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April 01, 2009 (Vol. 29, No. 7)

Firm on Quest to Improve Biomanufacturing

AmProtein Bets that Its Novel Tools Will Change the Way Biomolecules Are Produced

  • GC-Rich Method

    The bioreactors are used to improve the production of biotherapeutics in mammalian cells lines. In the past, bacteria like E. coli served as biological factories. Although yields are high for small biomolecules, it is difficult to manufacture large proteins with the proper structure and functional side groups in bacteria. “The majority of approved, marketed biotherapeutics are presently made in mammalian cells,” says Dr. Hui. CHO and other mammalian cell lines, however, grow slowly and generate low yields of biomolecules.

    Dr. Hui discovered an expression vector series pMH 3-5, that speeds production rates and raises yields in CHO cells close to that of E. coli biomanufacturing. The vector is extremely rich in GC base pairs that appear to open chromatin structures.

    About 99% of the chromatin in eukaryotic cells is condensed, and the vector acts like a chromatin-opening tool that exposes genes to transcription factors, thereby, promoting gene transcription. The GC-rich fragment is inserted at the 5' and/or 3' flanking region of the gene of interest. Once it is transferred to the cell nucleus, “it works so well that you can’t stop it,” explains Dr. Hui. “For example, we have produced generic hyper-glycosylated erythropoietin in CHO cells in 24 hours with the vector.”

    AmProtein researchers have used the vector to express 20 recombinant proteins and antibodies. The system achieves protein-expression levels of 50 to 120 picograms per cell per day for larger proteins like antibodies and 20 to 90 picograms per cell per day for smaller proteins in 96-well plates.

    The discovery of the pMH vector series could speed drug development pipelines and reduce research costs, according to Dr. Hui. The patented expression method offers a common mechanism for accelerating all eukaryotic gene expression. The discovery of the GC-rich gene-expression method coupled with the invention of Current bioreactors “can revolutionize research and development and industrial production in the field of protein-expression technology and regulation,” adds Dr. Hui.

  • Dual-Domain Drugs

    Both technologies are being applied to a pipeline of dual-domain drugs, formed by the union of two biomolecules, with independent effects. The resulting larger molecules codistribute more efficiently into disease sites and simultaneously regulate independent disease pathways.

    In theory, dual-domain drugs are ideal for treating cancer, heart disease, inflammatory conditions, and metabolic disorders. Among the dual-domain drugs in AmProtein’s pipeline are ones designed to treat heart disease and cancer. Early animal studies show that dual-domain drugs are quite effective. 

    AmProtein has patented 20 combinations of dual-domain drugs, locking in a pipeline for the future. It is looking for partners in the U.S. and Europe to codevelop drugs in the pipeline. “We are not a company that puts our feet in just one place,” Joudi comments.

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