期刊
JOURNAL OF PHARMACEUTICAL SCIENCES
卷 103, 期 11, 页码 3356-3363出版社
WILEY
DOI: 10.1002/jps.24130
关键词
high throughput technologies; biophysical methods; solubility; protein aggregation; protein formulation; physical stability; viscosity; IgG; V-H; V-L; Fab; CDR; complementarity-determining region
资金
- NSF (CBET) [0954450, 1159943]
- NIH [R01GM104130]
- MedImmune
- Eli Lilly
- Bristol-Myers Squibb
- Janssen Biotech
- Merck
- Genentech
- Amgen
- Pfizer
- Adimab
- Abbott
- Bayer
- Roche
- DuPont
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [0954450] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys
- Directorate For Engineering [1159943] Funding Source: National Science Foundation
A limitation of using mAbs as therapeutic molecules is their propensity to associate with themselves and/or with other molecules via nonaffinity (colloidal) interactions. This can lead to a variety of problems ranging from low solubility and high viscosity to off-target binding and fast antibody clearance. Measuring such colloidal interactions is challenging given that they are weak and potentially involve diverse target molecules. Nevertheless, assessing these weak interactionsespecially during early antibody discovery and lead candidate optimizationis critical to preventing problems that can arise later in the development process. Here we review advances in developing and implementing sensitive methods for measuring antibody colloidal interactions as well as using these measurements for guiding antibody selection and engineering. These systematic efforts to minimize nonaffinity interactions are expected to yield more effective and stable mAbs for diverse therapeutic applications. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:3356-3363, 2014
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