Novel immune-escape uricase for treatment of hyperuricemia
Ended Project Grant Awarded Last action
- Award ID
- R43AI174703
- Recipient
-
Abzyme Therapeutics LLC UEI H2MLEFWV36N6
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $299,999
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date
- Originally
- Place of performance
- Pennsylvania, USA
Award details come from USAspending.gov.
Description
- 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.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Original award | $299,999 |
Quick answers
Who received award R43AI174703?
R43AI174703 was awarded to Abzyme Therapeutics LLC by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on May 22, 2023.
How much is award R43AI174703 worth?
$299,999 has been obligated on R43AI174703.
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