Compositions and methods for inhibition of expression of protein C (PROC) genes

US9068184B2 · kind B2 · utility

Assignee

• Alnylam Pharmaceuticals, Inc. · US

Inventors

• Ivanka Toudjarska · Medford, US
• John M. Maraganore · Concord, US
• Brian Bettencourt · Groton, US
• Stuart Milstein · Cambridge, US
• Martin Maier · Cambridge, US
• Klaus Charisse · Acton, US
• Kallanthottathil G. Rajeev · Wayland, US
• Satyanarayana Kuchimanchi · Cambridge, US

Key dates

• Filing date: Jun 21, 2012
• Grant date: Jun 30, 2015
• Expiry date: Jun 21, 2032

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2310/3521
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

The invention relates to double-stranded ribonucleic acid (dsRNA) targeting a PROC gene, and methods of using the dsRNA to inhibit expression of PROC. At least one nucleotide of the dsRNA can be a modified nucleotide, e.g., a 2-0-methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group. Other examples of modified nucleotides include a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxymodified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide. A dsRNA of the invention can include one or more of any of these modified nucleotides.