Biophysical characterization of binary therapeutic monoclonal antibody mixtures
- Author
- Dennis Krieg, Carolin Berner, Gerhard Winter and Hristo Svilenov (UGent)
- Organization
- Abstract
- Coformulations containing two therapeutic monoclonal antibodies (mAbs) could offer various benefits like enhanced therapeutic efficacy and better patient compliance. However, there are very few published studies on coformulations and binary mixtures of mAbs. It remains unclear to what extent mAbs with different physicochemical properties can be combined in solution without detrimental effects on protein stability. Here, we present a study including six model mAbs of the IgG1 subclass that are commercially available. In silico and biophysical characterization shows that the proteins have different physicochemical properties. Thus, their combinations represent various scenarios for coformulation development. We prepared all possible binary mixtures of the six mAbs and determined several biophysical parameters that are assessed during early-stage protein drug product development. The measured biophysical parameters are indicative of the conformational protein stability (inflection points of the thermal protein unfolding transitions) and the colloidal protein stability (aggregation onset temperatures and interaction parameter kD from dynamic light scattering). Remarkably, all 15 binary mAb mixtures do not exhibit biophysical parameters that indicate inferior conformational or colloidal stability compared to the least stable mAb in the mixture. Our findings suggest that the coformulation of some therapeutic monoclonal antibodies of the IgG1 subclass could be possible in a straightforward way as severe detrimental effects on the stability of these proteins in binary mixtures were not observed.
- Keywords
- Drug Discovery, Pharmaceutical Science, Molecular Medicine, monoclonal antibodies, antibody mixtures, coformulation, stability, biophysical properties, VISCOSITY BEHAVIOR, CHARGE VARIANTS, LIQUID-LIQUID, PROTEIN, COAGGREGATION, PREDICTION, STABILITY, SEQUENCE, GOVERN, TOOL
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8741216
- MLA
- Krieg, Dennis, et al. “Biophysical Characterization of Binary Therapeutic Monoclonal Antibody Mixtures.” MOLECULAR PHARMACEUTICS, vol. 17, no. 8, 2020, pp. 2971–86, doi:10.1021/acs.molpharmaceut.0c00370.
- APA
- Krieg, D., Berner, C., Winter, G., & Svilenov, H. (2020). Biophysical characterization of binary therapeutic monoclonal antibody mixtures. MOLECULAR PHARMACEUTICS, 17(8), 2971–2986. https://doi.org/10.1021/acs.molpharmaceut.0c00370
- Chicago author-date
- Krieg, Dennis, Carolin Berner, Gerhard Winter, and Hristo Svilenov. 2020. “Biophysical Characterization of Binary Therapeutic Monoclonal Antibody Mixtures.” MOLECULAR PHARMACEUTICS 17 (8): 2971–86. https://doi.org/10.1021/acs.molpharmaceut.0c00370.
- Chicago author-date (all authors)
- Krieg, Dennis, Carolin Berner, Gerhard Winter, and Hristo Svilenov. 2020. “Biophysical Characterization of Binary Therapeutic Monoclonal Antibody Mixtures.” MOLECULAR PHARMACEUTICS 17 (8): 2971–2986. doi:10.1021/acs.molpharmaceut.0c00370.
- Vancouver
- 1.Krieg D, Berner C, Winter G, Svilenov H. Biophysical characterization of binary therapeutic monoclonal antibody mixtures. MOLECULAR PHARMACEUTICS. 2020;17(8):2971–86.
- IEEE
- [1]D. Krieg, C. Berner, G. Winter, and H. Svilenov, “Biophysical characterization of binary therapeutic monoclonal antibody mixtures,” MOLECULAR PHARMACEUTICS, vol. 17, no. 8, pp. 2971–2986, 2020.
@article{8741216,
abstract = {{Coformulations containing two therapeutic monoclonal antibodies (mAbs) could offer various benefits like enhanced therapeutic efficacy and better patient compliance. However, there are very few published studies on coformulations and binary mixtures of mAbs. It remains unclear to what extent mAbs with different physicochemical properties can be combined in solution without detrimental effects on protein stability. Here, we present a study including six model mAbs of the IgG1 subclass that are commercially available. In silico and biophysical characterization shows that the proteins have different physicochemical properties. Thus, their combinations represent various scenarios for coformulation development. We prepared all possible binary mixtures of the six mAbs and determined several biophysical parameters that are assessed during early-stage protein drug product development. The measured biophysical parameters are indicative of the conformational protein stability (inflection points of the thermal protein unfolding transitions) and the colloidal protein stability (aggregation onset temperatures and interaction parameter kD from dynamic light scattering). Remarkably, all 15 binary mAb mixtures do not exhibit biophysical parameters that indicate inferior conformational or colloidal stability compared to the least stable mAb in the mixture. Our findings suggest that the coformulation of some therapeutic monoclonal antibodies of the IgG1 subclass could be possible in a straightforward way as severe detrimental effects on the stability of these proteins in binary mixtures were not observed.}},
author = {{Krieg, Dennis and Berner, Carolin and Winter, Gerhard and Svilenov, Hristo}},
issn = {{1543-8384}},
journal = {{MOLECULAR PHARMACEUTICS}},
keywords = {{Drug Discovery,Pharmaceutical Science,Molecular Medicine,monoclonal antibodies,antibody mixtures,coformulation,stability,biophysical properties,VISCOSITY BEHAVIOR,CHARGE VARIANTS,LIQUID-LIQUID,PROTEIN,COAGGREGATION,PREDICTION,STABILITY,SEQUENCE,GOVERN,TOOL}},
language = {{eng}},
number = {{8}},
pages = {{2971--2986}},
title = {{Biophysical characterization of binary therapeutic monoclonal antibody mixtures}},
url = {{http://doi.org/10.1021/acs.molpharmaceut.0c00370}},
volume = {{17}},
year = {{2020}},
}
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