NOVEL ENZYME FORMULATION FOR TREATMENT OF HYPEROXALURIA

DESCRIPTION (provided by applicant): Design of new efficient drug delivery
systems for proteins is one of the major themes of modern biotechnology and
biopharmaceutical industry. We found that crosslinked enzyme crystals (CLECs)
show stability under low pH, on storage and against proteolysis. These
properties make them ideal for gut lumenal therapy. The patient would swallow a
tablet or liquid suspension of CLEC particles composed of a needed metabolic
enzyme or protein. The CLEC agent would survive the harsh acidic pH and
proteolytic environment of the stomach, and pass into the proximal small
intestine. The CLEC particle would then carry out its therapeutic biochemistry
within the gut lumen while remaining resistant to degradation by endogenous
proteases. In this Phase I study, we propose to develop two types of CLECs:
Oxalyl-CoA decarboxylase for oral lumenal therapy and Oxalate oxidase to be
used in the extracorporeal device/dialysis equipment. The Oxalyl-CoA
decarboxylase-CLEC will perform its action in the duodenum while remaining as
crystalline material or by release of activity by dissolution of the CLEC
particle. This target was chosen to address the problems of current therapies
of hyperoxaluna caused by excessive absorption of oxalate due to the absence of
Oxalobacter formigenes bacterium in the intestine or due to inflammatory bowel
disease. In addition, Oxalate oxidase-CLEC may be used in dialysis equipment or
extracorprealdevices to reduce the oxalate content of blood in patients with
Primary Hyperoxaluria. If successful, these approaches will lead to the
introduction of novel, efficient enzyme therapy for the prevention of Oxalate
Kidney Stones.
PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE