Computational tool for the early screening of monoclonal antibodies for their viscosities |
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| Authors: | Neeraj J Agrawal Bernhard Helk Sandeep Kumar Neil Mody Hasige A. Sathish Hardeep S. Samra |
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| Affiliation: | 1. 77 Massachusetts Avenue, E19–502b;2. Chemical Engineering;3. Massachusetts Institute of Technology;4. Cambridge, MA 02139, USA;5. Current address: Amgen Inc.;6. 1 Amgen Center Dr., Thousand Oaks, CA 91320, USA;7. Novartis Pharma AG;8. Biologics Technical Development and Manufacturing;9. Werk Klybeck, WKL-681.4.42, CH-4057 Basel, Switzerland;10. Pharmaceutical Research and Development;11. Biotherapeutics Pharmaceutical Sciences;12. Pfizer Inc.;13. 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA;14. Biopharmaceutical Development;15. MedImmune LLC;16. One MedImmune Way, Gaithersburg, MD 20878, USA |
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| Abstract: | Highly concentrated antibody solutions often exhibit high viscosities, which present a number of challenges for antibody-drug development, manufacturing and administration. The antibody sequence is a key determinant for high viscosity of highly concentrated solutions; therefore, a sequence- or structure-based tool that can identify highly viscous antibodies from their sequence would be effective in ensuring that only antibodies with low viscosity progress to the development phase. Here, we present a spatial charge map (SCM) tool that can accurately identify highly viscous antibodies from their sequence alone (using homology modeling to determine the 3-dimensional structures). The SCM tool has been extensively validated at 3 different organizations, and has proved successful in correctly identifying highly viscous antibodies. As a quantitative tool, SCM is amenable to high-throughput automated analysis, and can be effectively implemented during the antibody screening or engineering phase for the selection of low-viscosity antibodies. |
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| Keywords: | antibodies biotherapeutics computer simulation spatial charge map viscosity |
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