Modified antisense nucleotides complementary to a section of the human Ha-ras gene

US6723706B2 · kind B2 · utility

Assignee

• Aventis Pharma Deutschland GmbH · DE

Inventors

• Eugen Uhlmann · Königstein, DE
• Anuschirwan Peyman · Kelkheim, DE
• David William Will · Schwalbach, DE
• Esther Chang · Fremont, US
• Kathleen F. Pirollo · Rockville, US
• Antonina Rait · Rockville, US

Key dates

• Filing date: Feb 17, 2000
• Grant date: Apr 20, 2004
• Expiry date: Feb 17, 2020

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2310/3531
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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′-TxAxTxTxCxCxGxTxCxAxT-3′-O—PO2—O—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 C8-C21 alkyl group, —(CH2—CH2O)n-(CH2)m—CH3, or —CH2—CH(OH)CH2O—(CH2)q—CH3 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′-deoxyadenosine, G is 2′-deoxyguanosine, C is 2′-deoxycytidine and T is thymidine.