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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: Twitter: Dereklowe

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May 16, 2004

Owning the Road

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Posted by Derek

I mentioned method-of-treatment patents last week, and it's time for me to come back to the topic. These aren't what people think of as "use patents" - the sort of thing you'd apply for when you discover a new use for a known compound. No, method-of-treatment patents seek to own an entire biochemical pathway, and to collect a fee from every drug that might use it.

A fine example of the breed is attempt by a small biotech, Ariad, to exert rights to the NF-kappa-B signaling pathway. (I wrote about this on my old Lagniappe site more than once, and the legal maneuverings are still far from complete.) Ariad is the sole licensee to a patent obtained by the discoverers of this protein, a patent that enumerates, in horrible detail, its two hundred and threeclaims to everything having to do in any way with anything that so much as touches NF-kappa-B and any of its myriad signaling pathways. You have to see it to believe it. The claims are a relentless paving machine, spreading hot asphalt on everything in sight and spraying lane markers for the toll booths. Here's a PDF of Ariad's side of the story, if you'd like it.

Ariad's fired legal shots at several dozen companies, but their lawsuit with Eli Lilly will be the real test. Lilly's sepsis drug, Xigris, works through NF-kB, as does damn near everything else that has to do with inflammation. And their osteoporosis drug, Evista, works through it too, as does damn near everything else that involves signaling through the estrogen receptor. Bristol-Meyers Squibb has already rolled over and paid Ariad, which I have to say seems rather spineless of them, but most other companies have either stalled or told Ariad to take a hike. Needless to say, everyone will be watching the Lilly case with great interest.

I don't know if the case will be fundamental enough to answer the real question, though: should such patents even exist? Not every patent office will grant this sort of thing, although the US PTO sure will. I know what I think: there just seems to be something wrong about being able to set up a turnstile and coin box on a fundamental biochemical pathway.

Now, I know that people patent enzymes, and I know that companies have all sorts of proprietary cells and enzyme systems that they sell. Hey, look at PCR. But what gets me about patents like Ariad's is that they seem to cast too large a shadow. We own the pathway, because we found it first. Does your drug touch it? Too bad - pay up. Didn't know that it did? Not our problem. Not its primary mode of action? Not our problem. You say that you did all the work on your drug yourself and you don't see why you should pay us? Time to read those two hundred and three claims more closely, bub.

The parallels between this and the University of Rochester's fight over COX-2 inhibitors are interesting. Rochester lost the latest round, because the court held that their claim to inhibitors of COX-2 wasn't valid. They hadn't made one, and had no idea of how to make one, but they claimed any inhibitor from anywhere because it touched the magic enzyme. No dice. Will this reasoning gut Ariad's claims?

As you can probably tell, I damn well hope so. I know that there are other companies playing the same game, but I wish none of us were. We're going to cut our own throats by trying to cut everybody else's, if we're not careful. I'm a big fan of patent protection, but I have my limits. I'd like robust protection, sure, but for real objects that do real things. (And yes, this means that I hold business-method patents in contempt, too.) However, I know from my last time writing on this subject that not everyone agrees with me on this, so I'm bracing for a round of comments and e-mail. Good luck convincing me, though.

Comments (6) + TrackBacks (0) | Category: Patents and IP


1. Nick Henriquez on May 17, 2004 4:05 AM writes...

It's quite simple really. Did the applicant find something NEW and not-obvious?

This applicant found (not invented) NFkB and various functions. From thos functions stem a number of OBVIOUS applications. These should not be patentable. Not even in the US.

And yes, this includes patents for cancer genes should not be patentable as a method ofr cancer testing. Anyone that invents a particular WAY of testing for the enzyme could make a good case in my view. Anyone using a different way of doing it should not be affected.

So company X which makes antibody Y to test for gene expression may patent "testing for expression using this antibody". Most rules allow "using this epitope" so we I guess democratically we should allow that. But not "this is the DNA sequence, everything stemming from it is mine, mine, mine...." (diabolical laughing in the background).

Someone commented a while ago that "the patent rules are simple". I would actually agree. The mess that various IP offices make of them isn't and those methods should be ditched (not patented).

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2. qetzal on May 17, 2004 10:02 AM writes...

I agree that method of treatment patents seem to cast too large a shadow, as you nicely put it. But I also think it's hard to articulate why MOT's are fundamentally different than other classes of patents.

For example. Suppose I discover a new biochemical pathway that plays a fundamental and previously unanticipated role in breast cancer. Furthermore, I demonstrate that inhibiting a key protein in that pathway offers dramatic therapeutic benefit. Finally, assume I come up with 2-3 different inhibitors, and show that they work as I claim. To make an even stronger case, let's assume that most scientists would not have recognized the connection between this pathway and breast cancer, even had they discovered the pathway before me.

So naturally, I submit an application for a method of treatment patent, claiming anything that treats breast cancer through "my" newly discovered pathway. (Of course, I also submit composition of matter &/or method of use patents for the specific inhibitors, but that's beside the point.)

How is the MOT any less new, useful, and non-obvious than a method of use patent, or a process patent? By definition, the pathway is new, and so is the demonstration that inhibiting the key protein has therapeutic benefit. Utility is also clear. And it seems pretty non-obvious. So, why should it not qualify for a patent?

One could argue that I didn't invent the pathway or its role in breast cancer, I only discovered it, and so it shouldn't qualify for a patent. But the same argument could be used against method of use patents. If I show that a known compound has a previously unrecognized activity, I didn't magically bestow that activity on the compound. I simply discovered a pre-existing activity that others had missed. So why should that be fundamentally patentable, but MOT's shouldn't?

In the end, I'm left feeling that MOT's are somehow fundamentally different, but I can't come up with a satisfying objective distinction. Still, I do think that MOT's go too far. Maybe the answer is to go back to the standard justification that patents are meant to be a sort of balancing act. The inventor gets some limited monopoly power, which promotes invention, commercialization, disclosure, and societal benefit. And the limits to that monopoly power are theoretically set so as to maximize overall benefit. Obviously, judging where to set those limits is highly subjective, but I think that MOT's go too far, and result in a net societal detriment.

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3. Eric Towers on May 17, 2004 12:24 PM writes...

Observations about MoT patent subjects relative to common patent rubrics and simplifications:

Are not a "functional expression of an idea". They might be copyrightable, but the prior art is rather substantial given that everyone's been implicitly copying it for thousands of years.

Are not "[anything under the sun] made by the hand of man". I can discover a mountain; this does not mean I "made" it. So, should I be able to patent every method of observing or passing this mountain?

Are not "new" (of "new and useful") since again people have been implicitly performing the method for thousands of years.

Of "nonbvious and reproducible by one skilled in the art", "nonobvious" might hold. Reproducibility is outside the scope of anyone's skill -- i.e. how can I make *another instance of this pathway*?

A pathway represents a sequence of processing steps carrie dout by a machine. It is therefore an algorithm. Algorithms are not patentable until reduced to (tangible) practical application. Thus, one could patent particular implementations of the pathway, but not the abstract pathway itself.

However, under the rubric that IP is anything that provides a competitive advantage, it's not clear that a MoT patent is IP. Yes, the applicant has done the science to identify and map the pathway, but it doesn't provide competitive advantage until a method for implementing or utilizing the pathway is created. It's not clear that elucidation of the pathway produces a competitive advantage in that creation. There's still considerable trial and error to find something that works "all the way through" -- the same trial and error that would be required without elucidation of the pathway.

So, MoT patents seem to fail on many levels as being IP or patentable. But that's never really stopped the USPTO.

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4. Chris C on May 17, 2004 5:59 PM writes...

Hear, hear! The companies and institutions that try to exploit these specious patents sully the good name of science and make us all into the intellectual equivalent of con-men, hustlers, and pimps.

It is obvious that we cannot rely on the moral compass of bureaucrats and lawyers to get us out of this mess. It is up to us as researchers to call on our training in intellectual honesty and integrity to put an end to the madness.

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5. Daniel Newby on May 17, 2004 6:32 PM writes...

How does prior art apply to these patents? It would seem that any preexisting drug or treatement that modulated the pathway would invalidate it. Even if it wasn't recognized at the time. Even if the drug was rejected for toxicity in 1870. That's an awfully big minefield to go staking a claim in.

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6. qetzal on May 17, 2004 8:53 PM writes...

Eric, you're missing the point. MoT doesn't patent the pathway, it patents a method of treatment involving *modulating* the pathway.

Again, I'm against MoT's, but I'll play devil's advocate.

Why isn't an MoT a "functional expression of an idea?" I discover the pathway, come up with the idea of modulating it with a drug, find such a drug and show that it a) does in fact modulate the pathway, and b) lead to a useful outcome. Idea, expression, function.

"Made by the hand of man." True, I did not make the pathway. But did I not "make" the idea of modulating it, through administration of some drug molecule, to have a useful effect? If not, please explain how that is different than "making" the idea of using a known drug in a new application (i.e. a method of use patent).

Not new? The pathway isn't new, of course, but the idea of modulating it with a given drug is.

Reproducible - again, it's not the pathway that's being patented, it's the method of treatment based on the pathway. No reason that can't be reproducible.

As for the trial and error required to make something that works all the way through, sure - if the applicant hasn't done that one can argue to reject on that basis. That's the COX-2 example that Derek cited. But what if the applicant has *already* come up with something that works as predicted? Or several somethings? If s/he shows that multiple compounds modulate the pathway, and all have the desired effect, that would be pretty strong evidence that the MoT really does work.

So, I still don't see a good argument for *why* MoT's shouldn't be allowed, except to say that they're too broad and ultimately bad for society as a whole.

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