[RASMB] non-ideality in velocity [was: interference optics]

[Allen Minton]

Hello Borries -

At 11:21 AM 4/8/2008, you wrote:

>So my question is: Why are drug companies interested in the reversible
>kind, or is there another reason to measure at high concentration?

1. Reversible self-association causes large increases in viscosity 
(see recent work of Steve Shire and coworkers), which in turn causes 
problems in administration of concentrated immunoglobulin via 
injection through narrow bore needles.  Different monoclonal 
antibodies have significantly different tendencies to reversibly 
self-associate at high concentration.  Thus screening of candidate 
engineered antibodies for tendency to reversibly self-associate at 
high concentration is an essential part of the drug development process.

2. Directly following administration there exists a bolus of locally 
highly concentrated antibody at the site of administration which 
requires time to dissipate.  Reversibly formed aggregates therefore 
exist with a significant lifetime.  The physiological effects of such 
aggregates are unknown, but it is possible that some oligomeric 
species may be mistakenly identified as foreign proteins and 
therefore break immune tolerance.

For both of these reasons the FDA wants pharmaceutical companies to 
characterize formulations of monoclonal antibodies with respect to 
both reversible and irreversible self-association.   The former 
requires measurement at high concentration.

Allen