Molecular heterogeneity was detected in a recombinant immunoglobulin (IgG1) antibody and attributed to the presence of a protein trisulfide moiety. Trisulfide bond formation, of which the predominant modification site was the bond between the heavy and light chains, has been recently observed in IgGs produced in cell culture.  To minimize heterogeneity and control product quality, an understanding of the impact of cell culture process conditions on trisulfide formation is desirable.  Cell culture parameters were varied in bench scale bioreactor studies to investigate the impact on trisulfide formation.  Trisulfide analysis of the samples from these experiments revealed that the trisulfide content varied considerably from <1% to 39%, despite similar growth and productivity.  In particular, culture duration and feeding strategy were important variables.  As a result of tightly controlling cell culture conditions, antibody with reproducible trisulfide levels can be produced.  Strategies for controlling trisulfide levels in cell culture will also be discussed.

Controlling trisulfide modification in recombinant monoclonal antibody produced in cell culture

243rd National Meeting (2012)

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