Ibex Technologies R and D, Inc.

Biomarin Pharmaceutical Inc.

Dominique Fink

D Clark Bennett

Joseph J Zimmermann

Kangfu Gu

Maryse Laliberte

Robert Linhardt

Anna Lydia Tkalec

Pamela Danagher

Brigette Grouix

Joseph F Zimmermann

Elizabeth Cauchon

Ariane Hsia

Heparinase enzymes can be used as a medical treatment to reduce localized inflammatory responses. Treatment of activated endothelium with heparinase inhibits leukocyte rolling, adhesion and extravasation. Most of the heparin and heparan sulfate on endothelial cell surfaces and in basement membranes is degraded by exposure to heparinase. In addition, immobilized chemokines, which are attached to heparin/heparan sulfate on activated endothelium are solubilized by heparinase digestion. Heparinase can be infused into the vascular system to inhibit accumulation of leukocytes in inflamed tissue and decrease damage resulting from localized inflammations. Targeting of heparinase to activated endothelium can be accomplished through localized administration and/or use of genetically engineered heparinase containing endothelium ligand-binding domains.

Use of heparinases to decrease inflammatory response

The present invention describes a method for the production of two highly purified enzymes capable of degrading chondroitin sulfate polysaccharides. A multi-step purification method incorporating cell disruption, cation exchange chromatography, affinity chromatography, hydroxylapatite chromatography, high resolution ion exchange chromatography and size exclusion is outlined. A 77,000.+-.5,000 Dalton protein capable of degrading chondroitin sulfates A and C and a 55,000.+-.2,300 Dalton protein capable of degrading dermatan sulfate were isolated. The genes encoding these enzymes, chondroitinase AC and chondroitinase B, respectively, have been cloned and methods for their use are described.

Chondroitin lyase enzymes

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Montreal, Canada

Dominique Fink