Zhang, H;
Dalby, PA;
(2020)
Stability enhancement in a mAb and Fab coformulation.
Scientific Reports
, 10
, Article 21129. 10.1038/s41598-020-77989-w.
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Abstract
Multiple therapeutic proteins can be combined into a single dose for synergistic targeting to multiple sites of action. Such proteins would be mixed in dose-specific ratios to provide the correct potency for each component, and yet the formulations must also preserve their activity and keep degradation to a minimum. Mixing different therapeutic proteins could adversely affect their stability, and reduce the shelf life of each individual component, making the control of such products very challenging. In this study, a therapeutic monoclonal antibody and a related Fab fragment, were combined to investigate the impact of coformulation on their degradation kinetics. Under mildly destabilizing conditions, these proteins were found to protect each other from degradation. The protective effect appeared to originate from the interaction of Fab and IgG1 in small soluble oligomers, or through the rapid coalescence of pre-existing monomeric IgG1 nuclei into a dead-end aggregate, rather than through macromolecular crowding or diffusion-limitations.
| Type: | Article |
|---|---|
| Title: | Stability enhancement in a mAb and Fab coformulation |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-020-77989-w |
| Publisher version: | https://doi.org/10.1038/s41598-020-77989-w |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Biochemistry, Biological techniques, Biotechnology |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10116874 |
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