Comparison of Huggins Coefficients and Osmotic Second Virial Coefficients of Buffered Solutions of Monoclonal Antibodies
Abstract
:1. Introduction
Brief Overview of the Complexities of Protein–Protein Interactions and Protein Association
2. Materials and Methods
2.1. Size Exclusion Chromatography (SEC)
2.2. Capillary Iso-Electric Focusing (cIEF)
2.3. Viscometry
2.4. Osmotic Second Virial Coefficient Determination
2.5. Hydrated Protein Molecular Volume: Atomistic Monte Carlo Computer Simulations
3. Results
3.1. Biophysical Characterization
Size Exclusion Chromatography (SEC)
3.2. Antibody Solution Viscosity and Its Reduction
4. Discussion
Comparison of Antibody Solution Measurements with Flexible Polymer and Sticky Sphere Kh Models
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Antibody | PDB ID | Molar Mass (kDa) | Protein Iso-Electric Point Main Peak/Range | Buffer Composition | Net Ionic Strength (mM) |
---|---|---|---|---|---|
mAb-1 | 4LST | 148 | 9.06; 8.78–9.25 | 25 mM Na citrate, 50 mM NaCl,150 mM arginine HCl, pH 5.8 | 278.8 * |
mAb-2 | 5FYJ | 151 | 9.30; 9.14–9.59 | 50 mM histidine HCl, 50 mM NaCl, 5 % (w/v) sucrose, 2.5% (w/v) sorbitol, pH 6.8 | 56.9 |
mAb-3 | 5TE4 | 158 | 9.13; 8.99–9.47 | 10 mM Na citrate, 50 mM NaCl 150 mM arginine HCl, 0.002% (w/v) polysorbate 80, pH 6.5 | 246.3 |
mAb-3 (pH Variation) | 5TE4 | 158 | - | 20 mM histidine acetate, 50 mM NaCl 4.2 ≤ pH ≤ 6.2 | 70 † |
System | % Monomer | % Fragment | % Aggregate |
---|---|---|---|
mAb-1 formulation | 99.0 | 0.0 | 1.0 |
mAb-2 formulation | 98.0 | 0.0 | 2.0 |
mAb-3 formulation | 99.0 | 0.0 | 1.0 |
mAb-3 pH 4.2 | 98.8 | 0.4 | 0.8 |
mAb-3 pH 4.5 | 98.6 | 0.3 | 1.1 |
mAb-3 pH 4.9 | 97.8 | 0.2 | 2.0 |
mAb-3 pH 5.4 | 97.8 | 0.0 | 2.2 |
mAb-3 pH 5.9 | 97.1 | 0.0 | 2.9 |
mAb-3 pH 6.2 | 95.8 | 0.0 | 4.2 |
Antibody in Buffered Formulation | Huggins Coefficient, kH 2,3,4 | Intrinsic Viscosity [η], mL/g 1,2,4 | [η] Volume Fraction Units | Ψ ≡ B22/B22,ST 1,5 |
---|---|---|---|---|
mAb-1 | 3.3 ± 1.6 | 6.8 ± 1.0 | 6.0 ± 0.9 | 0.47 ± 0.14 |
mAb-2 | 0.9 ± 0.2 | 12.4 ± 0.7 | 10.9 ± 0.6 | 0.50 ± 0.13 |
mAb-3 (at fixed pH 6.5) | 3.6 ± 0.8 | 6.8 ± 0.5 | 6.0 ± 0.4 | 0.68 ± 0.15 |
mAb-3 Solution pH | Huggins Coefficient, kH 1–3 | Intrinsic Viscosity [η] (mL/g) 1,3 | [η] Volume Fraction Units | Ψ = B22/B22,ST |
---|---|---|---|---|
4.2 | 2.1 ± 0.3 | 7.7 ± 0.3 | 6.8 ± 0.3 | 1.25 ± 0.26 |
4.5 | 7.6 ± 3.1 | 5.4 ± 0.8 | 4.7 ± 0.7 | 1.15 ± 0.31 |
4.9 | 5.6 ± 2.7 | 7.1 ± 1.3 | 6.2 ± 1.1 | 0.68 ± 0.18 |
5.4 | 5.2 ± 2.7 | 6.7 ± 1.2 | 5.9 ± 1.0 | 0.57 ± 0.14 |
5.9 | 2.4 ± 1.7 | 9.0 ± 1.9 | 7.9 ± 1.7 | 0.48 ± 0.11 |
6.2 | 3.8 ± 1.9 | 7.2 ± 1.2 | 6.3 ± 1.1 | 0.53 ± 0.50 |
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Pathak, J.A.; Nugent, S.; Bender, M.F.; Roberts, C.J.; Curtis, R.J.; Douglas, J.F. Comparison of Huggins Coefficients and Osmotic Second Virial Coefficients of Buffered Solutions of Monoclonal Antibodies. Polymers 2021, 13, 601. https://doi.org/10.3390/polym13040601
Pathak JA, Nugent S, Bender MF, Roberts CJ, Curtis RJ, Douglas JF. Comparison of Huggins Coefficients and Osmotic Second Virial Coefficients of Buffered Solutions of Monoclonal Antibodies. Polymers. 2021; 13(4):601. https://doi.org/10.3390/polym13040601
Chicago/Turabian StylePathak, Jai A., Sean Nugent, Michael F. Bender, Christopher J. Roberts, Robin J. Curtis, and Jack F. Douglas. 2021. "Comparison of Huggins Coefficients and Osmotic Second Virial Coefficients of Buffered Solutions of Monoclonal Antibodies" Polymers 13, no. 4: 601. https://doi.org/10.3390/polym13040601
APA StylePathak, J. A., Nugent, S., Bender, M. F., Roberts, C. J., Curtis, R. J., & Douglas, J. F. (2021). Comparison of Huggins Coefficients and Osmotic Second Virial Coefficients of Buffered Solutions of Monoclonal Antibodies. Polymers, 13(4), 601. https://doi.org/10.3390/polym13040601