Antisense oligonucleotides to suppress eicosanoid formation

C - Chemistry – Metallurgy – 07 – H

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Details

C07H 21/04 (2006.01) A61K 31/70 (2006.01) C12N 15/11 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2179168

The present invention provides new antisense oligonucleotides for the treatment of premature labor, premature rupture of the fetal membranes, premature cervical dilation and effacement, preeclampsia, endometriosis, rheumatoid arthritis, ARDs, and glomerulitis. The drugs are antisense oligonucleotides which attenuate the expression of either the mRNA encoding the cyclooxygenase protein or the mRNA encoding the thromboxane A2 synthase protein. Once the mRNA encoding for cyclooxygenase is inhibited, the production of the cyclooxygenase is inhibited thereby inhibiting the production of the cyclooxygenase products such as prostaglandins and thromboxane. Thus, the antisense oligonucleotides provide novel therapy for the treatment of diseases involving cyclooxygenase products, prostaglandins and thromboxane metabolisms. Such diseases include immunological reproductive, cardiovascular, dermatologic, central nervous system disorders in which the release of cyclooxygenase products effects the genesis and progression of the disease. A second object of the invention is to provide new reagents for the research and study of the diseases involving cyclooxygenase products.

La présente invention se rapporte à de nouveaux oligonucléotides antisens utilisés dans la thérapie concernant l'accouchement prématuré, la rupture prématurée des membranes foetales, la dilatation et l'effacement prématurés du col, la prééclampsie, l'endométriose, la polyarthrite rhumatoïde, la détresse respiratoire de l'adulte et la glomérulite. Les médicaments sont des oligonucléotides antisens qui atténuent l'expression soit de l'ARNm codant la protéine cyclooxygénase, soit de l'ARNm codant la protéine thromboxane A¿2? synthase. Lorsque l'ARNm codant pour la cyclooxygénase a été inhibé, la production de la cyclooxygénase est inhibée, ainsi que les produits associés à la cyclooxygénase, tels que les prostaglandines et le thromboxane. Ainsi, les oligonucléotides antisens permettent d'appliquer une nouvelle thérapie concernant les maladies dans lesquelles interviennent les produits associés à la cyclooxygénase, le métabolisme des prostaglandines et du thromboxane. Ces maladies comprennent les troubles immunologiques, le dérèglement du processus de reproduction, les troubles cardiovasculaires, les affections dermatologiques, les troubles du système nerveux central dans lesquels la libération des produits de la cyclooxygénase agissent sur les causes et la progression de la maladie. Un second objet de l'invention est la production de nouveaux réactifs pour la recherche et l'étude des maladies dans lesquelles interviennent les produits de la cyclooxygénase.

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