University of California

The Burnham Institute

Abaron Biosciences, Inc.

Jamey D Marth

Hudson H Freeze

James C Paulson

Prabhjit Kaur Grewal

Lesliey G Ellies

Kazuaki Ohtsubo

Lesley G Ellies

The invention provides compositions and methods for enhancing clearance of coagulation factors {e.g., VWF) and platelets from the blood stream of a patient in need thereof. The methods comprise administering to the patient a therapeutically effective amount of an agent that increases clearance of coagulation factors or platelets. Such an agent can be, for example, a neuraminidase.

Methods of treating coagulopathy

The invention is based on the discovery that the gylcosylation enzyme GnT-4 increases glyocsylation and the stability of glucose transporter (Glut) family members, e.g., by increasing lectin binding. Modulators of GnT-4 activity can therefore be identified and used for the treatment of diabetes or pre-diabetes. In addition, inhibitors of GnT-4 activity can be used for the treatment of cancer.

Regulation of glucose and insulin levels by GnT-4 glycosyltransferase activity

This invention provides methods and kits for use in diagnosing genetically transmitted diseases that are associated with deficiencies in glycosylation of glycoconjugates such as glycoproteins, glycolipids, and proteoglycans. The methods and kits are also useful for monitoring the course of treatment of diseases that are associated with glycosylation disorders.

Diagnosis of human glycosylation disorders

This invention provides compounds and methods for treating inflammation. The compounds modulate the coreoligosaccharide-mediated binding of inflammatory cells, such as neutrophils, to endothelial cells and other myeloid cells. Significantly, the of the invention methods block inflammation without affecting lymphocyte trafficking. In some embodiments, the compounds inhibit the activity of a coreGlcNAc transferase that is involved in synthesizing the coreoligosaccharides.

Use of core 2 G1cNAc transferase inhibitors in treating inflammation

This invention provides methods and compositions for treating and preventing atherosclerosis other undesired blood clotting. The methods for treating and preventing atherosclerosis and related conditions involve administering to a mammal an agent that reduces activity of an ST3Gal IV sialyltransferase, which results in enhanced clearance of von Willebrand Factor (vWF) from the mammal.

Prevention of atherosclerosis and undesired blood clotting by reducing von Willebrand factor

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.

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Goleta, CA, United States of America

Jamey D Marth