Background: Prolor Biotech, Inc. is a clinical stage public company developing long acting therapeutic proteins utilizing a technology called CTP. The technology involves fusion of the C-terminus peptide of hCG, which is a highly O-glycosylated peptide, to the target protein. Manufacturing process was developed to generate a reproducible highly glycosylated CTP-modified long-acting hGH (MOD-4023), which supports a single weekly injection in GH deficient patients. MOD-4023 is manufactured as a non-viscous liquid formulation.
Objective and hypotheses: Characterization of MOD-4023 drug substance glycosylation profile at different batches.
Methods: MOD-4023 characterization was carried out by applying various acceptable analytical methods including glycosylation profiling including O-glycan/sialic acid content and serine site occupancy.
Results: Glycoprofyling analysis of different batches shows that the major O-glycan structure in MOD-4023 is mono-sialylated core 1 with a comparable site occupancy of the O-glycans in MOD-4023 between different batches. Reproducible high levels at different GMP batches of O-glycan and sialic acid content were obtained. The high glycosylation levels contributes to the significant increased hydrodynamic volume of MOD-4023 as compared to recombinant hGH, which results in the elongated circulating time of MOD-4023.
Conclusion: MOD-4023 manufacturing process is robust, producing a highly O-glycosylated product. Based on these findings and combined with its excellent safety profile and significant prolonged GH activity MOD-4023 has the potential to replace the daily injections of hGH now required for the treatment of GH deficiency with a weekly regimen.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology