Mirus Bio Corporation

Arrowhead Pharmaceuticals, Inc.

Arrowhead Madison, Inc.

Roche Madison Inc.

Mirns Bio Corporation

Kirk Ekena

Jon Asher Wolff

David B Rozema

James E Hagstrom

Darren H Wakefield

Vladimir G Budker

Sean D Monahan

Lisa Nader

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

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

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

Compositions and methods for delivery of proteins and peptides to mammalian cells in vitro are described. Specifically, polypeptide-surfactant complexes formed from noncovalent hydrophobation of polypeptides and reversible hydrophobic modification of polypeptides are described. The compositions can be used to delivery positively charged, negatively charged and charge neutral polypeptides to cells.

Protein and peptide delivery to mammalian cells in vitro

An process for the reversible modification of an amine-containing compound is described. Modification of the compound can be used to facilitate delivery of molecules to cells in vitro and in vivo or to alter interactions or activities the compounds. The described modifiers can also be utilized as cross-linkers.

Reversible modification of amine-containing compounds

An process for the reversible modification of membrane interaction of a compound is described. Modification of membrane interaction can be used to facilitate delivery of molecules to cells in vitro and in vivo. The described modifiers, which are used to reversibly inactivate the membrane active compounds, can also be utilized as cross-linkers or to reverse the charge of a molecule.

Growing community of inventors

Fitchburg, WI, United States of America

Kirk Ekena