PROTEASE FORMULATION BASED ON CROSSLINKED ENZYME CRYSTAL
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(R)) show stability
under low pH, on storage and against proteolysis. The CLECs can be
prepared in high yield and have high protein load. These properties
make them ideal for gut lumenal therapy where the therapeutic action is
performed within an endolumenal channel without the need for
systemic bioavailability of the therapeutic agent. The patient would
swallow a tablet or liquid suspension of CLEC(R) particles composed
of a needed metabolic enzyme or protein. The CLEC(R) agent would
survive the harsh acidic pH and proteolytic environment of the
stomach, and pass into the proximal small intestine with preservation of
its biochemical activity. The CLEC(R) 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 a Protease-CLEC that will be stable under acidic
condition of the stomach and at elevated temperature (37 degrees C)
and in the presence of proteolytic enzymes. The Protease-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
pancreatic insufficiency using a combination of Protease-CLEC and
Lipase-CLEC (which we already developed). In addition, Protease-
CLEC may also help for the treatment of pain in chronic pancreatitis. If
successful, these approaches will lead to the introduction of novel
efficient protein delivery vehicles.
PROPOSED COMMERCIAL APPLICATIONS:
Currently, there are 10,000-13,000 Chronic Pancreatitis patients in the
US and an additional 20,000 in the rest of the world. In addition, there
are 45,000 CF patients in the US and the rest of the world. The
prototype TheraCLEC-protease along with TheraCLEC-lipase has
enormous commercial potential over the currently available pancreatic
enzyme products as well as for adjuvant therapy in autoimmune and
infectious diseases. The worldwide market is currently $400 million
with $200 million from the US alone.
Small Business Information at Submission:
Principal Investigator:Bhami C. Shenoy
ALTUS BIOLOGICS, INC.
625 PUTNAM AVE CAMBRIDGE, MA 02139
Number of Employees: