Method for treating systemic bacterial, fungal and protozoan infection

Inventors

Genkin, Dmitry Dmitrievich • Tets, Georgy Viktorovich • Tets, Viktor Veniaminovich

Assignees

CLS Therapeutics Ltd

Abstract

The invention is directed to a treatment of diseases that are accompanied by quantitative and/or qualitative changes of blood extracellular DNA and, more particularly, to a treatment of systemic bacterial, fungal and protozoan infections. The inventive method comprises introducing a treatment agent into a circulating blood system of a patient diagnosed with systemic infection caused by bacteria, fungi or protozoa, wherein said treatment agent destroys extracellular DNA in said blood of said patient and wherein said treatment agent used to destroy said extracellular DNA is a DNase enzyme: said agent being administered in doses and regimens which are sufficient to decrease the average molecular weight of circulating extracellular blood DNA in the blood of said patient; such decrease in the average molecular weight can be measured by gel electrophoresis of extracellular blood DNA fraction from the blood of said patient. A DNase enzyme may be applied in a dose and regimen that provide a DNase DNA hydrolytic activity measured in blood plasma that exceeds 1.5 Kunitz units per 1 ml of blood plasma for more than 12 hours within a period of 24 hours.

Core Innovation

The invention relates to DNase-based therapy for treating a systemic infection in a patient in need thereof, where the systemic infection is associated with changes in qualitative and/or quantitative composition of blood extracellular DNA. The treatment comprises introducing into the blood circulation system of the patient a DNase enzyme in a dose and regimen sufficient to decrease the average molecular weight of the blood extracellular DNA in the blood of the patient as measured by gel electrophoresis.

The infection-associated blood extracellular DNA is reduced by DNase-mediated cleavage, with the reduction being monitored by decrease in the average molecular weight of blood extracellular DNA measured by gel electrophoresis. In several embodiments, the DNase dosing regimen is further defined by DNase hydrolytic activity in blood plasma that exceeds 1.5 Kunitz units per ml for more than 12 hours within 24 hours.

The claims specify systemic infections caused by particular pathogens, including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Streptococcus pneumoniae, Candida albicans, Plasmodium berghei, Aspergillus fumigatus, and Shigella flexneri, as well as urinary tract infection settings, malaria, pulmonary aspergillosis, and odontogenic abscesses or phlegmons. Additional patient and infection context is included, such as autosomal dominant polycystic kidney disease (ADPKD) cyst infection.

Claims Coverage

The independent claims define a DNase-enzyme method for treating systemic infections associated with changes in blood extracellular DNA, using a gel-electrophoresis-based endpoint and, in dependent refinements shown, a blood-plasma DNase hydrolytic activity threshold maintained over a defined time window. Independent claims are directed to specific causative pathogens or specific clinical infection contexts.

Across the independent claims, the core claim coverage is methods of treating systemic infections associated with changes in blood extracellular DNA by introducing a DNase enzyme into the blood circulation in a dose and regimen sufficient to decrease the average molecular weight of blood extracellular DNA as measured by gel electrophoresis. Dependent refinements shown further require DNase hydrolytic activity in blood plasma exceeding 1.5 Kunitz units per ml for more than 12 hours within 24 hours for the DNase dosing regimen, and some claims narrow to particular pathogens or clinical contexts such as urinary tract infection, malaria, pulmonary aspergillosis, and odontogenic abscesses or phlegmons.

Stated Advantages

Documented Applications