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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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In the Pipeline

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December 12, 2011

Don't Dose That Patient Until You Pay Up

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Posted by Derek

Now here is an awful, awful idea, and it's made it all the way to the Supreme Court. Oral arguments were heard last week in Mayo Collaborative Services v. Prometheus Laboratories, and this one really has the potential to screw things up.

Why am I so downbeat? Wait until you hear the basis of this case. Prometheus has a patent whose first claim is as follows:

(1) A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising:

(a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and

(b) determining the level of 6-thioguanine in said subject having said immune-mediated gastrointestinal disorder, wherein the level of 6-thioguanine less than about 230 pmol per 8x10^8 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject and wherein the level of 6-thioguanine greater than about 400 pmol per 8x10^8 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.

There, that sounds like a nice little chunk of medico-legal boilerplate. But look closely: what they're claiming is the process of using a blood test to decide whether or not to administer a drug. Prometheus Labs did not discovery any immune-mediated gastrointestinal diseases. They most certainly did not discover thioguanine, nor did they discover that giving thioguanine is beneficial to people who are deficient in it. No, they make a test kit, and they are claiming the process of checking a patient's blood levels (their test kit's function) in order to make a medical decision. The Mayo Clinic planned to offer a competing test kit, and Prometheus sued, and here we are.

Now, think about a world in which such processes are patentable (here's a column at Ars Technica that's done that already). Prometheus seems to be claiming that the awareness of needing to test for thiopurine levels in order to decide whether to dose a patient is enough to infringe their patent. Doesn't matter if the physician doses anyone or not - just the idea of testing their blood is enough. IP rights have been infringed. Money must change hands. Ka-ching. Imagine every new bit of medical practice broken down into the smallest patentable, monetizable steps. A physician reads about a new finding that might affect clinical practice - but not so fast! Better check to see what the patent rights are. Wouldn't want to get sued for applying the scientific literature without the proper licensing fees. As the AMA's amicus brief has it:

"If claims to exclusive rights over the body’s natural responses to illness and medical treatment are permitted to stand, the result will be a vast thicket of exclusive rights over the use of critical scientific data that must remain widely available if physicians are to provide sound medical care"

If you follow intellectual property issues, you'll have noted the similarity of this case to software and business-method patents, which have been a gigantic tar pit of litigation for some years now. But the tide of tar is not finished rising. The IP lawyers are, as you'd expect, watching this case with great interest, some with thoughts of perpetual employment, and some in a sort of fascinated horror. This problem has been developing for a long time, since the main legal decisions on what constitutes patentable matter actually appear to contradict each other, and perhaps this will be the case that begins the ugly process of sorting all that out. (Or perhaps the Supreme Court will recoil from that task and decide this case on some narrower basis, kicking the issue a few years into the future).

Here's a more technical legal summary of the oral arguments at the Patently-O site. It appears that Justice Breyer will be a key player in the eventual opinion; he spent by far the most amount of time asking questions during the orals. And here (also from Patently-O) is a new law review paper from Case Western on the whole tangled subject of medical diagnostic patents. This post at Patent Baristas has links to the various briefs filed on both sides of the case.

Comments (17) + TrackBacks (0) | Category: Patents and IP


COMMENTS

1. Jonathan on December 12, 2011 9:48 AM writes...

Let me state up front that I don't believe these kinds of patents are healthy, or that they meet sections 101, 102, or 103 of the Patent Code.

That said, they've been with us for a while now. The Supreme Court declined to hear a similar case between LabCorp and Metabolite on correlating homocysteine levels with vitamin B6 and B12, and the Federal Circuit (a court created to mainly deal with patent litigation) seems more than happy to allow these sorts of things, to the point where the chief judge of that court, Judge Rader, basically came out and told the community to stop even challenging these things as "laws of nature or abstract ideas": http://www.genomicslawreport.com/index.php/2011/09/14/classen-has-the-federal-circuit-lost-interest-in-patentable-subject-matter/

What's more, surgical procedures have been patentable since the 1990s, despite an uproar from the AMA et al. That fuss actually resulted to a change in the law, but not to exclude such patents, merely to give MDs immunity from prosecution from infringing them.

The federal circuit might have knocked down the genotype-phenotype correlation patents in the Myriad case but only on a tiny technicality that a subtly rewritten claim would avoid.

Perhaps just reading the SCOTUS transcript fails to convey the nuances of their questions; all I know is after reading it, I have absolutely no confidence that the Supreme Court has anywhere near the understanding of the subject matter needed to be able to properly judge this case. They scramble for poor analogy after poor analogy, and it's quite worrying.

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2. Cellbio on December 12, 2011 10:24 AM writes...

I don't like this sort of patent either, but do you read it correctly, maybe I have it wrong? Seems like it requires both administering a dose and measuring blood levels to adjust future doses. Small point I guess.

It is a real challenge for diagnostic companies to protect their markets, and this is one effort to protect use of their test by barring entry of a competitor (wonder if there are other claims with more substance). It is not too dissimilar from use claims that accompany therapeutics. Even in cases where there are strong composition of matter claims, use claims, manufacturing claims and other reaches are used to protect the space. Yes it is a problem, but having megamillions spent to reach into established well served markets is also a problem, especially when the competing products offer no cost benefit. In this case, I wonder if Mayo is trying to offer the same benefit at reduced cost.

My favorite claim, for a competitor we beat to composition of matter on a biologic, was: 'a glass vial containing the drug'. Merely trying to be a menace and have an angle to future payout if the drug hits big. In addition to the problem with the courts having enough expertise, we also need examiners that prevent the claims from issuing in the first place.

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3. Acleron on December 12, 2011 10:48 AM writes...

Have the rules on obviousness now been changed? This is bleedin obvious.

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4. milkshake on December 12, 2011 10:50 AM writes...

this claim is ridiculous: its like a medical device company that develops their own version o EKG instrument to monitor treatment of heat condition, files broad method patents on it - and then sues their competitors and the physicians, for making and using any competing EKGs for monitoring treatment of heart diseases

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5. Student on December 12, 2011 10:59 AM writes...

Beyond FDA approval, is there much incentive for one (the drug owning company) to find better tests to administer their drug? If this incentive isn't great, I feel like it is "menial" enough for academic labs to pursue. With budget cuts and increased competitiveness for original grants will that get accomplished? How much money goes into unraveling a dosing protocol that wasn't previously established?

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6. Cellbio on December 12, 2011 11:48 AM writes...

@5

If I understand your question, companion diagnostics aiming at defining who would benefit from a therapy have financial incentives that are often not aligned, meaning what may be good for the payor may not be good for the drug company, and depending on whether the test is reimbursed, the patient may come out of pocket. The test provider is squeezed in between, bounding test costs (must be less than drug costs, both therapy and associated adverse events, across the population for the time interval to know it failed). What I think is potentially interesting about Mayo, is it looks to me like a model where the institution is aiming to offer tests, drug level and genetic, developed in their own labs, instead of buying from external providers. If true, would bring the financial incentives more into alignment and lessen the influence of profit motives.

Both Deloitte and McKinsey published good papers a few years back about this issue, worth reading.

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7. NoDrugsNoJobs on December 12, 2011 11:52 AM writes...

Not all pharmaceutical inventions are compounds. The reality is that diagnostics are extremely important and without IP protection, many companies will avoid the space and believe me, we won't have the kind of tests we do now. The claim covers a method of treating that includes a method of diagnosis based on that treatment to avoid side effects. I see a particular range of metabolite covered and am not sure how this is different than testing for a genetic variant to improve treatment. The actual determination of the blood levels is trivial but the invention putatively lies in the discovery that the metabolites cause the side effect and do so outside a certain range. There is a whole world of pharmaceutical research and discovery outside making and testing new compounds and patent law should/will reflect that.

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8. Vader on December 12, 2011 12:48 PM writes...

My guess is that SCOTUS will decide the case on the much narrower issue of whether doing a blood test to see if the dosing is right is sufficiently non-obvious to be patentable. To me it seems obvious that it is not.

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9. Sigivald on December 12, 2011 2:21 PM writes...

I could imagine a process patent being valid, if it were actually thoroughly novel.

How this could stand a prior art or obviousness challenge is beyond me...

(As NoDrugs says above, a novel method of diagnosis might be both expensive to develop and, well, novel - combine those two and a patent seems fair.

The ridiculous thing here is that nothing in this case seems particularly novel - and adding "providing 6-thioguanine" does not change that.*)

(* I'm a software developer for a point-of-sale system, and we joke about patenting "obvious-thing-eveyone-has-done-for-years 'in a point of sale environment'" to make fun of exactly this sort of shenanigan.)

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10. johnnyboy on December 12, 2011 2:47 PM writes...

I just jotted down on a bit of napkin a new patent application - it's a great idea I just had, about checking blood glucose level to adjust insulin dose. Off to the patent office now - gonna make a killing !

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11. patentgeek on December 12, 2011 3:59 PM writes...

One thing notable in J. Breyers' comments is that he appears to be rethinking his position on patent-eligible subject matter expressed in his Labcorp dissent ( Laboratory Corp. of Am. Holdings v. Metabolite Labs Inc., 548 U.S. 124 (2006)). Since Mayo relied on this position, it may bode ill for them. Detailed discussion at patents4life.com for those interested.

As many posters noted, the claims may be vulnerable on grounds of obviousness, perhaps anticipation. (103, 102). Why were they challenged under 101? Rader's "Additional Views" in the Classen case, noted by Jonathan, make it pretty clear that challengers who continue to use 101-ineligibility as their argument for invalidity do so at their peril.

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12. cliffintokyo on December 12, 2011 7:24 PM writes...

"Fascinated horror" says it all really.
Excellent post.

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13. Patent Chemist on December 12, 2011 11:30 PM writes...

The issue the Supreme Court is considering is whether the claim (directed to administering an artificial drug, testing for metabolite levels and adjusting the dose based on the testing) should be patent eligible subject matter under section 101.

Mayo is arguing that it shouldn't be allowed because it is some sort of "natural process". That is nonsense. The drug is an artificial drug.

Under the patent law, whether the claims are novel or obvious is a separate issue. The danger with this case is that the Supreme Court will find the claim not to be patentable subject matter. That could be interpreted broadly to disallow patents to all sorts of diagnostic and method of treatment claims. That would not be good for the pharma industry.

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14. Morten G on December 13, 2011 8:01 AM writes...

This isn't that different from a Swiss-type claim though, is it? Not the actual legalese of Swiss-type but the intent behind it.

On the other hand it is a bit like trying to patent pharmaceutical modulation of protein x to treat disease y.

Couldn't Mayo Collaborative Services just market their test for non-"immune-mediated gastrointestinal disorder" uses? Or measure a metabolite of tioguanine?

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15. Patentingnstuff on December 13, 2011 12:41 PM writes...

Derek, Sorry, you're confused. If this were in the literature, it wouldn't be patentable for novelty reasons. Nothing to do with patentable subject matter here. To be fair, Mayo is confused, too. Their real point seems to be that they invented an improvement and want to sell it, but can't (not without paying up)because of Prometheus. Boo hoo. I usually hesitate to predict what the Court will do, but her I think Mayo loses at least 7-2 because their arguments are naive and overreaching. I suspect some big egos at Mayo are involved because their legal strategy seems designed to appease the client rather than to win or facilitate any sort of business concerns.

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16. John Harrold on December 14, 2011 4:25 PM writes...

It sounds like they are patenting negative feedback control. There should be plenty of prior art in the systems engineering literature (also called textbooks).

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17. pete on March 21, 2012 12:08 PM writes...

@13 Patent Chemist
If the patent claims here are disallowed, I don't see how that would have such a widespread, blanket negative effect on patenting new diagnostics. Aren't new diagnostics patent applications already subject to the "machine-or-transformation" test ? So wouldn't a negative decision here just serve to raise the bar against diagnostics that are based on methods -- methods that might seem obvious to others ? Interested to hear your thoughts, thanks.

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