Physical stability of therapeutic antibodies, and predictive approaches to antibody formulation and candidate design

Speaker:

Christopher J. Roberts
Chemical and Biomolecular Engineering, University of Delaware

Abstract:

Therapeutic proteins are among the fastest growing segments of the pharmaceutical industry, and represent most of the current blockbuster medicines on the market. Proteins are commonly manufactured and delivered in liquid solution, and the molecular-scale interactions between proteins and their environment dictate key biophysical properties such as solution viscosity, solubility, and multi-scale aggregation or solution micro-structure. Candidate selection for biopharmaceuticals such has therapeutic antibodies has traditionally focused only on clinical attributes such as target selectivity, in vivo half-life, and other features that may implicitly and inadvertently lead to poor biophysical properties from the perspective of manufacturability and product development. For purposes of selecting therapeutic protein candidates and product formulations, this must be balanced with the need for rapid or high-throughput approaches to allow a large range of candidates to be tested in parallel, as well as to consider both dilute and concentrated protein solutions. Advancements in coarse-grained molecular modeling and algorithms for more rapid/efficient sampling have the potential to make these predictions more routine, while also providing “design rules” that can be implemented without the need for expensive simulations. This seminar focuses on a combination of different levels or scales of molecular modeling, combined with “minimalist” experimental data, and development of design rules based on protein sequence and three-dimensional structures. This includes effects of the product formulation or manufacturing conditions, with an emphasis on antibodies and other anisotropic protein structures.

• 10:30 Refreshments
• 10:45–12:00 Talk