CPC C12N 9/22 (2013.01) [A61K 38/465 (2013.01); A61P 11/00 (2018.01); A61P 43/00 (2018.01); C12N 9/16 (2013.01); A61K 38/00 (2013.01)] | 19 Claims |
1. A modified DNase I protein comprising an amino acid sequence of a DNase I protein, in which at least five carboxylic acid groups are replaced by amide groups, wherein the modified DNase I protein is characterized by a catalytic efficiency with respect to DNA hydrolytic activity in the absence of actin which is greater than a catalytic efficiency of a non-modified DNase I protein with respect to DNA hydrolytic activity in the absence of actin, wherein the modified DNase I protein differs from said non-modified DNase I protein only in said at least five carboxylic acid groups being replaced by said amide group, and wherein the modified DNase I protein is further characterized by at least one property selected from the group consisting of:
a) a DNA hydrolytic activity in the presence of 5 μg/ml human non-muscle actin which is at least 50% of a DNA hydrolytic activity of the modified DNase I protein in the absence of human non-muscle actin, at a modified DNase I concentration of 45 ng/ml;
b) a DNA hydrolytic activity in the presence of 50 μg/ml human non-muscle actin which is at least 20% of a DNA hydrolytic activity of the modified DNase I protein in the absence of human non-muscle actin, at a DNase I concentration of 45 ng/ml;
c) a DNA hydrolytic activity in the presence of 5 μg/ml human non-muscle actin which is at least 150% of a DNA hydrolytic activity of a non-modified DNase I protein in the presence of 5 μg/ml human non-muscle actin, at a DNase I concentration of 45 ng/ml;
d) a DNA hydrolytic activity in the presence of 50 μg/ml human non-muscle actin which is at least 150% of a DNA hydrolytic activity of a non-modified DNase I protein in the presence of 50 μg/ml human non-muscle actin, at a DNase I concentration of 45 ng/ml; and
e) an IC50 with respect to DNA hydrolytic activity in the presence of human non-muscle actin which is at least twice an IC50 of a non-modified DNase I protein with respect to DNA hydrolytic activity in the presence of human non-muscle actin.
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