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Assessment of Antibody Self-Interaction by Bio-Layer-Interferometry as a Tool for Early Stage Formulation Development

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Abstract

Purpose

To speed up the drug development process in the biopharmaceutical industry, high throughput methods are indispensable for assessing drug candidates and potential lead formulations, in particular during late stages of discovery and early phases of development. This study aimed to establish a bio-layer-interferometry based high throughput assay for assessing formulation dependent mAb self-interaction (SI-BLI) and to compare the results with kD values obtained by dynamic light scattering (DLS).

Methods

Self-interaction of proprietary and commercially available mAbs was analyzed by SI-BLI and dynamic light scattering (DLS).

Results

We found significant correlations of the SI-BLI results and kD-values obtained by DLS for both, different mAbs in one platform formulation and for mAbs formulated in several buffer compositions. In total, we assessed self-interaction propensity of different mAbs in 58 formulations and found significant Pearson correlation (p < 0.05) between kD and results of SI-BLI.

Conclusions

The SI-BLI results correlate with kD and enable fast ranking of both different drug candidates and potential lead formulations. Thus, SI-BLI might decrease the risk to lose potent mAb candidates during transition from discovery to development, and help to accelerate the development of high concentration liquid formulations.

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Abbreviations

AUC:

Analytical ultracentrifugation

BLI:

Bio-layer-interferometry

DLS:

Dynamic light scattering

HCLF:

high (protein) concentration liquid formulation

HDX-MS:

Hydrogen-Deuterium exchange mass spectrometry

mAb:

Monoclonal antibody

PBS:

Phosphate buffered saline

SI-BLI:

Self-interaction assay based on Bio-layer-interferometry

SIC:

Self-interaction chromatography

SLS:

Static Light Scattering

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Acknowledgements

This study was part of the project “Self-Interaction and targeted Engineering of monoclonal antibodies (Self-I-E)”. This project is funded by the Bayerische Forschungsstiftung. The authors would like to thank the whole Protein Sciences & CMC Department of MorphoSys AG for their outstanding support. In addition, the authors would like to thank Dr. Daniel Weinfurtner and Dr. Roy Eylenstein for their support during the initial phase of this project.

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Correspondence to Wolfgang Frieß.

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Domnowski, M., Jaehrling, J. & Frieß, W. Assessment of Antibody Self-Interaction by Bio-Layer-Interferometry as a Tool for Early Stage Formulation Development. Pharm Res 37, 29 (2020). https://doi.org/10.1007/s11095-019-2722-4

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Keywords

  • antibody
  • bio-layer-interferometry
  • diffusion interaction parameter
  • high concentration formulation
  • Self-interaction