US 8,501,930 B2 · Peptide-based in vivo siRNA delivery system

Peptide-based in vivo siRNA delivery system

AssigneeArrowhead Madison Inc.

InventorsDavid B. Rozema, Darren H. Wakefield, David L. Lewis, Jon A. Wolff, Andrei V. Blokhin, Jonathan D. Benson, Jeffrey C. Carlson, Philipp Hadwiger, Eric A. Kitas, Torsten Hoffmann, Kerstin Jahn-Hofmann, Peter Mohr, Hans Martin Mueller, Guenther Ott, Ingo Roehl

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Abstract

The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to hepatocytes in vivo. Targeted RNAi polynucleotides are administered together with co-targeted melittin delivery peptides. Delivery peptides provide membrane penetration function for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness to the delivery peptides.

Claims18

Dependent claims

A conjugate delivery system composition for delivering an RNA interference polynucleotide to a liver cell in vivo comprising:

RNAi-A and Melittin-(L-Gal)x
wherein,
Melittin is a melittin peptide,
L is physiologically labile reversible linkage wherein cleavage of L-Gal restores an amine on Melittin,
Gal is an Asialoglycoprotein Receptor (ASGPr) ligand,
x is an integer having a value greater than 80% of primary amines of Melittin,
RNAi is an RNA interference polynucleotide, and
A is either a hydrophobic group having at least 20 carbon atoms or a galactose cluster.

5 more elements

Dependencies are inferred from the claim text.

Facts

Application

13/326,433Filed 15 Dec 2011 · us provisional application

Priority

17 Dec 2010

Published

US 2012/0165393 A128 Jun 2012

Granted

6 Aug 2013

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Classification17 codes

A61K 47/549
The modifying agent being an organic compound: sugars, nucleosides, nucleotides or nucleic acids
A61K 47/64
The modifying agent being a protein, peptide or polyamino acid: drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying…
A61K 47/6415
Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is…:…
A61P 1/16
Drugs for disorders of the alimentary tract or the digestive system: for liver or gallbladder disorders, e.g. hepatoprotective agents,…