Accelerating high-concentration monoclonal antibody development with large-scale viscosity data and ensemble deep learning

MAbs. 2025 Dec;17(1):2483944. doi: 10.1080/19420862.2025.2483944. Epub 2025 Apr 1.

Abstract

Highly concentrated antibody solutions are necessary for developing subcutaneous injections but often exhibit high viscosities, posing challenges in antibody-drug development, manufacturing, and administration. Previous computational models were only limited to a few dozen data points for training, a bottleneck for generalizability. In this study, we measured the viscosity of a panel of 229 monoclonal antibodies (mAbs) to develop predictive models for high concentration mAb screening. We developed DeepViscosity, consisting of 102 ensemble artificial neural network models to classify low-viscosity (≤20 cP) and high-viscosity (>20 cP) mAbs at 150 mg/mL, using 30 features from a sequence-based DeepSP model. Two independent test sets, comprising 16 and 38 mAbs with known experimental viscosity, were used to assess DeepViscosity's generalizability. The model exhibited an accuracy of 87.5% and 89.5% on both test sets, respectively, surpassing other predictive methods. DeepViscosity will facilitate early-stage antibody development to select low-viscosity antibodies for improved manufacturability and formulation properties, critical for subcutaneous drug delivery. The webserver-based application can be freely accessed via https://devpred.onrender.com/DeepViscosity.

Keywords: Antibody viscosity; ensemble deep learning; high-concentration formulations; monoclonal antibodies.

MeSH terms

  • Antibodies, Monoclonal* / chemistry
  • Deep Learning*
  • Drug Development* / methods
  • Humans
  • Neural Networks, Computer
  • Viscosity

Substances

  • Antibodies, Monoclonal