Mirus Bio Corporation

Mirus Corporation

Roche Madison Inc.

Arrowhead Madison, Inc.

Mirns Bio Corporation

Other

Arrowhead Pharmaceuticals, Inc.

F. Hoffmann-la Roche Ag

James E Hagstrom

Jon Asher Wolff

Vladimir G Budker

David B Rozema

Sean D Monahan

Paul Michael Slattum

Vladimir S Trubetskoy

Darren H Wakefield

Julia Hegge

Hans Herweijer

Lisa J Hanson

So Wong

Jason Klein

Kirk Ekena

David L Lewis

Lori Higgs

Aaron G Loomis

Vladimir M Subbotin

Jeffery Fritz

Karen Neder

Paul Slattum

Laura Juckem

Magdolna G Sebestyén

Tatyana Budker, Legal Representative

Mark Noble

Larry F Whitesell

Matthew R Wolff

Andrei Blokhin

Vladimir Trubetskoy

Vladimer S Trubetskoy

The present invention is directed to reversibly inactivated membrane active polymers useful for cellular delivery of compounds. Described are polyconjugate systems that incorporate targeting, anti-opsonization, anti-aggregation, and transfection activities into small biocompatible in vivo delivery conjugates. The use of multiple reversible linkages connecting component parts provides for physiologically responsive activity modulation.

Reversibly masked polymers

A low toxicity, highly efficient transfection composition is described with an amphipathic compound containing at least one imidazole. The composition may be used in the process of transfecting nucleic acids into an animal cell.

Transfection compositions using amphipathic compounds

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.

Polyconjugates for in vivo delivery of polynucleotides

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.

Endosomolytic polymers

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.

Membrane active heteropolymers

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.

Compounds and methods are provided for a single-step covalent attachment of a label to a molecule comprising forming a covalently attachable labeling reagent for alkylating the molecule. Then, combining the covalently attachable labeling reagent with a mixture containing the molecule, under conditions wherein the labeling reagent has reactivity with the molecule thereby forming a covalent bond.

Method for single-step attachment of a label to target molecules

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.

Endosomolytic poly(acrylate) polymers

Endosomolytic poly(vinyl ether) polymers

Described is a process for delivering a biologically active compound to a cell by reversibly linking the compound to a membrane active polymer. In particular, polymer-polynucleotide conjugates are described. Methods for reversibly modifying the polymers to decrease cellular toxicity and improve efficacy are provided.

Reversible attachment of a membrane active polymer to a polynucleotide

An intravenous delivery method is described that enables delivery of polynucleotides to extravascular cells of a mammalian limb. The method involves the injection of polynucleotides into a distal vein of a limb that is transiently occluded. Polynucleotide delivery is facilitated by rapid injection in sufficient volume to enable extravasation of the solution into surrounding tissue.

Intravenous delivery of polynucleotides to cells in mammalian limb

Described is a deliverable composition with low toxicity comprising an amphipathic compound, a polycation, and a siRNA. The composition may be used in the process of delivering a siRNA to an animal cell or more particularly, a mammal cell.

Compositions and processes using siRNA, amphipathic compounds and polycations

Disclosed is a system for providing in vivo delivery of molecules or complexes to extravascular mammalian cells using an intravascular administration route. The molecules or complexes are inserted in an injection solution into a mammalian vasculature. Insertion of the injection solution at an appropriate rate transiently increases the volume of extravascular fluid in the tissue thereby facilitating delivery of the molecule to the cell.

Delivery of molecules and complexes to mammalian cells in vivo

Processes are described for obtaining high levels of gene expression in primates after injection of nucleic acid to the liver via the lumen of the hepatic vein. The described process results in high level of gene expression with transient increases in liver enzymes.

Growing community of inventors

Middleton, WI, United States of America

James E Hagstrom