Observation of Small Cluster Formation in Concentrated Monoclonal Antibody Solutions and Its Implications to Solution Viscosity. Yearley, E. J., Godfrin, P. D., Perevozchikova, T., Zhang, H., Falus, P., Porcar, L., Nagao, M., Curtis, J. E., Gawande, P., Taing, R., Zarraga, I. E., Wagner, N. J., & Liu, Y. Biophysical Journal, 106(8):1763–1770, April, 2014. Place: Cambridge Publisher: Cell Press WOS:000334567300027doi abstract bibtex Monoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is hypothesized that some concentrated mAb solutions exhibit formation of a solution phase consisting of reversibly self-associated aggregates (or reversible clusters), which is speculated to be responsible for their distinct solution properties. Here, we report direct observation of reversible clusters in concentrated solutions of mAbs using neutron spin echo. Specifically, a stable nnAb solution is studied across a transition from dispersed monomers in dilute solution to clustered states at more concentrated conditions, where clusters of a preferred size are observed. Once mAb clusters have formed, their size, in contrast to that observed in typical globular protein solutions, is observed to remain nearly constant over a wide range of concentrations. Our results not only conclusively establish a clear relationship between the undesirable high viscosity of some mAb solutions and the formation of reversible clusters with extended open structures, but also directly observe self-assembled mAb protein clusters of preferred small finite size similar to that in micelle formation that dominate the properties of concentrated mAb solutions.
@article{yearley_observation_2014,
title = {Observation of {Small} {Cluster} {Formation} in {Concentrated} {Monoclonal} {Antibody} {Solutions} and {Its} {Implications} to {Solution} {Viscosity}},
volume = {106},
issn = {0006-3495},
doi = {10.1016/j.bpj.2014.02.036},
abstract = {Monoclonal antibodies (mAbs) are a major class of biopharmaceuticals. It is hypothesized that some concentrated mAb solutions exhibit formation of a solution phase consisting of reversibly self-associated aggregates (or reversible clusters), which is speculated to be responsible for their distinct solution properties. Here, we report direct observation of reversible clusters in concentrated solutions of mAbs using neutron spin echo. Specifically, a stable nnAb solution is studied across a transition from dispersed monomers in dilute solution to clustered states at more concentrated conditions, where clusters of a preferred size are observed. Once mAb clusters have formed, their size, in contrast to that observed in typical globular protein solutions, is observed to remain nearly constant over a wide range of concentrations. Our results not only conclusively establish a clear relationship between the undesirable high viscosity of some mAb solutions and the formation of reversible clusters with extended open structures, but also directly observe self-assembled mAb protein clusters of preferred small finite size similar to that in micelle formation that dominate the properties of concentrated mAb solutions.},
language = {English},
number = {8},
journal = {Biophysical Journal},
author = {Yearley, Eric J. and Godfrin, Paul D. and Perevozchikova, Tatiana and Zhang, Hailiang and Falus, Peter and Porcar, Lionel and Nagao, Michihiro and Curtis, Joseph E. and Gawande, Pradad and Taing, Rosalynn and Zarraga, Isidro E. and Wagner, Norman J. and Liu, Yun},
month = apr,
year = {2014},
note = {Place: Cambridge
Publisher: Cell Press
WOS:000334567300027},
keywords = {angle neutron-scattering, colloids, competing interactions, dynamics, formulation, phosphoglycerate kinase, protein solutions, self-association, spin-echo spectroscopy, therapeutics},
pages = {1763--1770}
}
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