney
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