Investigating Monoclonal Antibody Aggregation Using a Combination of H/DX‐MS and Other Biophysical Measurements. Issue 12 (17th October 2013)

• Record Type: Journal Article
• Authors: Iacob, Roxana E.; Bou‐Assaf, George M.; Makowski, Lee; Engen, John R.; Berkowitz, Steven A.; Houde, Damian
• Is Part Of: Journal of pharmaceutical sciences. Volume 102:Issue 12(2013:Dec.)
• Page Start: 4315
• Page End: 4329
• Publication Date: 2013-10-17
• Subjects: Pharmacy -- Periodicals; 615.1
• DOI: 10.1002/jps.23754
• Languages: English
• ISSNs: 0022-3549

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>To determine how structural changes in antibodies are connected with aggregation, the structural areas of an antibody prone to and/or impacted by aggregation must be identified. In this work, the higher‐order structure and biophysical properties of two different monoclonal antibody (mAb) monomers were compared with their simplest aggregated form, that is, dimers that naturally occurred during normal production and storage conditions. A combination of hydrogen/deuterium exchange mass spectrometry and other biophysical measurements was used to make the comparison. The results show that the dimerization process for one of the mAb monomers (mAb1) displayed no differences in its deuterium uptake between monomer and dimer forms. However, the other mAb monomer (mAb2) showed subtle changes in hydrogen/deuterium exchange as compared with its dimer form. In this case, differences observed were located in specific functional regions of the C_H2 domain and the hinge region between C_H1 and C_H2 domains. The importance and the implications of these changes on the antibody structure and mechanism of aggregation are discussed. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:4315–4329, 2013</p> </abstract>