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US 7,939,304 B2Granted
Mutant MT-SP1 proteases with altered substrate specificity or activity
AssigneeCatalyst Biosciences, Inc.
InventorsSandra Waugh Ruggles, Jack Nguyen
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Abstract
MT-SP1 mutein proteases with altered specificity for the target molecules they cleave can be used to treat human diseases, such as cancer. Cleaving VEGF or VEGFR at certain substrate sequences with wild-type and mutein MT-SP1 proteases can be used to treat pathologies associated with angiogenesis.
Claims17
A mutein membrane type serine protease 1 (MT-SP1) protease that comprises at least one mutation in a scaffold MT-SP1 polypeptide, whereby the substrate specificity or activity of the mutein MT-SP1 polypeptide is altered compared to the scaffold MT-SP1 polypeptide, wherein:
- the scaffold MT-SP1 polypeptide comprises a sequence of amino acids that is at least 95% identical or is identical to the amino acid sequence of a wild type MT-SP1 whose sequence is set forth in SEQ ID NO:1 or SEQ ID NO:2 or is a species variant of the wild type MT-SP1 of SEQ ID NO:1, or is a catalytically active portion thereof;
- the mutein MT-SP1 comprises a mutation at a position selected from among amino acid positions 41, 146, 151, 169, 170, 172, 173, 175, 176, 177, 178, 179, 181, and 224;
- and
- the numbering is for chymotrypsin.
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