In vivo polynucleotide delivery conjugates having enzyme sensitive linkages

US8802773B2 · kind B2 · utility

Assignee

• Arrowhead Madison, Inc. · US

Inventors

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

Key dates

• Filing date: Mar 15, 2013
• Grant date: Aug 12, 2014
• Expiry date: Mar 15, 2033

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.