Synthetic antisense oligodeoxynucleotides and pharmaceutical...

C - Chemistry – Metallurgy – 07 – H

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C07H 21/00 (2006.01) A61K 31/70 (2006.01) A61K 31/7088 (2006.01) A61K 35/28 (2006.01) A61K 48/00 (2006.01) C12N 5/02 (2006.01) C12N 15/11 (2006.01)

Patent

CA 2118235

The invention relates to synthetic phosphorothioated or partially phosphorothioated oligodeoxynucleotides capable of se-lectively modulating hemopoietic bone marrow cells development. More particularly, the invention relates to synthetic antisense oligodeoxynucleotides directed against a region spanning the AUG initiation codon in human ACHE or 2HS genes, having phos-phorothioate bonds linking between the nucleotide bases; synthetic antisense oligodeoxynucleotides directed against a region spanning the AUG initiation codon in human ACHE gene, 2HS gene or BCHE gene or against a 5'-region in the human CHED (cdc2 homolog) gene, having phosphorothioate bonds linking between the four 3'- terminus nucleotide bases. The invention also relates to pharmaceutical compositions comprising as active ingredient at least one synthetic phosphorothioated or partially phos-phorothioated antisense oligodeoxynucleotides according to the invention in a physiologically acceptable carrier or diluent. The antisense oligodeoxynucleotides of the invention and the pharmaceutical compositions containing them are suitable for inhibiting abnormal hemopoietic cells proliferation, inhibiting abnormal platelet proliferation, increasing stem cell fraction in bone marrow cell cultures, enhancing macrophage production and increasing stem cells counts, reducing immune response of organs to be transplanted, suppressing immune response of a recipient of an allotransplanted organ, and arresting growth of malignant tu-mors.

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