Pro-urokinase mutants

Details Pro-urokinase mutants Pro-urokinase mutants

C - Chemistry, Metallurgy

12

N

C12N 15/58 (2006.01) A61K 38/49 (2006.01) C12N 5/10 (2006.01) C12N 9/72 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2165977

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. The figure depicts the flexible loop (amino acids 297-313), in which a substitution occurs.

L'invention concerne des pro-urokinases (pro-UK) obtenues par mutation qui ont une activité thrombolytique et qui ont la même séquence d'acides aminés que la pro-UK native, mais elles contiennent une mutation diminuant la fibrinogénolyse et l'activation non spécifique du plasminogène par un facteur de 10, par comparaison avec pro-UK native, lorsqu'elles sont administrées à un patient, alors que l'activité de formation de la fibrine et l'activité thrombolytique avec l'activation de la plasmine restent similaires à celles de la pro-UK native. La figure 1 illustre la boucle flexible (acides aminés 297 à 313) dans laquelle une substitution a lieu.

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