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Understanding Therapeutic Monoclonal Antibody Aggregation Mechanisms through Biophysical, Biochemical and Biological Characterization of Two Types of Immunoglobulin G Dimers
dc.contributor.advisor | Volkin, David | |
dc.contributor.author | Woods, Christopher E. | |
dc.date.accessioned | 2016-10-11T19:10:54Z | |
dc.date.available | 2016-10-11T19:10:54Z | |
dc.date.issued | 2015-12-31 | |
dc.date.submitted | 2015 | |
dc.identifier.other | http://dissertations.umi.com/ku:14272 | |
dc.identifier.uri | http://hdl.handle.net/1808/21660 | |
dc.description.abstract | Aggregation has been identified as one of the major degradation pathways that affect the quality and efficacy of protein therapeutics. Dimers are one of the predominant oligomeric species found in monoclonal antibody (mAb) based products, whose formation can occur both during processing and long-term storage, and following exposure to certain accelerated stress conditions. It has been hypothesized that these dimeric species could be the initial step on the mAb protein aggregation pathway, but this has been difficult to establish since mAb dimers can be a heterogeneous population of molecules. In this study, two mAb dimer species were generated and isolated from IgG2 monoclonal antibody samples, one upon long-term storage and the other from elevated stress conditions. The dimer-enriched fractions were characterized for protein conformation, morphology, structural integrity and bioactivity. The results revealed both common properties and unique differences between the two types of mAb dimers generated under these two different conditions. The findings of this study provide insights towards greater understanding of the possible causes of dimer formation under native storage and thermal stress conditions for this IgG2 mAb, and two possible mechanisms of dimer formation are proposed. | |
dc.format.extent | 70 pages | |
dc.language.iso | en | |
dc.publisher | University of Kansas | |
dc.rights | Copyright held by the author. | |
dc.subject | Pharmaceutical sciences | |
dc.subject | Pharmacology | |
dc.subject | Biochemistry | |
dc.subject | Biophysical Analysis | |
dc.subject | Hydrogen-Deuterium Exchange | |
dc.subject | Immunoglobulin G | |
dc.subject | Monoclonal Antibody | |
dc.subject | Protein Aggregation | |
dc.title | Understanding Therapeutic Monoclonal Antibody Aggregation Mechanisms through Biophysical, Biochemical and Biological Characterization of Two Types of Immunoglobulin G Dimers | |
dc.type | Thesis | |
dc.contributor.cmtemember | He, Feng | |
dc.contributor.cmtemember | Tolbert, Thomas | |
dc.thesis.degreeDiscipline | Pharmaceutical Chemistry | |
dc.thesis.degreeLevel | M.S. | |
dc.provenance | 04/05/2017: The ETD release form is attached to this record as a license file. | |
dc.rights.accessrights | openAccess |
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Pharmaceutical Chemistry Dissertations and Theses [141]
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Theses [4088]