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In Molecular pharmaceutics ; h5-index 60.0

Predicting the solution viscosity of monoclonal antibody (mAb) drug products remains as one of the main challenges in antibody drug design, manufacturing, and delivery. In this work, the concentration-dependent solution viscosity of 27 FDA-approved mAbs was measured at pH 6.0 in 10 mM histidine-HCl. Six mAbs exhibited high viscosity (>30 cP) in solutions at 150 mg/mL mAb concentration. Combining molecular modeling and machine learning feature selection, we found that the net charge in the mAbs and the amino acid composition in the Fv region are key features which govern the viscosity behavior. For mAbs whose behavior was not dominated by charge effects, we observed that high viscosity is correlated with more hydrophilic and fewer hydrophobic residues in the Fv region. A predictive model based on the net charges of mAbs and a high viscosity index is presented as a fast screening tool for classifying low- and high-viscosity mAbs.

Lai Pin-Kuang, Fernando Amendra, Cloutier Theresa K, Gokarn Yatin, Zhang Jifeng, Schwenger Walter, Chari Ravi, Calero-Rubio Cesar, Trout Bernhardt L

2021-Jan-15

intermolecular interactions, machine learning, molecular modeling, therapeutic antibodies, viscosity