Validation of Originator Sequences by Antibody Domain Mass Determination and Top-Down Sequencing

摘要

In this work the combined use of mAb domain MW determination at the sub-ppm level and middle-down sequencing (MDS) with high sequence validation percentage -near or at 100 %- were evaluated for their validation performance. In the case of Natalizumab 3 sequence errors were curated by MDS, curation yielded 100 % SVP (90 % SC) and sub-ppm domain MW. In this approach very fast accurate MW determination was used to screen for reference structure aberrations and MDS with very high quality validated/curated the reference sequences.