Background: OPKO Biologics is a clinical-stage public company developing long-acting therapeutic proteins utilizing CTP technology. The technology involves fusion of the C-terminal peptide of human chorionic gonadotropin (hCG), which is highly O-glycosylated, to the target protein. CTP enabled the production of a long-acting human growth hormone (hGH) (MOD-4023), which supports a single weekly injection in growth hormone-deficient patients. MOD-4023 is manufactured as a non-viscous liquid formulation.
Objective: The objective of the study was to develop a highly O-glycosylated drug product with respect to protein quality attributes, process reproducibility, and batch-to-batch consistency.
Methods: The consistency of MOD-4023 glycosylation was tested by applying various analytical methods, including O-glycan and sialic acid analysis by HPLC, capillary zone electrophoresis (CZE), and isoelectric focusing (IEF). MOD-4023 potency was assessed in vitro by a cell-based assay (CBA), utilizing cells that stably express the human growth hormone receptor (GHR).
Results: Similar O-glycan and sialic acid contents were obtained in different of MOD-4023 batches, supporting the consistency of the drug substance glycosylation profile for each batch. Comparable results for different batches were also obtained using both CZE and IEF analysis. Several batches of MOD-4023 had shown similar levels of binding and activation of the human GHR.
Conclusion: A robust manufacturing process was developed for the production of MOD-4023 DS, producing a highly reproducible O-glycosylated product.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology