Leveraging multi-modal feature learning for predictions of antibody viscosity.

Journal: mAbs
PMID:

Abstract

The shift toward subcutaneous administration for biologic therapeutics has gained momentum due to its patient-friendly nature, convenience, reduced healthcare burden, and improved compliance compared to traditional intravenous infusions. However, a significant challenge associated with this transition is managing the viscosity of the administered solutions. High viscosity poses substantial development and manufacturability challenges, directly affecting patients by increasing injection time and causing pain at the injection site. Furthermore, high viscosity formulations can prolong residence time at the injection site, affecting absorption kinetics and potentially altering the intended pharmacological profile and therapeutic efficacy of the biologic candidate. Here, we report the application of a multimodal feature learning workflow for predicting the viscosity of antibodies in therapeutics discovery. It integrates multiple data sources including sequence, structural, physicochemical properties, as well as embeddings from a language model. This approach enables the model to learn from various underlying rules, such as physicochemical rules from molecular simulations and protein evolutionary patterns captured by large, pre-trained deep learning models. By comparing the effectiveness of this approach to other selected published viscosity prediction methods, this study provides insights into their intrinsic viscosity predictive potential and usability in early-stage therapeutics antibody development pipelines.

Authors

  • Krishna D B Anapindi
    Protein Therapeutics, Gilead Sciences, Foster City, CA, USA.
  • Kai Liu
    College of Marine Sciences, Shanghai Ocean University, Shanghai 201306, China.
  • Willie Wang
    Protein Therapeutics, Gilead Sciences, Foster City, CA, USA.
  • Yao Yu
    AbbVie Inc, North Chicago, IL, USA.
  • Yan He
    School of Biology & Engineering, Guizhou Medical University, Guiyang, Guizhou Province, China.
  • Edward J Hsieh
    Protein Therapeutics, Gilead Sciences, Foster City, CA, USA.
  • Ying Huang
    Department of Otolaryngology, Head and Neck Surgery, Affiliated Hospital of Southwest Medical University Luzhou, Sichuan, China.
  • Daniela Tomazela
    Protein Therapeutics, Gilead Sciences, Foster City, CA, USA.