公开(公告)号：EP0852491B1

公开(公告)日：2004-08-11

申请号：EP96936052.8

申请日：1996-09-27

申请人： BioMarin Pharmaceutical Inc

发明人： BENNETT, D., Clark ,  CAUCHON, Elizabeth ,  FINK, Dominique ,  GROUIX, Brigette ,  HSIA, Ariane ,  DANAGHER, Pamela ,  ZIMMERMAN, Joseph

IPC分类号： A61K38/47 ,  A61P29/00

CPC分类号： A61K38/51 ,  A61K47/50 ,  C07K2319/00 ,  C12N9/88 ,  Y10S424/81

摘要： 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 sufaces 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.