PEG has been considered as the golden standard for protein therapeutics for years for the fact that PEG was considered as nonimmunogenic. However, studies have proved that PEG-protein conjugates elicit anti-PEG antibodies even in the first administration. Also, recent studies have shown preexisting anti-PEG antibodies in 42% of normal healthy individuals who have not had any previous administration of PEG-protein conjugates. 2 out of 12 biotherapeutics in the market namely, PEG-asparaginase and PEG-uricase produces immune responses where the phase III clinical trials of peg-uricase produced immune responses in 89% patients which lead to rapid clearance of the drug. This whole scenario has lead us to finding a novel ROMP derived protein-polymer conjugates for therapeutics. Our group has already established functionalized polynorbornene as an effective alternative to the conventional polymers used for protein bioconjugation. In our current work, a series of ROMP derived polynorbornene and poly oxanorbornene block copolymers were synthesized to conjugate to uricase enzyme to study the effect of polymer backbone conformation on the immunogenicity of protein-polymer conjugates. Post-synthetic modification of the backbone was performed to isolate changes in backbone conformation and how they performed with respect to the conformation and immunogenicity. Epoxidation of the backbone is expected to increase the hydrophilicity, improving water-solubility, while maintaining the rigidity of the backbone. In contrast, hydrogenation of the backbone olefins will increase flexibility and will give rise to different polymer conformations. Proteins were conjugated through lysine-mediated graft-to technique and characterization was performed by scattering, gel electrophoresis, and ELISA studies.

Effect of polymer conformation on the immunogenicity of the protein-polymer conjugates

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.