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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

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« Let's Hope They're Right | Main | A Brief and Not At All Intemperate Evaluation of the Current Literature »

April 6, 2010

Take These?

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Posted by Derek

A reader sends along a note about this patent application from the University of Rochester. The inventor, David Goldfarb, seems to have used an assay (the subject of a previous application) to screen a library of commercially available compounds for potential life-extending properties in model organisms. Here's some detail on the screen from PubChem.

The abstract of the application makes it sound worse than it is: "A method for altering the lifespan of a eukaryotic organism. The method comprises the steps of providing a lifespan altering compound, and administering an effective amount of the compound to a eukaryotic organism, such that the lifespan of the organism is altered. . ." That sounds like one of those "Oh, get real" applications that the patent databases are cluttered with. But when you get to the claims, you find that a list of compounds is specifically given, with more- and most-preferred ones as you go down. And I don't have a problem with that, as far as it goes - the inventor has an assay, has run a bunch of compounds through it, and finds that some of them have utility that apparently no one else has recognized.

The compounds themselves, though. . .well, here are the specifically claimed ones on the list. I don't necessarily see aliphatic triketones extending my life, but perhaps I'm cynical.

Comments (18) + TrackBacks (0) | Category: Aging and Lifespan | Drug Assays | Patents and IP


COMMENTS

1. mikeymedchem on April 6, 2010 11:03 AM writes...

well THERE'S some SAR.

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2. Anonymous on April 6, 2010 11:06 AM writes...

"I don't necessarily see aliphatic triketones extending my life, but perhaps I'm cynical."

Well, cynical or not I'm with you!

-Indy.

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3. anonymous2 on April 6, 2010 11:12 AM writes...

I hope it did not escape you that the broadest claim did not claim "extending" lifespan, merely "altering" it. I would have thought lifespan-altering compounds had been around awhile, at least since Socrates drank his potion.

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4. weirdo on April 6, 2010 11:26 AM writes...

What do you have against the University of Rochester? You clearly just hate the fine scientists there who do nothing but commit themselves to helping others. You always have; you're clearly biased. That's how you got those stupid judges to rule against Ariad.

Out! Out! Evil!

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5. Sili on April 6, 2010 11:32 AM writes...

Any FOOF?

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6. Chris on April 6, 2010 11:32 AM writes...

The aliphatic tricarbonyl shown in Derek's link is almost certainly in the ring enolic form. That would make it a very nice Michael substrate with a push pull polarized double bond. I independently came upon this patent when I was following up on some of the compounds identified in the PAINS promiscuous hits paper. If you look at the compounds with the best claimed activity in the patent they have something in common. They are commercially available with CAS registry numbers and no literature references. I think many (most) are very likely flawed compounds that light up HTS assays and therefore proliferate in vendor libraries. When they show up in the literature it is in patents like this one.

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7. sgcox on April 6, 2010 11:42 AM writes...

Well, the very first figure in patent shows Sir2 activation... The guy is obviously after GSK money and why not, it is a l validated target. ;)

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8. Eraser on April 6, 2010 12:39 PM writes...

Uh isnt FK506 nearly that (its a diketoamide with one ketone in hemiacetal form)

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9. alig on April 6, 2010 1:35 PM writes...

That patent is annoying. It has no chemistry, but substructure searches pull back that reference all too often. What a waste of money and time to file that monster.

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10. milkshake on April 6, 2010 3:14 PM writes...

Nature makes ugly dicarbonyl compounds too - compounds that are highly bioactive, i. e. tetramic acids. You need to test the lifespan-extending effect in a whole organism assay. Then if you get something that has a nontrivial effect one ought to do some quick SAR optimization to get more potent compound, then one should probably try look for the actual target.
If they want to use these initial leads just as a probe (and not a drug) for finding new lifespan-extending targets I say more power to them.

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11. anon on April 6, 2010 3:40 PM writes...

All those worthless filings; the dude will be out of grant money to support grad students! I guess if he grabs the GSK ring, as sgcox suggested, he won't need to!

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12. milkshake on April 6, 2010 4:14 PM writes...

From what I heard the initial stages to get a patent application is quite affordable, it only gets expensive few years later, once you get your WO patent approved and it moves to the stage where you do a whole bunch of national filings. I think this will not happen in this case.

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13. Jonathan on April 6, 2010 5:25 PM writes...

Like alig, I find that almost any search on a screening hit - the good, the bad, and the ugly - returns this useless patent in the SciFinder answer set and it is frequently broken up into many separate reference hits. It is distracting, time-wasting and resource consuming and indirectly taints what may be reasonable screening hits because they are listed (if not claimed) in that patent along with all the dodgey ones.

If anyone knows of a way to get SciFinder to de-list such references, please let me know....or let SciFinder know.

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14. milkshake on April 6, 2010 5:37 PM writes...

#13: if you search a reactions in Scifinder and do not wish for a 10-step reaction appear 9 times, you just specify the number of reaction steps in your process - there is a field for that in the search window. I always search for one step reaction schemes, then again for two-step just to be I did not miss something

(I still like Beilstein/Crossfire rearches better)

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15. Will on April 7, 2010 7:50 AM writes...

Milkshake is right - the strategy for the inventor is not necessarily to take the application to granted patent, but rather have all his IP-ducks in a row while he or his tech transfer office are out soliciting companies to buy/license the technology.

From his Dec. 2007 provisional date, he's probably got another year at least before the application receives its first action - that's 3+ years to find a partner.

For those that care, here are the relevant filing fees for this application:

provisional application fee (small entity) 2x $105 = $210

regular app fee $75 or $155 depending on how filed

search and examination fees $155 and $105.

Assuming they didn't pay an attorney to draft the application - the total cost is ~$700, not too much

I can't imagine the attorney time needed to respond to (and overcome!) the rejections that this application deserves, quite a bit I would imagine

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16. mikeymedchem on April 7, 2010 7:57 AM writes...

This underscores something that irks me. As an industry-to-academia transplant, I am often critiqued for having few med chem publications (I worked in hit-to-lead...and there were few opportunities to publish). Then, I often get the response "well, then you should have more patents...". As if (1) an industrial scientist gets to choose when and what s/he patents, and (2) you couldn't just patent garbage (since, obviously, no peer review).

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17. virgil on April 7, 2010 8:26 AM writes...

I know this guy, and the real "inventive step" here is the assay itself, i.e. the design of the screen. Clearly, he's aware of the issue that whenever you do a screen you're limited by what you shove in the front end. As has been mentioned several times on this blog, commercial libraries are littered with failed compounds. What the patent is really after, is to find a partner with a much bigger library containing more druggable molecules, to run the proprietary screen on.

In addition, as "lifespan extending" strategies go, there really isn't that much out there that works in all models. Antioxidants are a huge bust. Porphyrins and other enzyme mimetics are toxic as all get out in large animals. Caloric restriction is the only thing that works in every model tested so far. Thus, a screen that seeks to find molecules that mimic CR is not actually that bad of a starting point! The screen is really about finding things that overcome nicotinamide inhibition - back when they did the screen clearly the thought was that the target was SIRTs. However, even if it is not working via SIRT, there are a ton of NAD dependent enzymes involved in oxidative stress and metabolic responses, so who cares if the molecules are working via those mechanisms and not SIRT? All that really matters is he's found something that extends lifespan in yeast, and it is a relatively simple step from there to scale it up into mammals and do the SAR to make druggable molecules.

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18. Cellbio on April 7, 2010 11:21 AM writes...

Wow, really? It is simple to "scale up" biology to mammals?

I've got a brilliant idea...let's run tumor models, arthritis models, lupus models, AD models etc in rodents so we jump start the mammal scale up, then rapidly progress to curing human suffering. Should expunge human disease in a few months. I'll get back to you soon, got work to do.

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