Pro-urokinase mutants
AssigneeNew England Deaconess Hospital Corporation
InventorsJian-Ning Liu, Victor Gurewich
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Abstract
The invention relates to thrombolytically active pro-urokinase (pro-UK) mutants comprising the amino acid sequence of native pro-UK, but including a mutation which causes the pro-UK mutants to induce less fibrinogenolysis and non-specific plasminogen activation than native pro-UK, to have at least a 10-fold lower intrinsic activity than native pro-UK, and to have substantially the same fibrin promotion and thrombolytic activity after plasmin activation compared to native pro-UK when administered to a patient.
Claims9
A thrombolytically active pro-urokinase (pro-UK) mutant consisting of the amino acid sequence of native pro-UK, except wherein said sequence includes one or more substitution mutations of a new histidine or alanine amino acid for a native amino acid at amino acid locations 299, 300, 301, or 313, or of a new glycine amino acid at amino acid location 306 in the amino acid sequence of native pro-UK, and wherein said mutation causes said pro-UK mutant to induce less fibrinogenolysis and non-specific plasminogen activation than native pro-UK when administered to a patient.
Dependencies are inferred from the claim text.