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Application of Affinity-Capture Self-Interaction Nanoparticle Spectroscopy in Predicting Protein Stability, Especially for Co-Formulated Antibodies

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Abstract

Purpose

From traditional monoclonal antibodies to more and more complex mAb-based formulations, biopharmaceutical faces one challenge after another. To avoid these issues, identification of therapeutic proteins in the initial discovery process that has high stability and low self-interaction would simplify the development of safe and effective antibody therapeutics.

Method

Affinity-capture self-interaction nanoparticle spectroscopy (AC-SINS) is a new prediction method capable of identifying mAbs with different self-association propensity. In this study, 10 formulated monoclonal antibody (mAb) therapeutics include different mAb isotypes and co-formulated antibodies were measured by AC-SINS and some biophysical methods to predict protein stability. The prediction results of all 10 mAbs were compared to their stability data (Δ%monomer and Δ%HMWs) at accelerated (25°C and 40°C) and long-term storage conditions (4°C) as measured by size exclusion chromatography.

Result

AC-SINS method has a good predictive correlation with each mAbs and co-formulated antibodies. There were no physicochemical, intermolecular, or biological interactions that occurred between the two components of co-formulated antibodies which confirmed by Analytical ultracentrifugation (AUC).

Conclusion

Here we discuss the correlation between each method and protein stability, and also use AC-SINS assay to predict the stability of co-formulated antibodies for the first time. This may be an effective way to predict the stability of these complex mAb-based formulations such as co-formulated mAbs.

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Abbreviations

AC-SINS :

Affinity-capture self-interaction nanoparticle spectroscopy

AUC :

Analytical ultracentrifugation

mAb :

Monoclonal antibody

PPI :

Protein-protein interaction

SEC :

Size-exclusion chromatography

SE :

Sedimentation equilibrium experiment

SV :

Sedimentation velocity experiment

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Acknowledgments

This research was funded by Shanghai Hengrui Pharmaceutical Co., Ltd. The authors declare no conflicts of interest

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Authors and Affiliations

  1. School of Pharmacy, China Pharmaceutical University, Nanjing, 211198, China

    Meng Zhou & Piaoyang Sun

  2. Shanghai Hengrui Pharmaceutical Co., Ltd., Shanghai, 200245, China

    Zhen Yan, Hao Li, Xun Liu & Piaoyang Sun

Authors
  1. Meng Zhou
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  2. Zhen Yan
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  3. Hao Li
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  4. Xun Liu
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Correspondence to Xun Liu or Piaoyang Sun.

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Zhou, M., Yan, Z., Li, H. et al. Application of Affinity-Capture Self-Interaction Nanoparticle Spectroscopy in Predicting Protein Stability, Especially for Co-Formulated Antibodies. Pharm Res 38, 721–732 (2021). https://doi.org/10.1007/s11095-021-03026-8

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  • DOI: https://doi.org/10.1007/s11095-021-03026-8

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