Recorded talk: Video
Speaker: John Marino, Nist, USA.
Title: Higher Order Structure Assessment of Formulated Biotherapeutics by NMR
Registration: https://lu-se.zoom.us/meeting/register/u5YodOmvpj0rHtH0jZ7o7s0uv6mZxdkfoguv
Abstract:
Protein therapeutics are a highly successful class of drugs that are currently used to treat a number of serious and life-threatening conditions such as cancer, autoimmune disorders, and infectious diseases including COVID-19. These therapeutics have numerous critical quality attributes (CQA) that must be evaluated to ensure safety and efficacy, including that they must adopt and retain the correct structural fold without forming unintended aggregates. The entirety of structural elements from primary sequence to quaternary interactions is termed by the industry as the ‘higher order structure’ (HOS) of the therapeutic, and the development of analytical techniques for HOS characterization throughout the lifecycle of a protein therapeutic, from development to manufacture, has emerged as a major priority in the pharmaceutical industry. To address this measurement need, I will describe the work our group has done to advance and demonstrate (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy methods that provide high-resolution spectral 'fingerprints' of the HOS of protein therapeutics in formulated drug products at atomic resolution. Using measurements on an IgG1k NIST reference mAb (NISTmAb), and mAbs from biopharma partners, I will show how NMR spectral fingerprints can be quantitatively assessed to reveal and classify variations of HOS, paving the way for NMR characterization of protein therapeutics via chemometrics and machine learning that is both objective and automated.
Bio:
Dr. John P. Marino
Co-Director, Institute for Bioscience and Biotechnology Research (IBBR)
University of Maryland & NIST
Leader, NIST Biomolecular Structure & Function Group
Biomolecular Measurement Division, NIST
Dr. John P. Marino currently serves as Co-Director of the Institute for Bioscience and Biotechnology Research (IBBR), a joint research institute of the University of Maryland and NIST and the Group Leader of the NIST Biomolecular Structure & Function Group at IBBR. He also holds an Adjunct Professor appointment in the Department of Chemistry and Biochemistry and is a member of the Molecular and Cell Biology Program at the University of Maryland. Prior to coming to NIST and the University of Maryland in 1997, Dr. Marino completed an A.B in Chemistry from Princeton University in 1989 and a Ph.D. in Chemistry from Yale University in 1995. He then held an Alexander von Humboldt post-doctoral fellowship for two years at the Goethe Universität in Frankfurt, Germany. Over his career, his research has involved the application of Nuclear Magnetic Resonance (NMR) and other biophysical methods to advance precision measurement of proteins and nucleic acids, with a particular focus on applications to therapeutics and vaccines.