Antibody-based pharmaceuticals are the leading biologic drug platform (> $75B/year). Despite a wealth of information collected on them, there is still a lack of knowledge on their inter-domain structural distributions, which impedes both formulation optimization and understanding of their interactions with the binding partners. To address this measurement gap, we have developed a new methodology to derive biomolecular structure ensembles from small- and wide-angle scattering data supplemented by distance distribution measurements via a library of tagged proteins bound to an unlabeled and otherwise unmodified target biologic. We have employed the NIST monoclonal antibody (NISTmAb) reference material as our development platform towards a general and extendable technology compatible with any non-isotopically labeled immunoglobulin G class mAb. Integrating SAXS/WAXS data with molecular simulations with the DEER measurements, we enable simultaneous determination of structural distributions and dynamics of mAb-based biologics.
How SAXS/WAXS techniques are advancing structural characterization of antibody-based biologics
The critical role of inter-domain structural distribution in therapeutic antibodies development
Novel methodologies which enable simultaneous determination of structural distributions and
dynamics of monoclonal antibodies based therapeutics