[RASMB] analysis of biotech samples [was: non-ideality in SV]

[John Philo]

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. 
 
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.
 
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.
 
John

  _____  

From: rasmb-bounces at rasmb.bbri.org [mailto:rasmb-bounces at rasmb.bbri.org] On
Behalf Of Arthur Rowe
Sent: Thursday, April 10, 2008 3:26 AM
To: John Correia
Cc: rasmb at server1.bbri.org
Subject: Re: [RASMB] analysis of biotech samples [was: non-ideality in SV]



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.

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.

Regards

Arthur

*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.





Just though I would add a little to this thread:

(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. 
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.


-------------------------------------------------------------------
Dr. John J. "Jack" Correia
Department of Biochemistry
University of Mississippi Medical Center
2500 North State Street
Jackson, MS  39216
(601) 984-1522                                 
fax (601) 984-1501                             
email address: jcorreia at biochem.umsmed.edu     
homepage location: http://biochemistry.umc.edu/correia.html
dept homepage location:    http://biochemistry.umc.edu/
-------------------------------------------------------------------



Individuals who have received this information in error or are not
authorized to receive it must promptly return or dispose of the information
and notify the sender. Those individuals are hereby notified that they are
strictly prohibited from reviewing, forwarding, printing, copying,
distributing or using this information in any way. 
_______________________________________________
RASMB mailing list
RASMB at rasmb.bbri.org
http://rasmb.bbri.org/mailman/listinfo/rasmb







This message has been checked for viruses but the contents of an attachment
may still contain software viruses, which could damage your computer system:
you are advised to perform your own checks. Email communications with the
University of Nottingham may be monitored as permitted by UK legislation. 

-------------- next part --------------
An HTML attachment was scrubbed...
URL: <http://list.rasmb.org/pipermail/rasmb-rasmb.org/attachments/20080410/b6f49952/attachment.htm>