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 delivery polymers. Delivery polymers 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 polymers.
Type:
Grant
Filed:
February 22, 2011
Date of Patent:
November 20, 2012
Assignee:
Arrowhead Madison Inc.
Inventors:
David B. Rozema, David L. Lewis, Darren H. Wakefield
Abstract: The present invention is directed to compounds, compositions, and methods useful for delivering polynucleotides or other cell-impermeable molecules to mammalian cells. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery vehicles. The use of multiple reversible or labile linkages connecting component parts provides for physiologically responsive activity modulation.
Type:
Application
Filed:
February 8, 2012
Publication date:
September 13, 2012
Applicant:
ARROWHEAD MADISON INC.
Inventors:
David B. ROZEMA, Darren H. WAKEFIELD, David L. LEWIS, Jason KLEIN, So WONG, Jon A. WOLFF, James E. HAGSTROM
Abstract: We describe pH-sensitive endosomolytic polymers, delivery particles containing pH-sensitive endosomolytic polymers. The described particles are capable of delivering polynucleotides to cells from the peripheral circulation with subsequent release from endosomes. The endosomolytic polymers are inactive outside the cell but disrupt membranes upon exposure to an acidified endosomal compartment.
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.
Type:
Application
Filed:
December 23, 2011
Publication date:
July 5, 2012
Applicant:
ARROWHEAD MADISON INC.
Inventors:
David 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
Abstract: We describe pH-sensitive endosomolytic polymers, delivery particles containing pH-sensitive endosomolytic polymers. The described particles are capable of delivering polynucleotides to cells from the peripheral circulation with subsequent release from endosomes. The endosomolytic polymers are inactive outside the cell but disrupt membranes upon exposure to an acidified endosomal compartment.
Type:
Grant
Filed:
September 19, 2006
Date of Patent:
July 3, 2012
Assignee:
Arrowhead Madison Inc.
Inventors:
David B. Rozema, Darren H. Wakefield, Jon A. Wolff, James E. Hagstrom, Kirk Ekena
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.
Type:
Application
Filed:
December 15, 2011
Publication date:
June 28, 2012
Applicant:
ARROWHEAD MADISON INC.
Inventors:
David 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 Hoffman, Kerstin Jahn-Hofmann, Peter Mohr, Hans Martin Mueller, Guenther Ott, Ingo Roehl
Abstract: The present invention is directed to compounds, compositions, and methods useful for delivering polynucleotides or other cell-impermeable molecules to mammalian cells. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery vehicles. The use of multiple reversible linkages connecting component parts provides for physiologically responsive activity modulation.
Type:
Grant
Filed:
August 17, 2007
Date of Patent:
March 20, 2012
Assignee:
Arrowhead Madison Inc.
Inventors:
David B. Rozema, James E. Hagstrom, Jason Klein, David L. Lewis, Sean D. Monahan, Darren H. Wakefield, Jon A. Wolff, So Wong
Abstract: The present invention is directed to a class of membrane active polymers useful for cellular delivery of compounds. Conjugation of the described membrane active polymers to targeting, anti-opsonization, and anti-aggregation agents provides polymers suitable for in vivo delivery. The use of multiple reversible linkages connecting component parts provides for physiologically responsive activity modulation.
Type:
Grant
Filed:
May 19, 2008
Date of Patent:
March 20, 2012
Assignee:
Arrowhead Madison Inc.
Inventors:
Darren H. Wakefield, David B. Rozema, Jon A. Wolff, James E. Hagstrom