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 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
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: A disposable dog waste handling device includes a framework; and a flexible bag, attached to the framework, having a portion capable of lying flat under the dog to capture feces eliminated from the dog, the bag adapted to retain the feces when the device is lifted. The device may be operated by a user using one hand so that, when the user lifts an end of the framework, the bag retains the feces and the user does not feel the eliminated feces. The framework includes a strip of flexible material that forms a loop, and the bag may not detach from the material. The entire device is then thrown away.
Abstract: The present invention relates to compositions and methods for increasing long term expression in vitro and in vivo, comprising sequences and gene expression cassettes that increase expression of genes to which they are operably linked.
Abstract: The present invention is directed to membrane active polymers useful for cellular delivery of compounds. 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:
Grant
Filed:
June 17, 2008
Date of Patent:
September 13, 2011
Assignee:
Roche Madison Inc.
Inventors:
Darren H. Wakefield, David B. Rozema, Sean D. Monahan, Lori Higgs, Jon A. Wolff, James E. Hagstrom
Abstract: The present invention is directed to membrane active polymers useful for cellular delivery of compounds. 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:
Grant
Filed:
June 17, 2008
Date of Patent:
August 30, 2011
Assignee:
Roche Madison Inc.
Inventors:
David B. Rozema, Darren H. Wakefield, Sean D. Monahan, Lori Higgs, Jon A. Wolff, James E. Hagstrom
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:
Application
Filed:
February 22, 2011
Publication date:
August 25, 2011
Applicant:
ROCHE MADISON INC.
Inventors:
David B. Rozema, David L. Lewis, Darren H. Wakefield, Torsten Hoffmann, Erik Kitas, Peter Mohr, Philipp Hadwiger, Wilma Thuer, Linda Valis
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:
July 26, 2011
Assignee:
Roche Madison Inc.
Inventors:
Sean D. Monahan, Darren H. Wakefield, David B. Rozema, Lori Higgs, Jon A. Wolff, James E. Hagstrom
Abstract: A fluidised bed filter comprises a drying pan, and a filter assembly having a membrane over the pan, and a plurality of openings in the membrane. A filter bag is secured to each aperture by means of a clamping ring attached to the rim of the respective aperture, and cooperating with a clamping band within the cuff of the bag. The material of the bag is clamped between the ring and the band. The ring is covered in a cloth strip, which is folded over to produce a flap, which is stitched between the layers of a double fabric forming the membrane. The band is retained in a tunnel formed by a fold in a double fabric forming the filter bag by stitching.
Abstract: A non-invasive and non-destructive apparatus and testing method for analytes in sealed containers are provided, which are especially useful for identifying bottles of wine that are contaminated with 2,4,6-trichloroanisole (TCA) without destroying the value of uncontaminated wine by opening the bottles or marring the containers or labeling. The apparatus and method are applicable to non-destructively testing any “stream-of-commerce” containers such as shampoo bottles, aerosol containers, toothpaste tubes, and soft drink cans, and other such containers for the presence of contaminants, explosives, poisons, drugs, and other dangerous or illegal materials. The method provided is orders of magnitude more sensitive than other methods, and can detect the presence of diffused substances at the nanogram per liter (parts-per-billion) level.
Abstract: A filter element comprises a pleated filter (10), one end of which is received in an end cap (11), which is made up of a unitary moulding comprising an end part (21) of a harder plastics material, and a lower part (22) of a softer plastics material, the plastics being compatible or of the same composition, differing only in hardness. A groove (24) engages with a support plate (14), the groove being formed in the softer material abutting the harder material so that the latter forms one face of the groove. A perforated support sleeve (29) can be inserted by dropping into the filter, and an end cap (12) at the other end of the filter either closes the end or is adapted for connection to a further similar filter.