Drug – bio-affecting and body treating compositions – Enzyme or coenzyme containing – Transferases
Patent
1994-07-08
1999-12-07
Hobbs, Lisa J.
Drug, bio-affecting and body treating compositions
Enzyme or coenzyme containing
Transferases
424 9461, 435200, 435201, 435232, 514 2, 514 8, 530825, 536 232, 536 234, A61K 3851, A61K 3847, C12N 988, C12N 926
Patent
active
059978635
ABSTRACT:
Glycosaminoglycans, including heparinases 1, 2 and 3 as well as chondroitinases AC and B from the Gram negative bacteria Flavobacterium heparinum, can be used either separately or in combination to manipulate cell proliferation. In one embodiment, heparinases are administered to degrade heparan sulfate components of the extracellular matrix, thereby allowing the heparin binding growth factors which are stored in the extracellular matrix to migrate to adjacent cells. The mobility of chemoattractant agents, growth factors and cells also can be increased by treating tissues with glycosaminoglycan degrading enzymes, both chondroitinases and heparinases. The enzymatic removal of chondroitin sulfates from cell surfaces effectively increases the availability of growth factor receptors on the cell's surface. Selectively removing heparan sulfate from cell surfaces while leaving the extracellular matrix intact, conversely, inhibits cell proliferation by down regulating the cell's response to growth factors. This is achieved by targeting heparin or heparan sulfate degrading activities to the cell surface. Targeting the heparin degrading activity can be achieved by genetically engineering a ligand binding functionality into the heparinase proteins, or by physically controlling the localized enzyme concentration through the method of administration.
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Sasisek
Bennett Clark
Broughton Richard
Danagher Pamela
Vlodavsky Israel
Zimmermann Joseph
Hobbs Lisa J.
Ibex Technologies R and D, Inc.
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