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<TITLE>Re: [RASMB] non-ideality in velocity [was: interference optics]</TITLE>
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Hi Allen<BR>
<BR>
Good point, especially with regard to antibodies.<BR>
<BR>
However, I fear that the wide world of bio/pharma has yet to come to terms with the need for both reversible and irreversible aggregation to be characterised as universal practice.<BR>
<BR>
Regards<BR>
<BR>
Arthur<BR>
<BR>
<BR>
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Arthur J Rowe<BR>
Professor of Biomolecular Technology<BR>
NCMH Business Centre<BR>
University of Nottingham<BR>
School of Biosciences<BR>
Sutton Bonington<BR>
Leicestershire LE12 5RD UK<BR>
<BR>
Tel: +44 (0)115 951 6156<BR>
+44 (0)116 271 4502<BR>
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email: arthur.rowe@nottingham.ac.uk<BR>
Web: www.nottingham.ac.uk/ncmh/business<BR>
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<TT>Hello Borries -<BR>
<BR>
At 11:21 AM 4/8/2008, you wrote:<BR>
<BR>
>So my question is: Why are drug companies interested in the reversible<BR>
>kind, or is there another reason to measure at high concentration?<BR>
<BR>
1. Reversible self-association causes large increases in viscosity <BR>
(see recent work of Steve Shire and coworkers), which in turn causes <BR>
problems in administration of concentrated immunoglobulin via <BR>
injection through narrow bore needles. Different monoclonal <BR>
antibodies have significantly different tendencies to reversibly <BR>
self-associate at high concentration. Thus screening of candidate <BR>
engineered antibodies for tendency to reversibly self-associate at <BR>
high concentration is an essential part of the drug development process.<BR>
<BR>
2. Directly following administration there exists a bolus of locally <BR>
highly concentrated antibody at the site of administration which <BR>
requires time to dissipate. Reversibly formed aggregates therefore <BR>
exist with a significant lifetime. The physiological effects of such <BR>
aggregates are unknown, but it is possible that some oligomeric <BR>
species may be mistakenly identified as foreign proteins and <BR>
therefore break immune tolerance.<BR>
<BR>
For both of these reasons the FDA wants pharmaceutical companies to <BR>
characterize formulations of monoclonal antibodies with respect to <BR>
both reversible and irreversible self-association. The former <BR>
requires measurement at high concentration.<BR>
<BR>
Allen <BR>
<BR>
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