Linked Life Data

16315222

Source:http://linkedlifedata.com/resource/pubmed/id/16315222

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-12-5
pubmed:abstractText
Understanding the intermolecular products of antibodies as a consequence of host-cell expression, aging, and heat-stress can be insightful especially when it involves the development of a stable biopharmaceutical product. The dimerized form of Epratuzumab (an IgG(1) antibody) with a molecular mass of approximately 300 kDa (twice the monomer antibody molecular weight of approximately 150 kDa) was examined to gain a better perspective of its properties pertaining to structure and activity. The nascent dimer was shown to partially dissociate upon incubation at 30 degrees C and 37 degrees C, exhibit no discernable alteration of structure (i.e., secondary or tertiary structure based on CD and 2nd derivative UV spectroscopy), have approximately 70% covalent forms (based upon CE-SDS results) and manifest twofold higher activity relative to the active monomer form (on a weight basis the dimer and monomer have equal activity). Interestingly, these properties were not attributed to a single dimer species, but rather to a more complex dimer assembly. The Epratuzumab dimer was digested with papain to reveal three uniquely dimerized aggregates. The relative molar distribution of Fab:Fab, Fc:Fc, and Fab:Fc was found to be 4:3:8, respectively. The data suggest that all three predominantly covalent dimer adducts are capable of full activity, shedding light on their complex nature and showing that their target specificity was unaltered. ESI-MS data indicated the presence of remnant levels of noncovalent dimers for all three dimerized forms. Material aged at 37 degrees C exhibited a similar papain digest molar distribution of the three dimerized forms, except with enhanced chemical heterogeneity and an increase in covalent forms to approximately 84%.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-3549
pubmed:author
pubmed:issnType
Print
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
126-45
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Active dimer of Epratuzumab provides insight into the complex nature of an antibody aggregate.
pubmed:affiliation
Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA. remmeler@amgen.com
pubmed:publicationType
Journal Article