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Highland Games: A benchmarking exercise in predicting biophysical and drug properties of monoclonal antibodies from DNA sequences

Published

Author(s)

John E. Schiel, Coffman Jon, Bruno Marques, Griesbach Jan, Ambrose Williams, Gisela Ferreira, Rushd Khalaf, David Roush, Charles Haynes

Abstract

Biopharmaceutical product and process development does not yet take advantage of predictive computational modeling to nearly the degree seen in industries based on smaller molecules. To assess and advance progress in this area, spirited coopetition was successfully used to motivate industrial scientists to develop, share, and compare data and methods which would normally have remained confidential. The first “Highland Games” competition was held in conjunction with the October 2018 Recovery of Biological Products Conference in Ashville, NC, USA. The goal of Highland Games is benchmarking and assessment of the ability to predict development-related properties of antibodies from their amino acid sequences alone. Predictions included purification-influencing properties such as isoelectric point and Protein A elution pH, and biophysical properties such as stability and viscosity at very high concentrations. Essential contributions were made by a large variety of individuals, including companies which consented to provide antibody amino acid sequences and test materials, volunteers who undertook the preparation and experimental characterization of these materials, and prediction teams who attempted to predict antibody properties from sequence alone. Best practices were identified and shared, and areas in which the community excels at making predictions were identified, as well as areas presenting opportunities for considerable improvement. Predictions of isoelectric point and Protein A elution pH were notably good with the all- prediction average error at 0.2 and 1.6 pH unit, respectively, while predictions of some other properties were notably less good. This manuscript presents the events, methods, and results of the competition, and can serve as a tutorial and as a reference for in-house benchmarking by others. Organizations vary in their policies concerning disclosure of methods, but most managements were very cooperative with the Highland Games exercise, and c
Citation
mAbs

Keywords

chromatography, aggregation, purification, molecular simulation, developability, QSAR
Created April 7, 2020, Updated April 28, 2020