Session: SAT 632-648-Pediatric Growth Case Reports
Poster Board SAT-647
Prolor Biotech Inc. develops long acting therapeutic proteins utilizing a technology called CTP which involves fusion of the C terminus peptide of β-hCG, a highly O-glycosylated peptide, to the target protein. To date, most available recombinant human growth hormone (hGH), a non-glycosylated protein, is expressed in E-coli. A robust manufacturing process was developed in which a long acting CTP-hGH (MOD-4023) with proper O-glycosylation, was expressed, recovered and purified from CHO cells and in high yields.
The objective was to develop a highly-producing upstream manufacturing process of MOD-4023 by r-DNA technology using CHO cells in a chemically defined medium, followed by a robust and scalable downstream process for isolating the highly glycosylated protein.
The cDNA of MOD-4023 was transfected into CHO cells and stable clones were generated. Highest producing clones were amplified with increasing concentrations of Methotrexate and the final clone was selected for further development. Comprehensive process development program included media and feed screening in Tubespin® and instrumental bioreactors followed by process parameters optimization. The downstream process was developed to purify the highly glycosylated MOD-4023 in high yield and effectively remove process impurities.
A robust manufacturing fed-batch process of MOD-4023 was developed in CHO cells with a high productivity and yield. Producing cells are grown in commercial chemically defined media including a commercially animal free feeding step. Purification process is based on a series of anion, - cation and mixed-mode ion exchange and hydrophobic interaction chromatography steps, accompanied by a virus-inactivation and nanofiltration. The downstream process selectively purifies the highly-glycosylated MOD-4023 and exhibits high capacity for removal of process related impurities including viral removal capacity, DNA and host cell proteins.
A Large-scale fed-batch manufacturing process for MOD-4023 suitable for supporting clinical development and commercial manufacturing was developed with high productivity, yield, product quality and very low residual impurities in compliance with regulatory guidelines. The final high yield makes it comparable to standard hGH manufacturing processes in E-Coli with respect to cost of goods.
Nothing to Disclose: OH, LM, YF, RG, EF
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