Patents Assigned to Arrowhead Madison Inc.
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Patent number: 9481661Abstract: We describe anhydride compounds suitable for physiologically labile modification of amine-containing molecules. The described anhydrides form reversible linkages having desirable kinetics for in vivo delivery of biologically active molecules. Also described are endosomolytic polymers formed by modification of membrane active polyamines with the described anhydrides.Type: GrantFiled: May 31, 2012Date of Patent: November 1, 2016Assignee: Arrowhead Madison, Inc.Inventors: Andrei V Blokhin, David B Rozema, Jonathan D Benson, Jeffrey C Carlson
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Patent number: 9345775Abstract: 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: GrantFiled: March 18, 2015Date of Patent: May 24, 2016Assignee: Arrowhead Madison Inc.Inventors: David L Lewis, David B Rozema, Darren H Wakefield
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Patent number: 9249179Abstract: The present invention is directed compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cell in vivo. The pharmacokinetic modulator improve in vivo targeting compared to the targeting ligand alone. Targeting ligand-pharmacokinetic modulator targeting moiety targeted RNAi polynucleotides can be administered in vivo alone or together with co-targeted delivery polymers.Type: GrantFiled: December 15, 2011Date of Patent: February 2, 2016Assignee: Arrowhead Madison Inc.Inventors: Philipp Hadwiger, Torsten Hoffmann, Eric A. Kitas, Peter Mohr, Ingo Roehl, Linda Valis, David B. Rozema, David L. Lewis, Darren H. Wakefield
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Patent number: 9107957Abstract: 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: GrantFiled: June 25, 2013Date of Patent: August 18, 2015Assignee: Arrowhead Madison Inc.Inventors: David B Rozema, David L Lewis, Darren Wakefield, Eric Kitas, Philipp Hadwiger, Jon Wolff, Ingo Röhl, Peter Mohr, Torsten Hoffmann, Kerstin Jahn-Hofmann, Hans Martin Mueller, Günther Ott, Andrei V Blokhin, Jonathan D Benson, Jeffrey C Carlson
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Patent number: 9089611Abstract: The present invention is directed membrane active poly(vinyl ester) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cells in vivo. RNAi polynucleotides are conjugated to the poly(vinyl ester) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(vinyl ester) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.Type: GrantFiled: December 5, 2014Date of Patent: July 28, 2015Assignee: Arrowhead Madison Inc.Inventors: Darren H Wakefield, Nicholas A Rossi, Dan Sheik
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Patent number: 9011919Abstract: 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: GrantFiled: September 14, 2012Date of Patent: April 21, 2015Assignee: Arrowhead Madison Inc.Inventors: David B. Rozema, David L. Lewis, Darren H. Wakefield, Torsten Hoffmann, Eric Kitas, Peter Mohr, Philipp Hadwiger, Wilma Thuer, Linda Valis
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Publication number: 20150104408Abstract: The present invention is directed membrane active poly(acrylate) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides cells in vivo. RNAi polynucleotides are conjugated to the poly(acrylate) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(acrylate) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.Type: ApplicationFiled: November 25, 2014Publication date: April 16, 2015Applicant: ARROWHEAD MADISON INC.Inventors: Darren H. Wakefield, Nicholas A. Rossi, David B. Rozema, Lauren J. Almeida, Anthony L. Perillo-Nicholas
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Patent number: 8932572Abstract: The present invention is directed membrane active poly(vinyl ester) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cells in vivo. RNAi polynucleotides are conjugated to the poly(vinyl ester) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(vinyl ester) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.Type: GrantFiled: August 23, 2012Date of Patent: January 13, 2015Assignee: Arrowhead Madison Inc.Inventors: Darren H. Wakefield, Nicholas Rossi, Dan Sheik
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Patent number: 8933047Abstract: The present invention is directed membrane active poly(acrylate) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides cells in vivo. RNAi polynucleotides are conjugated to the poly(acrylate) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(acrylate) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.Type: GrantFiled: August 23, 2012Date of Patent: January 13, 2015Assignee: Arrowhead Madison Inc.Inventors: Darren H. Wakefield, David B. Rozema, Nicholas Rossi, Lauren Almeida, Anthony L. Perillo-Nicholas
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Patent number: 8809293Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a Hepatitis B Virus gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by Hepatitis B Virus infection using said pharmaceutical composition; and methods for inhibiting the expression of a Hepatitis B Virus gene in a cell.Type: GrantFiled: June 28, 2012Date of Patent: August 19, 2014Assignee: Arrowhead Madison Inc.Inventors: Daniel Chin, Jochen Deckert, Markus Hossbach, Matthias John
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Patent number: 8802773Abstract: 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: GrantFiled: March 15, 2013Date of Patent: August 12, 2014Assignee: Arrowhead Madison Inc.Inventors: David B Rozema, David L Lewis, Darren H Wakefield, Eric A Kitas, Philipp Hadwiger, Jon A Wolff, Ingo Roehl, Peter Mohr, Torsten Hoffmann, Kerstin Jahn-Hofmann, Hans Martin Mueller, Guenther Ott, Andrei V Blokhin, Jeffrey C Carlson, Jonathan D Benson
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Publication number: 20140128584Abstract: We describe anhydride compounds suitable for physiologically labile modification of amine-containing molecules. The described anhydrides form reversible linkages having desirable kinetics for in vivo delivery of biologically active molecules. Also described are endosomolytic polymers formed by modification of membrane active polyamines with the described anhydrides.Type: ApplicationFiled: May 31, 2012Publication date: May 8, 2014Applicant: ARROWHEAD MADISON INC.Inventors: Andrei V. Blokhin, David B. Rozema, Jonathan D. Benson, Jeffrey C. Carlson
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Patent number: 8658211Abstract: 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: GrantFiled: February 8, 2012Date of Patent: February 25, 2014Assignee: Arrowhead Madison Inc.Inventors: David B. Rozema, Darren H. Wakefield, David L. Lewis, Jason Klein, So Wong, Jon A. Wolff, James E. Hagstrom
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Publication number: 20130317079Abstract: The present invention is directed membrane active poly(acrylate) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides cells in vivo. RNAi polynucleotides are conjugated to the poly(acrylate) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(acrylate) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.Type: ApplicationFiled: August 23, 2012Publication date: November 28, 2013Applicant: ARROWHEAD MADISON INC.Inventors: Darren H. Wakefield, David B. Rozema, Nicholas Rossi, Lauren Almeida, Anthony L. Perillo-Nicholas
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Patent number: 8541548Abstract: The present invention is directed compounds for reversibly modification of biologically active molecules. Described are polyconjugates systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery conjugates. The use of reversible modification provides for physiologically responsive activity modulation.Type: GrantFiled: June 17, 2008Date of Patent: September 24, 2013Assignee: Arrowhead Madison Inc.Inventor: David B. Rozema
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Publication number: 20130245091Abstract: 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: ApplicationFiled: September 14, 2012Publication date: September 19, 2013Applicant: ARROWHEAD MADISON INC.Inventors: David B. Rozema, David L. Lewis, Darren H. Wakefield, Torsten Hoffmann, Eric A. Kitas, Peter Mohr, Philipp Hadwiger, Wilma Thuer, Linda Valis
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Patent number: 8501930Abstract: 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: GrantFiled: December 15, 2011Date of Patent: August 6, 2013Assignee: 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
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Publication number: 20130190484Abstract: 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: ApplicationFiled: March 15, 2013Publication date: July 25, 2013Applicant: ARROWHEAD MADISON INC.Inventors: David Rozema, David Lewis, Darren Wakefield, Eric Kitas, Philipp Hadwiger, Jon Wolff, Ingo Roehl, Peter Mohr, Torsten Hoffmann, Kerstin Jahn-Hofmann, Hans Martin Mueller, Guenther Ott, Andrei Blokhin, Jeffrey Carlson, Jonathan Benson
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Publication number: 20130121954Abstract: The present invention is directed membrane active poly(vinyl ester) polymers and compositions for targeted delivery of RNA interference (RNAi) polynucleotides to cells in vivo. RNAi polynucleotides are conjugated to the poly(vinyl ester) polymers and the polymers are reversibly modified to enable in vivo targeted delivery. Membrane activity of the poly(vinyl ester) provides for movement of the RNAi polynucleotides from outside the cell to inside the cell. Reversible modification provides physiological responsiveness.Type: ApplicationFiled: August 23, 2012Publication date: May 16, 2013Applicant: ARROWHEAD MADISON INC.Inventors: Darren H. Wakefield, Nicholas A. Rossi, Dan Sheik
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Patent number: 8426554Abstract: 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: GrantFiled: December 23, 2011Date of Patent: April 23, 2013Assignee: 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-Hoffmann, Peter Mohr, Hans Martin Mueller, Guenther Ott, Ingo Roehl