Corante

About this Author
DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

Chemistry and Drug Data: Drugbank
Emolecules
ChemSpider
Chempedia Lab
Synthetic Pages
Organic Chemistry Portal
PubChem
Not Voodoo
DailyMed
Druglib
Clinicaltrials.gov

Chemistry and Pharma Blogs:
Org Prep Daily
The Haystack
Kilomentor
A New Merck, Reviewed
Liberal Arts Chemistry
Electron Pusher
All Things Metathesis
C&E News Blogs
Chemiotics II
Chemical Space
Noel O'Blog
In Vivo Blog
Terra Sigilatta
BBSRC/Douglas Kell
ChemBark
Realizations in Biostatistics
Chemjobber
Pharmalot
ChemSpider Blog
Pharmagossip
Med-Chemist
Organic Chem - Education & Industry
Pharma Strategy Blog
No Name No Slogan
Practical Fragments
SimBioSys
The Curious Wavefunction
Natural Product Man
Fragment Literature
Chemistry World Blog
Synthetic Nature
Chemistry Blog
Synthesizing Ideas
Business|Bytes|Genes|Molecules
Eye on FDA
Chemical Forums
Depth-First
Symyx Blog
Sceptical Chymist
Lamentations on Chemistry
Computational Organic Chemistry
Mining Drugs
Henry Rzepa


Science Blogs and News:
Bad Science
The Loom
Uncertain Principles
Fierce Biotech
Blogs for Industry
Omics! Omics!
Young Female Scientist
Notional Slurry
Nobel Intent
SciTech Daily
Science Blog
FuturePundit
Aetiology
Gene Expression (I)
Gene Expression (II)
Sciencebase
Pharyngula
Adventures in Ethics and Science
Transterrestrial Musings
Slashdot Science
Cosmic Variance
Biology News Net


Medical Blogs
DB's Medical Rants
Science-Based Medicine
GruntDoc
Respectful Insolence
Diabetes Mine


Economics and Business
Marginal Revolution
The Volokh Conspiracy
Knowledge Problem


Politics / Current Events
Virginia Postrel
Instapundit
Belmont Club
Mickey Kaus


Belles Lettres
Uncouth Reflections
Arts and Letters Daily
In the Pipeline: Don't miss Derek Lowe's excellent commentary on drug discovery and the pharma industry in general at In the Pipeline

In the Pipeline

« How Not to Do It: Solvent Stills | Main | The Patent Expiration Fun Continues »

September 2, 2002

A Last-Ditch Effort - Or Is It?

Email This Entry

Posted by Derek

There's a rather weird legal fight going on between Glaxo SmithKline and the rest of the world. Like everyone else, GSK is fighting to hold on to profitable drugs that are losing patent protection. A lot of. . .creative. . .arguments are being deployed in these efforts, and I can't figure out if this is one of them or not.

The drug is Augmentin, which is actually two drugs in one. (For those readers old enough to remember it, you can now cue up the voice-over to the old Certs ad.) The antibiotic ingredient is plain old amoxicillin, a beta-lactam warhorse that's been generic for a long time now. Unfortunately, plenty of bacteria can chew right through amoxicillin and others of that era. I mean that literally: they use an enzyme called beta-lactamase to break open the four-membered ring at the core of all the penicillins.

That's where the second ingredient comes in, clavulinic acid (actually, its potassium salt.) It's a natural product that has a roughly similar structure, similar enough to fit into the active site of the beta-lactamase enzyme and gum up the works. Using the enzyme inhibitor leaves the amoxicillin free to do its work, and the combination is quite effective.

Well, amoxicillin you can order by the drum. But clavulinic acid is another matter. It's not economical to synthesize, not from the ground up (and neither are the beta-lactam antibiotics themselves, for that matter.) All these compounds are made (at least partially) by fermentation, which is just short of being a black art. You have to find strains of organisms (fungi for the 'cillins, bacteria for clavulinate) that produce unusually high amounts of the material, and you have to make them do it reproducibly. That means keeping them happy, but not so happy that they decide to give up the hard biochemical work of synthesizing your compound. And you have to find a good way to purify your stuff from the reeking fermentation broth - ideally in a continuous-feed mode so you don't have to run batch after batch. It's not trivial.

Perhaps you can guess where this is heading. GSK claims that they spent a lot of time and money developing a particular bacterial strain that produced clavulinic acid better than anything else known. And they're now claiming that some of these bacteria walked out of their facilities and are being used by their competitors (specifically Novartis as well as the generic companies Ranbaxy and Teva.) They seem to have a particular employee in mind, and a particular transaction history for the theft.

Problem is, that all happened starting in 1988. You wonder why GSK sat back for this long if they knew all this. . .and there are generic Augmentin formulations in Europe which don't figure into the suit. How'd they make their clavulinic acid? You do have to wonder if this isn't a desperation move.

On the other hand, this sort of theft isn't unknown. About twelve years ago, a New Jersey drug company had a former employee walk out with some of their engineered bacteria, which he later tried to sell to at least one small biotech outfit. They went to the Feds. The employee was caught on tape, thinking that he was selling the material to a Middle Eastern government, when he was really selling it to the FBI on two camera angles.

So GSK could be on to something, too. It'll be fun to watch.

Comments (0) + TrackBacks (0) | Category: Infectious Diseases | Patents and IP


COMMENTS

EMAIL THIS ENTRY TO A FRIEND

Email this entry to:

Your email address:

Message (optional):




RELATED ENTRIES
Days Off
Shuffling the Departments
Funding Undergraduate Summer Research
J. Appl. Drivel or Gibberish Lett.? Choices, Choices.
Molecular Printing of Drug Molecules. Say What?
Pfizer Walks Again By Night
Gitcher SF5 Groups Right Here
Changing A Broken Science System