Aventis Pharma Deutschland, Gmbh

Antonina Rait

Eugen Uhlmann

Anuschirwan Peyman

David William Will

Esther H Chang

Kathleen F Pirollo

The invention relates to a specific modified oligonucleotide complementary to a section of the human Ha-ras gene and mRNA, and its use to specifically regulate, modulate or inhibit expression of the HA-ras gene, and its use as a pharmaceutical for the treatment of conditions arising from the abnormal expression of the Ha-Ras gene, in particular in combination with chemotherapy and radiotherapy. The modified oligodeoxynucleotide according to the invention has the sequence 5&prime;-TxAxTxTxCxCxGxTxCxAxT-3&prime;-O&mdash;PO &mdash;O&mdash;R (SEQ ID NO:1), wherein X is an internucleotide linkage of type o or s, with the proviso that x is an s linkage at least 4 times and at most 9 times, and o means a phosphodiester internucleoside linkage, s means a phosphorothioate internucleoside linkage, R means a C -C alkyl group, &mdash;(CH &mdash;CH O)n-(CH ) &mdash;CH , or &mdash;CH &mdash;CH(OH)CH O&mdash;(CH ) &mdash;CH wherein n is an integer from 1 to 6, m is an integer from 0 to 20 and q is an integer from 7 to 20 and A is 2&prime;-deoxyadenosine, G is 2&prime;-deoxyguanosine, C is 2&prime;-deoxycytidine and T is thymidine.

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Arlington, VA, United States of America

Antonina Rait