Fab Antibody Fragment Titer Improvement

Achieving high-titer expression for complex antibody fragments often stalls due to the limitations of standard microbial platforms. In a recent development effort, a partner’s E. coli system failed to produce the volume required for clinical progression. By pivoting to a systematic screening of 800 unique expression strains at a 96-well scale, researchers identified a specialized host capable of exceeding the 2 g/L economic threshold.

The strategy involved testing 160 plasmid configurations that balanced optimized codons, secretion leaders, and ribosomal binding sites. Scaled to 2L fermentation, the lead strain reached active Fab titers of 4.8 g/L after a 96-hour induction. Analytical validation via intact mass spectrometry and BLI confirmed the quality and activity of the resulting protein.

Access the case study below to see the specific induction conditions and screening workflows used to reach these results.