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Studies from N.J. Boylan and Co-Researchers Yield New Data on Antibodies (Conjugation site heterogeneity causes variable electrostatic properties in...

July 29, 2014



Studies from N.J. Boylan and Co-Researchers Yield New Data on Antibodies (Conjugation site heterogeneity causes variable electrostatic properties in Fc conjugates)

By a News Reporter-Staff News Editor at Life Science Weekly -- Investigators discuss new findings in Immunology. According to news reporting originating in Watertown, Massachusetts, by NewsRx journalists, research stated, "Immunoconjugates, including antibody-drug conjugates and Fc-conjugates, represent a rapidly growing class of therapeutics undergoing clinical development. Despite their growing popularity, the high intrinsic heterogeneity of immunoconjugates often complicates the development process and limits their widespread application."

The news reporters obtained a quote from the research, "In particular, immunoconjugate charge variants exhibit markedly different colloidal stabilities, solubilities, pharmacokinetics, and tissue distributions. Charge variants arise spontaneously due to degradation and, depending on the type of drug, linker, and conjugation site, through drug conjugation. Electrostatic changes in naked antibodies often result in poor performance characteristics, and therefore, charge alterations due to degradation are critical to control. Charge properties are expected to be equally important to producing well-behaved ADCs. Charge-based methods of analysis, such as isoelectric focusing and ion exchange chromatography, are capable of probing the underlying complexities within immunoconjugate drug products. Despite the utility of these methods, there are only a few published reports of charge-based assays applied to immunoconjugates. In the present study, we sought to identify the effects of chemical conjugation on the electrostatic properties of Fc-conjugates. In order to minimize the effects of post-translational modifications (e.g., deamidation), a single Fc charge variant was isolated prior to conjugation of a fluorescent probe, Alexa Fluor 350, to the side chains of lysine residues."

According to the news reporters, the research concluded: "The resulting Fc-conjugates were assessed by a variety of analytical techniques, including isoelectric focusing and ion exchange chromatography, to determine their charge properties."

For more information on this research see: Conjugation site heterogeneity causes variable electrostatic properties in Fc conjugates. Bioconjugate Chemistry, 2013;24(6):1008-16. (American Chemical Society - www.acs.org; Bioconjugate Chemistry - www.pubs.acs.org/journal/bcches)

Our news correspondents report that additional information may be obtained by contacting N.J. Boylan, Wolfe Laboratories, Inc, 134 Coolidge Avenue, Watertown, Massachusetts 02472, United States. Additional authors for this research include W. Zhou, R.J. Proos, T.J. Tolbert, J.L. Wolfe and J.S Laurence (see also Immunology).

Keywords for this news article include: Watertown, Massachusetts, United States, North and Central America, Antibodies, Blood Proteins, Emerging Technologies, Immunoconjugates, Immunology, Immunoproteins, Nanotechnology, Serum Globulins.

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


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Source: Life Science Weekly


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