Materials and methods relating to endothelial cell growth inhibitors
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United States of America Patent
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Mar 7, 2006
Grant Date -
Jun 13, 2002
app pub date -
Sep 5, 2001
filing date -
Sep 5, 2000
priority date (Note) -
Expired
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Abstract
Proteolytic enzymes are involved in generation of a number of endogenous angiogenesis inhibitors and it has been shown that urokinase-activated plasmin can process plasminogen to release an angiogenesis inhibitor, K1-5 (protease-activated kringles 1-5). However, this proteolytic protein (proteolytic K1-5) cannot be secreted (exported) from cells and thus is limited in its application as a therapeutic. The present inventor has now engineered a recombinant protein derived from plasminogen which is folded correctly such that it can be secreted from cells in which it is expressed. The inventor surprisingly found that in order to fold correctly such that it can be secreted, the recombinant protein must comprise a secretory signal peptide and a pre-activation peptide derived from plasminogen.
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