The structure of N-linked oligosaccharides attached to the IgG heavy chain constant region (Fc) is an important consideration due to the potential impact on pharmacokinetic profile and antibody effector functions including antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). The N-linked carbohydrates found on recombinant IgGs (rIgGs) produced in murine myeloma cells differ significantly from those produced in Chinese Hamster Ovary (CHO) cells, since they may contain monosaccacharide components such as alpha-galactose and N-glycolylneuraminic acid.  Additionally, differences in oligosaccharide profiles not intrinsic to host cell line differences, such as the level of hybrid glycans or degree of terminal b-galactosylation, may also be present when comparing rIgGs produced from murine myeloma cells with those produced in CHO. Understanding the criticality of these glycans to biological activity is an essential component of biosimilar development, particularly when the use of alternative host cell systems is under consideration. In this study, we describe a series of glycan remodeling studies performed to evaluate the biological relevance of glycan structures typically found in murine myeloma cells.  This study underscores the importance of understanding attribute criticality which in concert with tightly controlled rIgG manufacturing processes and a comprehensive structural and functional analysis of glycan structures, using state of the art analytical tools, highlights the potential of pursuing a host cell system that differs from that used for the innovator product.  This approach can enable the development of a biosimilar that is functionally highly similar to the innovator product.

Understanding attribute criticality for host cell system selection for biosimilar development

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.