Affiliation:
1. ProAbTech Co., Ltd
2. Gwangju Institute of Science and Technology
Abstract
Abstract
Background: Exogenously providing engineered Uox with enhanced half-life is one of the important urate-lowering treatments for gout. The potential of PAT101, a recombinant human albumin (rHA)-conjugated variant, was evaluated and compared as a novel gout treatment through various in vivo studies with PAT101 and competing drugs.
Methods: PAT101 was produced by site-specific conjugation of rHA and Aspergillus flavus Uox (AfUox-rHA) through clickable non-natural amino acid (frTet) and Inverse electron demand Diels-Alder (IEDDA) reaction. In vivo pharmacokinetics, efficacy tests and in vitro immunogenetic assay were performed after single or multiple doses of PAT101 and its competitors in BALB/c mice, Transgenic (TG) mice, Sprague Dawley (SD) rats and non-human primate (NHP).
Results: The half-life of PAT101 in single dose treated TG mice was more than doubled compared to pegloticase. In SD-rats with 4 weeks repeated administration of rasburicase, only 24% of Uox activity remained, whereas in PAT101, it was maintained by 86%. In the Uox KO model, the survival rate of PAT101 was comparable to that of pegloticase. In addition, human PBMC-based CD4+/CD8+ T-cell activation analysis demonstrated that PAT101 has a lower immune response compared to the original drug, rasburicase.
Conclusion: All results suggest that this rHA conjugated AfUox, PAT101, can be provided as a reliable source of Uox for gout treatment.
Publisher
Research Square Platform LLC
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