Structure-Based Charge Calculations for Predicting Properties and Profiling Antibody Therapeutics

( Mar 16, 2022  )

Sino Biological present a method for modeling antibodies and performing pH-dependent conformational sampling, which can enhance property calculations. Structure-based charge descriptors are evaluated for their predictive performance on recently published antibody pI, viscosity, and clearance data. From this, we devised four rules for therapeutic antibody profiling which address developability issues arising from hydrophobicity and charged-based solution behavior, PK, and the ability to enrich for those that are approved by the U.S. Food and Drug Administration. Differences in strategy for optimizing the solution behavior of human IgG1 antibodies versus the IgG2 and IgG4 isotypes and the impact of pH alterations in formulation are discussed.

Key learnings:
How Octet® BLI works in therapeutic discovery and development, including common challenges and solutions
Adoption of the Octet® BLI in the development of advanced therapeutics such as Bispecific antibodies, Nanobodies and Antibody-drug conjugates
Benefits of using a real-time label free analytical tool such as the Octet® BLI relative to ELISA and SPR
Best practices and protocols to generate high-quality data quickly and easily using the Octet® BLI platform

Key Learnings:
• Methods for generating 3D Antibody Models from 2D protein sequence information
• Computational approaches for assessing the developability of Biotherapeutics
• Application of protein descriptors for biophysical property predictions
• Rules for profiling antibody therapeutics
• Considerations for subclass and isotypes in solution behavior and formulation