Kinase Chemistry – Just a year and a half behind the times.

PLX4032: burried in here?

Posted by kinasepro on January 8, 2007

So you know that kinase your working on. Yah, yah that one. Turns out that Plexxikon has compounds that inhibit it too. No, really. Between their two most recent applications to publish: WO/2007/002325, and WO/2007/002433 they claim <10 uM inhibition on no less then 36 kinases (+ n isoforms) with 22 authors. It’s an impressive body of matter, if pyrrolopyridines are your thing, and 1200+ pages of patent apps don’t scare you, check it out.


Don’t get too excited, like I say they only clam inhibition at < 10 uM

A lot of these compounds hit RAF and the stable of angiogenic kinases. Some of them might remind one of nexavar as diaryl ureas, but their leads actually have RAF cellular potency. They talked about the discovery of PLX4032 at the SF ACS meeting… but somehow I missed it ;( Still, without knowing anything else, I’m guessing the PLX4032 series is soundly buried in here somewhere. Seems possible the DNA thing is too.

One example doesn’t do these apps justice, where I say “R” I mean it in the most general sense.


WO/2007/002325, and WO/2007/002433

The examples in 25 are a hair more focussed, but both show quite a bit of diversity and I would be pretty surprised not to see a number of divisionals come out of these.

>> A side note >> From their homepage: “Scaffold-Based Drug Discovery™”

USPTO searches show no trademarks registered with that title to them or anybody else… Sloppy, but that page needs a little work anyhow… They did however abandon the “Scaffold discovery factory” trademark.

7 Responses to “PLX4032: burried in here?”

  1. milkshake said

    Analyzing such patent must be nightmare. But writing it is a good idea if you can get it through the patent referee. Not only writin a monster like this gives you a stronger patent protection on your compounds (especialy if you have some experimental examples demonstrating the concept and its scope) but it also burries the few good pieces under a pile of gravel so reverse-guessing SAR is hard. If any of your compunds eventualy make it into a clinical stage, you can allways follow up with a new and narrower patent application, for your best compound. That will buy you next few years on patent rights – in the same way as the Plavix patent lifetime was extended.

  2. weirdo said

    I don’t know about that line of reasoning. There are no more “CIPs”. Buying a few more years of patent life in this manner is no longer risk-free (if it ever was).

    These type of patent applications are being looked upon less and less favorably. And if major parts of the claims are rejected, you run the risk of losing what you really want. This type of application is better at muddying the waters for others, rather than clearing it up for yourself. It’s bad business, let alone bad science.

  3. milkshake said

    How do you risk getting your claims rejected – when you are disclosing that all your compounds have a new and unexpected activity below 5 mM for a panel of 20 kinases 🙂 Besides, if the referees turn you down, you can be a good boy and narrow your claims…

    The purpose of patent is not a good and original science – it is not a publication. Composition of matter patents are like a claim to real estate of molecules that includes a disclosure of your invention, description of the scope and representative examples. The examples should be representative of both the claims and the “best mode of invention” – except that you are not under obligation to tell which ones are actually the best ones.

    Look, I have seen companies claiming all kinds of stuff including structures of known natural products (which they cannot get, as a composition matter patents) and they got away with it. I guess somebody can challenge them in court and try to get the patent invalidated but not too many competitors are looking to a prolonged litigation. A big all-encopassing patent like this is a deterrent for others to even start working on similar stuff.

  4. kinasepro said

    $40M upfront from Roche suggests they’re fine, and you can bet a few Swiss laywers made sure of that before signing the deal, ;p. The only concern I’d have is on strength of some of the less exemplified matter. Its not like they’re the only ones making pyrrolopyridines as kinase inhibitors.

  5. weirdo said

    You guys clearly deal with a very different type of patent attorney than I do!

    Look, there is nothing surprising about azaindoles hitting a bunch of kinases. And getting your primary claims thrown out is never a good thing.

    The future of patent claims is more specificity and stronger cases. This seems to be going the other way. They seem to be risking the whole ball of wax. For what? Protecting azaindoles? Huh?

    “The purpose of patent is not a good and original science – it is not a publication. ”

    Actually, this is not a patent, it’s a patent application. And the only thing worth worrying about a patent application IS the publication. And getting the science wrong is a sure way to NOT get a patent granted. So you and I will need to respectively disagree on this point.

    Getting overly broad patents allowed is less and less common. Surely we can agree on that. And, after all, getting the key claims allowed is what it’s all about, isn’t it?

  6. Dennis France said

    Does anyone know whether the Plexxikon clinical candidate hits VEGFR2 (aka KDR) as hard as the Novartis/Chiron compound (CHIR265)?
    I think its an important feature because inhibition of this kinase has been linked to cardiovascular events (hypertension, stroke).

  7. nerdase said

    They published PLX4720 (a close sister of PLX4032) in PNAS ~1yr ago. It appearntly has little activity against KDR. PLX4032 could have different clinical profile comparing to sorafenib, chir265, & exel. An interesting B-Raf series is coming from Deciphera. nobody seems paying much attention except Lilly.

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