Antisense composition and method for treating cancer

A - Human Necessities – 61 – K

Patent

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A61K 31/7088 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2557836

A method and composition for of treating cancer, and in particular, for arresting the progression of a solid or primary cancer to a more invasive, metastatic state, are disclosed. The composition includes a substantially uncharged antisense compound (i) having a nuclease-resistant backbone, (ii) capable of uptake by target cancer cells in the subject, (iii) containing between 10-40 nucleotide bases, and (iv) having a base sequence effective to hybridize to a region of processed or preprocessed human SNAIL RNA transcript. The compound, when administered to the subject, is effective to form within target cancer cells in the subject, a base-paired heteroduplex structure composed of human SNAIL RNA transcript and the oligonucleotide compound, where this structure is characterized by a Tm of dissociation of at least 45 ~C. The compound is administered in an amount sufficient to inhibit SNAIL expression in target cancer cells, thereby to inhibit the progression of the patient~s cancer to a more invasive, metastatic state. Also disclosed are methods for preventing the transdifferentiation of peritoneal mesothelial cells and failure of ultrafiltration in a patient undergoing peritoneal dialysis, by including the compound in the patient dialysis fluid.

La présente invention concerne un traitement anticancéreux et une composition à cet effet, procédant par un arrêt de l'évolution d'un cancer installé ou primaire vers un état plus invasif ou métastatique. La composition comprend un composé antisens sensiblement non chargé (i) possédant une ossature résistant aux nucléases, (ii) capable de captage par des cellules cancéreuse cibles du sujet, (iii) contenant de 10 à 40 bases nucléotides, et (iv) disposant d'une séquence de base capable de s'hybrider sur une région de transcription d'ARN Snail humain traité ou pré-traité. Lorsqu'il est administré au sujet, le composé vient former à l'intérieur des cellules cancéreuses cibles une structure hétéroduplexe à paires de bases composée de transcription d'ARN Snail humain et du composé oligonucléotide, cette structure étant caractérisée par une Tm de dissociation d'au moins 45 ·C. Ce composé s'administre en quantité suffisante pour inhiber l'expression Snail dans les cellules cancéreuses cibles, et dont pour inhiber la progression du cancer du patient à un état plus invasif et métastatique. L'invention concerne également des procédés permettant la prévention de la transdifférentiation de cellules mésothéliales du péritoine et la défaillance de l'ultrafiltration chez un patient en dialyse péritonéale, par une inclusion du composé dans le fluide de dialyse du patient.

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