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Human antibody Fc deamidation in vivo.

Y Diana YD Liu, Jian Zhang JZ van Enk, and Gregory C GC Flynn

Biologicals 37(5):313-22 (2009) PMID 19608432

Protein and peptide deamidation occurs spontaneously in vitro under relatively mild conditions. For antibodies and other therapeutic proteins, great effort is placed in manufacturing and storage to minimize this form of degradation. Concern has been especially great in cases where deamidation has been shown to impact protein activity. Here we monitored asparagine deamidation from a recombinant human antibody in humans and found that among the conserved sites, only Asn 384 deamidated at an appreciable rate. Under physiological temperature and pH conditions, in vitro antibody deamidation followed similar kinetics, indicating that simple incubation reactions may be used to model in vivo behavior. Endogenous IgG isolated from human serum possessed 23% deamidation at this site, further demonstrating that this modification is naturally occurring. Thus, deamidation generated in manufacturing and storage does not fully determine the patient exposure to the attribute. Instead, pharmacokinetic data along with the deamidation kinetics are combined to predict patient exposure. The deamidation rate can also be used to estimate the serum lifetime of antibodies. This approach could potentially be used to estimate turnover for other cellular or extracellular proteins.

Copyright © 2009 Elsevier Ltd. All rights reserved.

DOI: 10.1016/j.biologicals.2009.06.001
Version: za2963e q8zaf q8zba q8zcc q8zda q8ze7 q8zfc q8zg9

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