C - Chemistry – Metallurgy – 12 – N
Patent
C - Chemistry, Metallurgy
12
N
C12N 15/11 (2006.01) A61K 31/70 (2006.01) A61K 31/712 (2006.01) A61K 48/00 (2006.01) C07H 21/00 (2006.01) C07H 21/04 (2006.01)
Patent
CA 2651042
The present disclosure describes short antisense compounds, including such compounds comprising chemically-modified high-affinity monomers 8-16 monomers in length. Certain such short antisense compound are useful for the reduction of target nucleic acids and/or proteins in cells, tissues, and animals with increased potency and improved therapeutic index. Thus, provided herein are short antisense compounds comprising high-affinity nucleotide modifications useful for reducing a target RNA in vivo. Such short antisense compounds are effective at lower doses than previously described antisense compounds, allowing for a reduction in toxicity and cost of treatment. In addition, the described short antisense compounds have greater potential for oral dosing.
La présente invention concerne des composés antisens courts, comprenant des composés qui contiennent des monomères à haute affinité modifiés chimiquement, d'une longueur de 8 à 16 monomères. Certains de ces composés antisens courts sont utiles pour réduire des acides nucléiques et/ou des protéines cibles dans des cellules, des tissus et des animaux avec un pouvoir accru et un indice thérapeutique amélioré. Ainsi, l'invention concerne des composés antisens courts, comprenant des modifications de nucléotides à haute affinité, qui sont utiles pour réduire un ARN cible in vivo. Ces composés antisens courts sont efficaces à des doses inférieures à celles des composés antisens décrits auparavant, ce qui permet de réduire la toxicité ainsi que le coût du traitement. En outre, les composés antisens courts décrits ont un plus grand potentiel pour l'administration par voie orale.
Bhanot Sanjay
Geary Richard S.
Mckay Robert
Monia Brett P.
Seth Punit P.
Isis Pharmaceuticals Inc.
Smart & Biggar
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