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<DIV dir=ltr align=left><SPAN class=921325815-10042008><FONT face=Arial
color=#0000ff size=2>There is an important distinction between the sort of
thermodynamic characterization of drugs like Jack Correia's work on drug
binding to tubulin, which is highly relevant to the actual mechanism of
action of that drug, versus characterizing rapidly-reversible self-association
of protein therapeutics. Even the regulatory agencies agree that such
rapidly-reversible associations may have little or no relevance to safety
to efficacy, and they have nothing to do with the drug's mechanism of
action, so the reasons and motivations to understand the thermodynamic
details are quite different. </FONT></SPAN></DIV>
<DIV dir=ltr align=left><SPAN class=921325815-10042008><FONT face=Arial
color=#0000ff size=2></FONT></SPAN> </DIV>
<DIV dir=ltr align=left><SPAN class=921325815-10042008><FONT face=Arial
color=#0000ff size=2>With respect to mechanisms of action there has been
considerable work on thermodynamics of protein-protein interactions by the
biotech industry, and a fair amount of that has even been published, such
as the receptor-hormone studies by our former group at Amgen and
several other groups. For many monoclonal antibodies even the kinetics
of the association-dissociation reactions with their target antigens have
been thoroughly explored (often via BIAcore) because those rates are thought to
be relevant to efficacy.</FONT></SPAN></DIV>
<DIV dir=ltr align=left><SPAN class=921325815-10042008><FONT face=Arial
color=#0000ff size=2></FONT></SPAN> </DIV>
<DIV dir=ltr align=left><SPAN class=921325815-10042008><FONT face=Arial
color=#0000ff size=2>So the bottom line is that my comments, and I think
Arthur's too, were not intended to imply that the biotech industry has
little interest in thermodynamics per se, but were more specific to the
reversible aggregation topic.</FONT></SPAN></DIV>
<DIV><SPAN class=921325815-10042008><FONT face=Arial color=#0000ff
size=2></FONT></SPAN> </DIV>
<DIV><SPAN class=921325815-10042008><FONT face=Arial color=#0000ff
size=2>John</FONT></SPAN></DIV>
<DIV dir=ltr align=left><BR></DIV>
<DIV class=OutlookMessageHeader lang=en-us dir=ltr align=left>
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<FONT face=Tahoma size=2><B>From:</B> rasmb-bounces@rasmb.bbri.org
[mailto:rasmb-bounces@rasmb.bbri.org] <B>On Behalf Of </B>Arthur
Rowe<BR><B>Sent:</B> Thursday, April 10, 2008 3:26 AM<BR><B>To:</B> John
Correia<BR><B>Cc:</B> rasmb@server1.bbri.org<BR><B>Subject:</B> Re: [RASMB]
analysis of biotech samples [was: non-ideality in SV]<BR></FONT><BR></DIV>
<DIV></DIV>
<BLOCKQUOTE><FONT color=#800000>And just a very little response, Jack! We do
get some extremely interesting samples to work on in the NCMH Business Centre,
and obviously where appropriate we can, for our own satisfaction and benefit*,
pursue analysis with all the rigour we can summon up, whether the ultimate
client actually wants it doing or not.<BR><BR>But the image of our sitting
down for a cosy chat and earnest scientific discussion with the said client's
research director is not always quite where it is at. More often we are
recruited by an agency, whose expertise is in finding analytical services
which meet a client company's needs. And beyond that, the agency may itself
have been recruited by agency which specialises in recruiting agencies! A
system which, whilst it sounds hilarious, actually is not without certain
advantages.<BR><BR>Regards<BR><BR>Arthur<BR><BR>*challenging samples supplied
under CDAs by clients can be the basis for extending one's capabilities and
methodologies. OK - you cannot publish what you have done with a client's
sample. But a new approach which worked well CAN be applied to systems which
you are working on in a 'pure research' context. And then of course published.
Been there - done that. A.<BR></FONT><BR><BR></BLOCKQUOTE><BR>
<BLOCKQUOTE>Just though I would add a little to this thread:<BR><BR><FONT
color=#0000ff>(4) I agree with Arthur that to date most biotech companies have
not been terribly interested in reversible association thermodynamics. This is
probably going to change at least somewhat due to (3) above. <BR></FONT>I have
worked with a number of companies on drugs that interact with tubulin
and in each case I was allowed to pursue the full thermodynamic analysis of
the AUC data. It has a lot to do with how you sell it to them, who their
research director is, and how successful you are at convincing readers,
reviewers and the company the data has predictive value. Good data and
rigorous analysis is never a bad idea, even if companies are focused on their
bottom
line.<BR><BR><BR>-------------------------------------------------------------------<BR>Dr.
John J. "Jack" Correia<BR>Department of Biochemistry<BR>University of
Mississippi Medical Center<BR>2500 North State Street<BR>Jackson, MS
39216<BR>(601) 984-1522
<BR>fax
(601) 984-1501
<BR>email
address: jcorreia@biochem.umsmed.edu <BR>homepage
location: http://biochemistry.umc.edu/correia.html<BR>dept homepage location:
http://biochemistry.umc.edu/<BR>-------------------------------------------------------------------<BR><BR><BR><BR>Individuals
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