University of California

The Scripps Research Institute

Cytel Corporation

Other

Amgen Inc.

Neose Technologies, Inc.

Abaron Biosciences, Inc.

James C Paulson

Robert J Bayer

Eryn Ujita-Lee

Matthew MacAuley

Michael Kriegler

Carl F Perez

Mary M Bendig

S Tarran Jones

Brian D Livingston

José W Saldanha

Beverly S Adler

Jeffrey K Browne

Eric Richard Sjoberg

Alma L Burlingame

Jasminder Weinstein

Katalin F Medzihradszky

Karen J Colley

Sorge Kelm

William Gillespie

Xiaohong Wen

Corwin Nycholat

David Nemazee

Margaret J Polley

Michael Nunn

Federico C Gaeta

Robert W Chesnut

Robert M Ratcliffe

Brian Thomas Collins

Reiko F Irie

Yukishige Ito

Jamey D Marth

Weihsu Chen

Norihito Kawasaki

Robert W Chestnut

Mary S Perez

Robert D Pfeifer

Tadashi Tai

Donald L Morton

Shiteng Duan

Leslie D Cahan

Shoufa Han

Matthew Macauley

Weihsu Claire Chen

Compositions and methods are described herein that are useful for treating and inhibiting allergic conditions, including reducing the incidence of mast cell mediated anaphylaxis in subjects. The compositions include a carrier that displays an antigen and a Siglec ligand that binds to a Siglec on a mast cell.

Desensitizing mast cells by co-presentation of antigens with high affinity mast cell siglec ligands

The present invention provides liposomal compositions for inducing immune tolerance. The compounds typically comprise a liposome displaying a specific antigen and also a binding moiety for a sialic acid binding Ig-like lectin (Siglec) expressed on B cells. The invention also provides methods for inducing tolerance to a protein or polypeptide antigen (e.g., a protein antigen) in a subject. The methods involve administering to the subject a pharmaceutical composition thatco-presents both the antigen and a glycan ligand for a Siglec expressed on B lymphocytes.

Compositions and methods for inducing immune tolerance

The present invention provides liposomal compositions for inducing immune tolerance. The compounds typically comprise a liposome displaying a specific antigen and also a binding moiety for a sialic acid binding Ig-like lectin (Siglec)expressed on B cells. The invention also provides methods for inducing tolerance to a protein or polypeptide antigen (e.g., a protein antigen) in a subject. The methods involve administering to the subject a pharmaceutical composition that co-presents both the antigen and a glycan ligand for a Siglec expressed on B lymphocytes.

The present invention provides liposome targeting compounds for targeting cells expressing sialic acid binding Ig-like lectin (Siglec). The liposome compounds typically comprise a binding moiety that is a glycan ligand of the Siglec on the target cell. The liposome compounds also incorporate or encapsulate a biological agent (e.g., an antigen or a therapeutic agent) that can be delivered to the target cell to modulate or kill the target cell. The invention also provides methods of using the liposome targeting compounds for targeted delivery of antigen and for modulating immune cells or immune responses.

Liposome targeting compounds and related uses

The invention relates to high affinity Siglec ligands that are useful for isolating cells that express Siglecs and for delivering agents to cells that express Siglecs. In one embodiment, the invention provides a method for treating cancer in a mammal that involves administering a Siglec ligand of the invention to the mammal, where the Siglec ligand is linked to a therapeutic agent.

High affinity Siglec ligands

This invention provides methods for practical in vitro sialylation of glycoproteins, including recombinantly produced glycoproteins. The methods are useful for large-scale modification of sialylation patterns.

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Practical in vitro sialylation of recombinant glycoproteins

The invention provides methods for inhibiting immune responses by inhibiting the biosynthesis of the sialyl galactosides that are involved in immune responses. In particular, B lymphocyte-mediated immune responses are mediated by interfering with synthesis of &agr;2,6 sialylgalactosides, while T lymphocyte-mediated immune responses are inhibited by blocking synthesis of &agr;2,3 sialylgalactosides. The inhibition is accomplished by, for example, inhibiting the activity of a glycosyltransferase involved in synthesis of the respective sialyl galactoside.

Control of immune responses by modulating activity of glycosyltransferases

The present invention relates to compositions and methods for treating inflammation and other pathological conditions using novel blocking P-selectin antibodies that inhibit adhesion of leukocytes to activated platelets and/or to activated vascular endothelium in vivo. Both murine and humanized antibodies are provided.

Method for detecting the presence of P-selectin

DNA isolates coding for sialyltransferase which contain a conserved region of homology and methods of obtaining such DNA are provided, together with expression systems for recombinant production of sialyltransferase.

Compositions and methods for the identification and synthesis of

Compositions and methods for producing sialyltransferases

Antibodies to P-selectin and their uses

The present invention is directed towards compositions and methods for reducing or controlling inflammation and for treating inflammatory disease processes and other pathological conditions mediated by intercellular adhesion. The compositions of the invention include compounds that selectively bind selectin receptors, the selectin binding activity being mediated by a carbohydrate moiety. The selectin-binding moieties of the invention are derivatives of a sialylated, fucosylated N-acetyllactosamine unit of the Lewis X antigen. Compounds containing a selectin-binding moiety in both monovalent and multivalent forms are included in the invention. The compounds of the invention are provided as pharmaceutical compositions which include, for example, liposomes that carry selectin-binding moieties of the invention. The invention further includes immunoglobulins capable of selectively binding an oligosaccharide ligand that is recognized by a selectin receptor.

Intercellular adhesion mediators

A method for genetically engineering cells to produce soluble and secretable Golgi processing enzymes instead of naturally occurring membrane-bound enzymes. Cells are genetically engineered to express glycosyltransferases which lack both a membrane anchor and a retention signal. The resulting altered enzyme becomes soluble and secretable by the cell without losing its catalytic activity. Secretion of the soluble glycosyltransferase by the cell provides for increased production and simplified recovery of glycosyltransferase.

Method for producing secretable glycosyltransferases and other golgi

A single vessel cyclic synthesis process for preparation of a sialyl.alpha.2.fwdarw.3.beta.galactoside is disclosed. In accordance with this process, a sialyltransferase acceptor is sialylated in an aqueous reaction medium by an .alpha.(2,3)sialyl transferase and CMP-sialic acid to form a sialyl donor substrate and CMP. In the presence of the trans-sialidase of Trypanosoma crusi, that sialyl donor substrate provides a sialyl group for a trans-sialidase acceptor, thereby preparing the sialyl.alpha.2.fwdarw.3.beta.galactoside. The .alpha.(2,3)sialyltransferase acceptor is reformed upon trans-sialidation of the latter acceptor, and the sialyl donor substrate is reformed using the .alpha.(2,3)sialyltransferase and a CMP-sialic acid recycling system that combines CMP with sialic acid that is also present in the vessel. The K.sub.m /V.sub.max value for the .alpha.(2,3)sialyltransferase acceptor is less than one-tenth the value of K.sub.m /V.sub.max of the trans-sialidase acceptor for the .alpha.(2,3)sialyltransferase.

Use of trans-sialidase and sialyltransferase for synthesis of

Growing community of inventors

Del Mar, CA, United States of America

James C Paulson