A foundational pillar for ensuring the safety and efficacy of any protein therapeutic resides with the characterization of higher order structure (HOS). Perturbations to the HOS can, at the very least, compromise the biological function of the molecule and elicit harmful responses. HOS characterization, once relegated as a footnote in regulatory guidances, now plays a prominent role, including the push to achieve a “fingerprint-like” similarity through an examination of the ‘totality of the evidence’ in the regulatory pathway for biosimilars. To address this critical need, nuclear magnetic resonance (NMR) spectroscopy provides structural information at atomic resolution. These NMR methods can be applied to various therapeutic modalities below 200 kDa, from small peptides to mAbs and mAb-like molecules, antibody drug conjugates and nucleic acids therapeutics. Further, analysis of NMR spectral fingerprints have seen intensive and rigorous application of chemometric tools, making HOS interpretation palatable for the non-expert user.
Upon completion, participant will be able to understand how 2D-NMR serves as a fingerprint for HOS.
Upon completion, participant will be able to appreciate how versatile the 2D-NMR method is for many therapeutic modalities.
Upon completion, participant will be able to grasp how 2D-NMR automated tools have made it accessible for the non-expert operator.