US 11,814,657 B2
Modified DNase and uses thereof
Lilach Chen Zeltsburg, Nahariya (IL); Ilya Ruderfer, Carmiel (IL); Avidor Shulman, Rakefet (IL); Liat Fux, Kiryat-Motzkin (IL); Yulia Ugortsev, Nesher (IL); Hagit Neta, Haifa (IL); Sivan Gelley, Kfar-Saba (IL); Elad Lavee Laviad, Kfar Neter (IL); and Yoseph Shaaltiel, Timrat (IL)
Assigned to Protalix Ltd., Carmiel (IL)
Filed by Protalix Ltd., Carmiel (IL)
Filed on Dec. 20, 2021, as Appl. No. 17/555,557.
Application 17/555,557 is a continuation of application No. 15/540,264, granted, now 11,225,648, previously published as PCT/IL2016/050003, filed on Jan. 4, 2016.
Claims priority of provisional application 62/247,856, filed on Oct. 29, 2015.
Claims priority of provisional application 62/169,724, filed on Jun. 2, 2015.
Claims priority of provisional application 62/163,497, filed on May 19, 2015.
Claims priority of provisional application 62/099,565, filed on Jan. 4, 2015.
Claims priority of provisional application 62/099,560, filed on Jan. 4, 2015.
Prior Publication US 2022/0106578 A1, Apr. 7, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C12N 9/22 (2006.01); C12N 9/16 (2006.01); A61K 38/46 (2006.01); A61P 43/00 (2006.01); A61P 11/00 (2006.01); A61K 38/00 (2006.01)
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.