University of Washington

Phaserx, Inc.

Genetic Systems Corporation

Other

Washington Research Foundation

University of Massachusetts

Genevant Sciences Gmbh

Bristol-myers Squibb Compnay

Rohm and Haas Company

The United States of America As Represented by the United States Energy

The Green Cross Corporation

World Health Organization

Genetec Systems Corporation

Allan Sachs Hoffman

Patrick S Stayton

Paul Hickok Johnson

Anthony Convertine

Robert W Overell

Anna S Gall

Craig L Duvall

Charbel Diab

Priyadarsi De

Mary Gallagher Prieve

Danielle Benoit

Niren Murthy

Robert C Nowinski

Amber E E Paschal

Lawrence A Crum

David A Tirrell

Pierre D Mourad

Oliver Press

Tyrone M Porter

Anthony J Convertine

Paul Johnson

Buddy D Ratner

John H Priest

Nobuo Monji

Chantal Lackey Reed

Sean D Monahan

Michael S DeClue

Stephen R Hanson

Raymond L Houghton

Scott M Henry

Guohua Chen

Jr-iuan Lai

Liang C Dong

John Hoffman

Mitsuhiro Ebara

Gerard H Llanos

Wayne Richard Gombotz

Hsing-Yeh Parker

Tsuyoshi Shimoboji

Anilbhai S Patel

Dennis E Schwartz

Tadaaki Inoue

Amber E Paschal

Noah Malmstadt

Thomas A Horbett

Elaine K Thomas

Samarth Kulkarni

Chantal Lackey

Amber Ee Paschal

N S Choi

Yoshiki Hayashi

Janice Bohnert

Bradford C Fowler

David Kiaei

Andrew M Garfinkle

Russell J Mumper

Lisa S Bouchard

Xiangchun Yin

Andrew Garfinkle

Lakeshia J Taite

Jessica Garbern

Paul H Johnson

Robert Overell

Provided herein are micellic assemblies comprising a plurality of copolymers. In certain instauces, micellic assemblies provided herein are pH sensitive particles.

Micellic assemblies

Polymeric compounds having spatially controlled bioconjugation sites are described. Functionalization is achieved by selective &#x3c9;-terminal chain extension of polymer chains by radical polymerization, such as reversible addition-fragmentation chain transfer (RAFT) polymerization.

&#x3c9;-functionalized polymers, junction-functionalized block copolymers, polymer bioconjugates, and radical chain extension polymerization

Described herein are copolymers, and methods of making and utilizing such copolymers. Such copolymers have at least two blocks: a first block that has at least one unit that is hydrophilic at physiologic pH, and a second block that has hydrophobic groups. This second block further has at least one unit with a group that is anionic at about physiologic pH. The described copolymers are disruptive of a cellular membrane, including an extracellular membrane, an intracellular membrane, a vesicle, an organelle, an endosome, a liposome, or a red blood cell. Preferably, in certain instances, the copolymer disrupts the membrane and enters the intracellular environment. In specific examples, the copolymer is endosomolytic.

Diblock copolymers and polynucleotide complexes thereof for delivery into cells

Provided herein are micellic assemblies comprising a plurality of copolymers. In certain instances, micellic assemblies provided herein are pH sensitive particles.

Omega-functionalized polymers, junction-functionalized block copolymers, polymer bioconjugates, and radical chain extension polymerization

Provided herein are multiblock copolymers, as well as micelles and therapeutic compositions thereof.

Multiblock copolymers

Provided herein are monomers incorporating folate or other targeting agent, polymers prepared therefrom, polymers prepared therefrom having a therapeutic agent covalently coupled thereto, as well as micelles and therapeutic compositions thereof.

Targeting monomers and polymers having targeting blocks

A composition for delivering an agent to a cell, comprising a bispecific affinity reagent and a pH-responsive, membrane destabilizing polymer. The bispecific affinity reagent may include a first affinity reagent covalently linked to a second affinity reagent, wherein the first affinity reagent binds to a molecule on the surface of a cell, and the second affinity reagent binds to an intracellular target.

Bispecific intracellular delivery vehicles

Compositions comprising a heterogeneous polymeric micelle and an agent (e.g., a polynucleotide) associated with the micelle are disclosed, together with methods for intracellular delivery of such agent.

Heterogeneous polymeric micelles for intracellular delivery

Provided herein are polymeric carriers suitable for the delivery of polynucleotides (e.g. oligonucleotides) and/or other therapeutic agents into a living cell.

Polymeric carrier

Compositions and methods for transport or release of therapeutic and diagnostic agents or metabolites or other analytes from cells, compartments within cells, or through cell layers or barriers are described. The compositions include a membrane barrier transport enhancing agent and are usually administered in combination with an enhancer and/or exposure to stimuli to effect disruption or altered permeability, transport or release. In a preferred embodiment, the compositions include compounds which disrupt endosomal membranes in response to the low pH in the endosomes but which are relatively inactive toward cell membranes, coupled directly or indirectly to a therapeutic or diagnostic agent. Other disruptive agents can also be used, responsive to stimuli and/or enhancers other than pH, such as light, electrical stimuli, electromagnetic stimuli, ultrasound, temperature, or combinations thereof. The compounds can be coupled by ionic, covalent or H bonds to an agent to be delivered or to a ligand which forms a complex with the agent to be delivered. Agents to be delivered can be therapeutic and/or diagnostic agents. Treatments which enhance delivery such as ultrasound, iontopheresis, and/or electrophoresis can also be used with the disrupting agents.

Enhanced transport using membrane disruptive agents

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Seattle, WA, United States of America

Allan Sachs Hoffman