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At Alphamab Oncology, we have developed the first-in-class platform CRAM (Charge Repulsion induced Antibody Mixture) to produce two or more antibodies in one cell line with one CMC process, which reduces the cost and time as compared to manufacturing the different antibodies separately.

Co-expression of the antibody mixture in a single cell line is key to reducing complexity during development and manufacturing of antibody combination. However, co-transfection of multiple light and heavy chains into cells often leads to production of mismatched, heterodimeric by-products that are inactive. Therefore, the development of co-expression systems that robustly and efficiently produce highly active antibody mixtures is a critical step.

In the CRAM platform, we modified the CH3 domain interface of the Fc region by changing several charge pairs to create electrostatic interactions favoring Fc homodimer formation and disfavoring Fc heterodimer formation. When co-expressed, these modified antibodies with altered charge polarity across the Fc dimer interface favorably formed homodimers that fully preserved the functions of each component, rather than inactive heterodimers whose formation was reduced because of repulsive interactions*

The patents for our CRAM platform have been granted in the US, Japan and China.

Yu J, Wang X, Xu T, et al. A rational approach to enhancing antibody Fc homodimer formation for robust production of antibody mixture in a single cell line. Journal of Biological Chemistry, 2017, 292(43):17885.