Mirus Bio Corporation

Mirus Corporation

Roche Madison Inc.

Other

Arrowhead Madison, Inc.

Wisconsin Alumni Research Foundation

Vical Incorporated

University of California

Mirns Bio Corporation

Arrowhead Pharmaceuticals, Inc.

Miris Bio Corporation

F. Hoffmann-la Roche Ag

Arrowhead Research Corporation

Jon Asher Wolff

James E Hagstrom

Vladimir G Budker

David B Rozema

Sean D Monahan

Paul Michael Slattum

Vladimir S Trubetskoy

Darren H Wakefield

Philip L Felgner

Dennis A Carson

David L Lewis

Robert Wallace Malone

Hans Herweijer

Gary H Rhodes

So Wong

Julia Hegge

Lisa J Hanson

Jason Klein

Lori Higgs

Kirk Ekena

Alexander V Sokoloff

Peter Mohr

Philipp Hadwiger

Torsten Hoffmann

Eric Argirios Kitas

Andrei V Blokhin

Jeffrey Carlson

Jonathan D Benson

Hans Martin Mueller

Ingo Roehl

Kerstin Jahn-Hofmann

Guenther Ott

David J Duke

Aaron G Loomis

Vladimir P Gurevich

Fred Harrison Gage

Jasodhara Ray

Theodore Friedmann

Michael B Rosenberg

James Ludtke

Stuart J Knechtle

Vladimir M Subbotin

Magdolna G Sebestyén

Jeffery Fritz

Malcolm Schinstine

Michael D Kawaja

Jeffrey C Carlson

David M Neville

Christine I Wooddell

Karen Neder

Jue Wang

Paul Slattum

Laura Juckem

Ingo Röhl

Torsten Hoffman

Kerstin Jahn-Hoffmann

Tatyana Budker, Legal Representative

Larry F Whitesell

Matthew R Wolff

James John Ludtke

Magdolna G Sebestyen

Günther Ott

Andrei Blokhin

Vladimir Trubetskoy

Eric A Kitas

Vladimer S Trubetskoy

James E Hangstrom

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

A bacteriophage T7 display vector for expressing and displaying an exogenous peptide, wherein the display vector comprises a polynucleotide encoding a bacteriophage T7 tail fiber protein p17 in which a hepatocyte-targeting determinant sequence is inactivated, and wherein a cloning site is contained in a coding sequence for the tail fiber protein p17 or in a coding sequence for a capsid protein p10B. Also provided are a host cell containing the display vector as described above, a bacteriophage T7 particle comprising at least one copy of a p17 protein which comprises an exogenous peptide displayed thereon, or at least one copy of a p10 protein with an exogenous peptide displayed thereon, wherein a hepatocyte-targeting determinant sequence on the bacteriophage T7 tail fiber protein p17 is inactivated. The present invention further provides a viral lysate containing assembled bacteriophage T7 particle described above, and a method for determining if a candidate peptide is a liver-targeting peptide, or for screening for liver targeting peptides.

T7 phage peptide display system and uses thereof

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.

Peptide-based in vivo siRNA delivery system

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.

In vivo polynucleotide delivery conjugates having enzyme sensitive linkages

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

Growing community of inventors

Madison, WI, United States of America

Jon Asher Wolff