Rnase l activators and antisense oligonucleotides effective...

C - Chemistry – Metallurgy – 07 – H

Patent

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Details

C07H 21/00 (2006.01) A61K 31/70 (2006.01) A61K 48/00 (2006.01) C12N 15/11 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2246503

The invention concerns compounds and methods for treating infection with Respiratory Syncytial Virus. The compounds comprise an antisense portion, which is complementary to a normally single stranded portion of the RSV antigenomic strand (the mRNA strand), a linker and an oligonucleotide activator of RNase L, a ubiquitous non-specific RNase. The method comprises forming a complex of an activated RNase L and the antisense molecule. The application teaches methods of determining which portions of the RSV antigenomic strand are normally single-stranded. The application teaches that an antisense oligonucleotide having the sequence of residues 8281-8299 of the RSV genome is particularly useful to practice the invention and provides in vitro results superior to those obtainable with the conventional drug of choice, ribavirin.

La présente invention concerne des composés et procédés permettant de traiter les infections à RSV (virus syncytial respiratoire). Lesdits composés comprennent une partie antisens, qui est complémentaire d'une partie normalement monocaténaire du brin antigénomique du RSV (le brin ARN-messager), une séquence de liaison, et un oligonucléotide activateur de RNase L, une RNase ubiquiste non spécifique. Le procédé consiste à former un complexe à partir d'une RNase L activée et de la molécule antisens. L'invention concerne des procédés permettant de déterminer quelles parties du brin antigénomique du RSV sont normalement monocaténaires. Il est démontré qu'un oligonucléotide doté de la séquence de résidus 8281-8299 du génome RSV s'avère particulièrement utile dans l'application de la présente invention et fournit des résultats in vitro supérieurs à ceux qui sont obtenus au moyen de la substance pharmaceutique classiquement utilisée, la ribavirine.

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