title: Computational tool for the early screening of monoclonal antibodies for their viscosities.
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.
authors.affiliation: a 77 Massachusetts Avenue, E19-502b; Chemical Engineering; Massachusetts Institute of Technology ; Cambridge , MA 02139 , USA.|f Current address: Amgen Inc.; 1 Amgen Center Dr. , Thousand Oaks , CA 91320 , USA.
authors.forename: Neeraj J
authors.initials: NJ
authors.lastname: Agrawal
authors.affiliation: b Novartis Pharma AG; Biologics Technical Development and Manufacturing ; Werk Klybeck , WKL-681.4.42, CH-4057 Basel , Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Helk
authors.affiliation: c Pharmaceutical Research and Development; Biotherapeutics Pharmaceutical Sciences; Pfizer Inc. ; 700 Chesterfield Parkway West, Chesterfield , MO 63017 , USA.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kumar
authors.affiliation: d Biopharmaceutical Development; MedImmune LLC ; One MedImmune Way, Gaithersburg , MD 20878 , USA.
authors.forename: Neil
authors.initials: N
authors.lastname: Mody
authors.affiliation: d Biopharmaceutical Development; MedImmune LLC ; One MedImmune Way, Gaithersburg , MD 20878 , USA.
authors.forename: Hasige A
authors.initials: HA
authors.lastname: Sathish
authors.affiliation: d Biopharmaceutical Development; MedImmune LLC ; One MedImmune Way, Gaithersburg , MD 20878 , USA.
authors.forename: Hardeep S
authors.initials: HS
authors.lastname: Samra
authors.affiliation: c Pharmaceutical Research and Development; Biotherapeutics Pharmaceutical Sciences; Pfizer Inc. ; 700 Chesterfield Parkway West, Chesterfield , MO 63017 , USA.
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Buck
authors.affiliation: e Pharmaceutical Research and Development; Biotherapeutics Pharmaceutical Sciences; Pfizer Inc. ; 1 Burtt Road, Andover , MA 01810 , USA.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: a 77 Massachusetts Avenue, E19-502b; Chemical Engineering; Massachusetts Institute of Technology ; Cambridge , MA 02139 , USA.
authors.forename: Bernhardt L
authors.initials: BL
authors.lastname: Trout
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D012984:Software; D014783:Viscosity
chemical_list: D000911:Antibodies, Monoclonal
keywords: antibodies; biotherapeutics; computer simulation; spatial charge map; viscosity