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Novel immune-escape uricase for treatment of hyperuricemia

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43AI174703-01A1
Agency Tracking Number: R43AI174703
Amount: $299,999.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: NIAID
Solicitation Number: PA22-176
Timeline
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-05-22
Award End Date (Contract End Date): 2024-04-30
Small Business Information
321 Jones Boulevard
Pottstown, PA 19464-3468
United States
DUNS: 962964990
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: Yes
Principal Investigator
 HIEP TRAN
 (610) 990-7531
 tran@abzymetx.com
Business Contact
 HIEP TRAN
Phone: (610) 990-7531
Email: trchtran@gmail.com
Research Institution
N/A
Abstract

Abstract. High serum urate levels (hyperuricemia) and subsequent monosodium urate crystal deposition
cause gout, the most common inflammatory arthritis in men and postmenopausal women. Gout affects an
estimated 9.2 million adults in the United States. Hyperuricemia is also a major complication in patients with
tumor lysis syndrome. However, the management of hyperuricemia in gout patients is problematic.
Currently, gout patients are treated with small molecule inhibitor urate-lowering drugs. Gout can progress to
destructive arthropathy, deposition of monosodium urate (MSU) crystals (tophi), and nephropathy if urate-
lowering drugs fail. For those patients, infusion of foreign uricases such as a recombinant fungal uricase
(Raburicase) or recombinant mammalian uricase modified with polyethylene glycol (Pegloticase/Krystexxa) is
indicated to control hyperuricemia and dissolve the MSU crystals. Unfortunately, the immunogenicity of the
administered foreign uricase and the ubiquitous presence of anti-PEG antibodies in the population limit the
therapeutic efficacy of Pegloticase/Krystexxa and prevent repeated treatment. We propose to develop a novel
immune-escape uricase that is covered with a glycan shield and contains immune escape mutations. We have
identified uricase from soil bacteria Terriglobus saanensis with excellent enzyme activity at physiological pH,
and that can be expressed and secreted as an active enzyme in yeast and mammalian cells. Using Abzyme's
maturation, surface display and secretion platform, a selected uricase will be displayed on yeast cell surfaces,
subjected to continuous gene evolution and immune selection pressure. At the end of phase I, it is anticipated
that as many as 2 unique functionally-active immune escape uricase variants with a significant reduction in or
no binding to anti-uricase polyclonal antibodies will be isolated, expressed, purified, and characterized. In
Phase II, the most promising molecules will be evaluated in animal models of induced gout pursuant to the
submission of an IND application for the initiation of clinical trials. The novel uricase will offer a number of
therapeutic advantages, including the facilitation of large-scale production and reduced immunogenicity.

* Information listed above is at the time of submission. *

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