Biomolecular Structure and Function Group –                                                                                                                      National Institute of Standards and Technology (NIST)/Institute for Bioscience and Biotechnology Research (IBBR)

Host: Adam Barb

"Identifying Structural Variation in Antibody Therapeutics by Multivariate Analysis of 2D NMR"

The development of advanced techniques for the characterization of the structure of protein therapeutics, including monoclonal antibodies (mAbs), is emerging as a major priority in the pharmaceutical industry.  Proper folding of a protein therapeutic is required for drug function, while misfolding or aggregation can lead to loss of efficacy or cause unintended and potentially life-threatening responses. Techniques for accurate and precise characterization of structure for establishing consistency in drug manufacturing, detecting process-related drug-product variations and establishing comparability of biosimilars to innovator reference products are therefore of great interest to the biopharmaceutical industry and regulators.  

In this talk, I will describe two-dimensional nuclear magnetic resonance (2D-NMR) methods we have used to acquire well-resolved structural ‘fingerprints’ of mAbs (~ 150 kDa) at natural isotopic abundance.  I will also describe how principle component analysis (PCA) can be applied directly to the spectral data matrix to allow spectra from highly similar species to be successfully discriminated, with low limits of detection, which could not be distinguished by visual inspection or simple intensity based statistical approaches.  Lastly, I will show how spectral variation identified between species can provisionally be ascribed to structural differences.

BBMB GRADUATE STUDENTS ARE REQUIRED TO ATTEND! 
PLEASE JOIN US AT 3:45 P.M. IN THE MBB ATRIUM FOR REFRESHMENTS