Alza Corporation

Sequus Pharmaceuticals, Inc.

University of Minnesota

Coopervision International Holding Company, LP

Enzon, Inc.

Liposome Technology, Inc.

Other

Yissum Research Development Company of the Hebrew University of Jerusalem Ltd.

Dynavax Technologies Corporation

Miza Corporation

Intradigm Corporation

Samuel Zalipsky

Francis J Martin

Martin C Woodle

Yechezkel Barenholz

Shi Kun Huang

Theresa M Allen

Alberto Gabizon

Paul S Uster

Herve Bercovier

Radwan Kiwan

Joachim B Kohn

Arthur Back

Durgadas Bolikal

George Barany

Victoria Rogers

Fernando Albericio

Andrew Luk

Danilo D Lasic

Shi-Kun Huang

Wei-Ming Zhang

Jane Chang

Aruna Nathan

Robert L Coffman

Gary S Ott

Steven M Chamow

Stewart D Chipman

Luke S Guo

Bei Jin

Yolanda P Quinn

George Z Zhu

Nuria A Sole

Nuria A Sol E

Josh Gittelman

Alberto A Gabizon

Daniel E Levy

The present disclosure relates to cleavable conjugates (for example, particle-based or antibody-based conjugates) of TLR7/8 agonists (for example, 1H-imidazo[4,5-c]quinoline derivatives) containing a conjugation linker, a cleavable linker, and a self-eliminating linker. The present disclosure also related to methods for preparation of the cleavable conjugates, uses thereof for stimulating an effective immune response, and uses thereof for the treatment of cancer.

Cleavable conjugates of TLR7/8 agonist compounds, methods for preparation, and uses thereof

Contact lenses comprising phosphorylcholine groups release beneficial polyionic or guanidinium-containing agents.

Ophthalmic devices for delivery of beneficial agents

A compound comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-containing ligand through a dithiobenzyl linkage is described.

Releasable linkage and compositions containing same

A conjugate comprised of a hydrophilic polymer covalently yet reversibly linked to a amine-, hydroxy- or carboxyl-containing ligand is described. The resulting conjugate is capable of releasing the parent amine, hydroxy, or carboxyl-containing compound via thiol-mediated cleavage. The system allows for delivery of various amino-, hydroxy-, or carboxy-containing drugs in the form of their thiolytically cleavable macromolecular conjugates.

Polymer-biomolecule conjugates are prepared, generally in a site-specific or -selective manner, by a four-component condensation reaction. The method may be used to prepare conjugates having two polymer molecules attached at a single site on a biomolecule. The conjugates are typically water soluble and have beneficial pharmacological properties, such as reduced immunogenicity and increased circulation time.

Preparation of macromolecular conjugates by four-component condensation reaction

A liposome composition and method for delivery of a nucleic acid in vivo or ex vivo is described. The liposomes in the composition are comprised of (i) a cationic lipid and (ii) a lipid joined to a hydrophilic polymer by a releasable linkage. The liposomes are associated with a nucleic acid for delivery to a cell.

Gene delivery mediated by liposome-DNA complex with cleavable peg surface modification

Methods for administering mitomycin C to a multi-drug resistant cell and for reducing the toxicity of the compound are described. In the methods, mitoymic C is provided in the form of a prodrug conjugate, where the drug is linked to a hydrophobic moiety, such as a lipid, through a cleavable dithiobenzyl linkage. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of mitomycin C in its original form. The linkage is stable under nonreducing conditions. The prodrug conjugate can be incorporated into liposomes for administration in vivo and release of mitomycin C in response to endogenous in vivo reducing conditions or in response to administration of an exogenous reducing agent.

Method for treating multi-drug resistant tumors

Conjugates of a hydrophobic moiety, such as a lipid, linked through a cleavable dithiobenzyl linkage to a therapeutic agent are described. The dithiobenzyl linkage is susceptible to cleavage by mild thiolysis, resulting in release of the therapeutic agent in its original form. The linkage is stable under nonreducing conditions. The conjugate can be incorporated into liposomes for administration in vivo and release of the therapeutic agent in response to endogeneous in vivo reducing conditions or in response to administration of an exogeneous reducing agent.

Conjugate having a cleavable linkage for use in a liposome

A liposome composition comprising small, surface-bound effector molecules is disclosed. The liposomes have a surface layer of hydrophilic polymer chains, for enhanced circulation time in the bloodstream. The effector molecules are attached to the distal ends of the polymer chains. In one embodiment, the effector is polymyxin B, for treatment of septic shock.

Enhanced circulation effector composition and method

Reagents for use in preparing a therapeutic liposome composition sensitized to a target cell are described. The reagents include a liposomal composition composed of pre-formed liposomes having an entrapped therapeutic agent and a plurality of targeting conjugates composed of a lipid, a hydrophilic polymer and a targeting ligand. The therapeutic, target-cell sensitized liposome composition is formed by incubating the liposomal composition with a selected conjugate.

Therapeutic liposome composition and method of preparation

A liposome composition for delivery of a nucleic acid in vivo or ex vivo is described. The liposomes in the composition are comprised of (i) a lipid that is neutral in charge at physiologic pH and positively charged at pH values less than physiologic pH and (ii) a lipid joined to a hydrophilic polymer by a dithiobenzyl linkage. The liposomes are associated with a nucleic acid for delivery to a cell.

Liposome composition for delivery of nucleic acid

Growing community of inventors

Redwood City, CA, United States of America

Samuel Zalipsky