In vivo polynucleotide delivery conjugates having enzyme sensitive linkages

US8426554B2 · kind B2 · utility

Assignee

• Arrowhead Madison, Inc. · US

Inventors

• David B. Rozema · Madison, US
• Darren H. Wakefield · Fitchburg, US
• David L. Lewis · Madison, US
• Jon Wolff · Madison, US
• Andrei V. Blokhin · Fitchburg, US
• Jonathan D. Benson · Stoughton, US
• Jeffrey C. Carlson · Madison, US
• Philipp Hadwiger · Kulmbach, DE
• Eric A. Kitas · Aesch, CH
• Torsten Hoffmann · Weil am Rhein, DE
• Kerstin Jahn-Hoffmann · Neu-Isenburg, DE
• Peter Mohr · Basel, CH
• Hans Martin Mueller · Weilheim, DE
• Guenther Ott · Bayreuth, DE
• Ingo Roehl · Memmelsdorf, DE

Key dates

• Filing date: Dec 23, 2011
• Grant date: Apr 23, 2013
• Expiry date: Dec 23, 2031

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2320/30
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention is directed compositions for delivery of RNA interference (RNAi) polynucleotides to cells in vivo. The compositions comprise amphipathic membrane active polyamines reversibly modified with enzyme cleavable dipeptide-amidobenzyl-carbonate masking agents. Modification masks membrane activity of the polymer while reversibility provides physiological responsiveness. The reversibly modified polyamines (dynamic polyconjugate or DPC) are further covalently linked to an RNAi polynucleotide or co-administered with a targeted RNAi polynucleotide-targeting molecule conjugate.