Prometheus Diagnostic Methods Are Patentable Subject Matter

On Friday, December 17, 2010, the United States Court of Appeals for the Federal Circuit issued a decision in one of the patentable subject matter cases that was returned to the Court by the Supreme Court in the wake of the Supreme Court’s decision in Bilski v. Kappos. Prometheus Laboratories, Inc. v. Mayo Collaborative Services first reached the Federal Circuit on an appeal brought by Prometheus, challenging the final judgment of the United States District Court for the Southern District of California. The district court had granted summary judgment of invalidity of U.S. Patents 6,355,623 and 6,680,302 under 35 U.S.C. § 101. In the original case the Federal Circuit held that the district court erred as a matter of law in finding Prometheus’s asserted medical treatment claims to be drawn to non-statutory subject matter under the machine-or-transformation test, which at the time was the definitive test for determining the patent eligibility of a process under § 101. In Bilski, however, the Supreme Court held that the machine-or-transformation test, although “a useful and important clue,” was not the sole test for determining the patent eligibility of process claims. The Supreme Court vacated and remanded the Prometheus case for further consideration in light of Bilski v. Kappos. On remand, once again, the Federal Circuit held (per Judge Lourie with Chief Judge Rader and Judge Bryson) that Prometheus’s asserted method claims are drawn to statutory subject matter, reversing for the second time the district court’s grant of summary judgment of invalidity under § 101.

Prometheus is the sole and exclusive licensee of the ’623 and ’302 patents, which claim methods for determining the optimal dosage of thiopurine drugs used to treat gastrointestinal and non-gastrointestinal autoimmune diseases. Although drugs incorporated into the patent have been used for years to treat autoimmune diseases, non-responsiveness and drug toxicity may complicate treatment in some patients. Thus, the focus of the patents claims were methods that optimize therapeutic efficacy while minimizing toxic side effects.

Claim 1 of the ’623 patent, which is representative of the independent claims asserted by Prometheus in this case, reads:

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 8×10⁸ 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 8×10⁸ red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.

(emphases added by the Federal Circuit in its decision). Claim 1 of the ’302 patent is substantially the same.

Claim 46 of the ’623 patent dispenses with the “administering” step and claims only the “determining” step:

46.  A method of optimizing therapeutic efficacy and reducing toxicity associated with treatment of an immune-mediated gastrointestinal disorder, comprising:

(a) determining the level of 6-thioguanine or 6-methylmercaptopurine in a subject administered a drug selected from the group consisting of 6-mercaptopurine, azathiop[u]rine, 6-thioguanine, and 6-methyl-mercaptoriboside, said subject having said immune-mediated gastrointestinal disorder,

wherein the level of 6-thioguanine less than about 230 pmol per 8×10⁸ 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 8×10⁸ red blood cells or a level of 6-methylmercaptopurine greater than about 7000 pmol per 8×10⁸ red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.

’623 patent claim 46 (emphases added by the Federal Circuit in its decision).

Prometheus argued that its asserted claims not only satisfy the machine-or-transformation test, but also are not drawn to mere abstractions. Specifically, Prometheus argued that its asserted claims involve a particular transformation of a patient’s body and bodily sample and use particular machines to determine metabolite concentrations in a bodily sample (e.g., via high pressure liquid chromatography), thus satisfying either prong of the machine-or-transformation test. Prometheus further argues that its claims also involve an application of a law of nature, not the law itself, because they recite specific means of treating specific diseases using specific drugs, and therefore do not preempt the abstract idea of calibrating drug dosages to treat disease.

Mayo argued that the Supreme Court in Bilski reaffirmed that preemption is the controlling standard for § 101 under the Court’s Benson, Flook, and Diehr precedents and made clear that while a machine-or-transformation test may inform the analysis, that test is not outcome determinative. And, according to Mayo, under the governing preemption standard, Prometheus’s claims are invalid because they preempt all practical use of naturally occurring correlations between metabolite levels and drug efficacy and any machine or transformation present in the claims is merely insignificant post-solution activity.

Notice how Prometheus and Mayo approach the issue of abstraction. Prometheus couches the argument by focusing on whether the claims are a general abstraction, namely the preempting of calibrating drug dosages to treat disease. Mayo, on the other hand and not at all surprisingly, characterized the abstraction issue as pertaining to the specific subject matter of the claim, focusing on the correlations between the measured metabolite levels and the efficacy of the drug in question. It seems to me that the more appropriate abstraction inquiry is the on offered by Prometheus, which was adopted by the Federal Circuit. For the Federal Circuit to have adopted the Mayo characterization of abstraction it would have needed to ignore the fundamental nature of a patent, which is to exclude. The fact that what is specifically and narrowly claimed preempts ought not to come as a shock to anyone. After all, that is what a patent claim is intended to do, and specifically what the Patent Laws and Congress intended.

In any event, in reaching its decision the Federal Circuit went through the tried and true recitation of the law relative to patent eligible subject matter, explaining that the Supreme Court, even in Bilski v. Kappos, opted for a broad view of what is considered patentable subject matter.  Furthermore, while not explicitly in the text of § 101, the Federal Circuit explained that 150 years of case law teaches that what is not patentable subject matter are laws of nature, physical phenomena, and abstract ideas, although “an application of a law of nature or mathematical formula to a known structure or process may well be deserving of patent protection.” (citing Bilski v. Kappos).

The Federal Circuit went on to pose, and answer, the Prometheus issue in this way:

In light of the Supreme Court’s decision in Bilski, patent eligibility in this case turns on whether Prometheus’s asserted claims are drawn to a natural phenomenon, the patenting of which would entirely preempt its use as in Benson or Flook, or whether the claims are drawn only to a particular application of that phenomenon as in Diehr.  We conclude they are drawn to the latter.

(citations omitted).

The Federal Circuit went on to explain:

[T]he claims recite specific treatment steps, not just the correlations themselves. And the steps involve a particular application of the natural correlations: the treatment of a specific disease by administering specific drugs and measuring specific metabolites. As such, and contrary to Mayo’s assertions, the claims do not preempt all uses of the natural correlations; they utilize them in a series of specific steps… The inventive nature of the claimed methods stems not from preemption of all use of these natural processes, but from the application of a natural phenomenon in a series of steps comprising particular methods of treatment. Other drugs might be administered to optimize the therapeutic efficacy of the claimed treatment.

We similarly reaffirm that the treatment methods claimed in Prometheus’s patents in suit satisfy the transformation prong of the machine-or-transformation test, as they “transform an article into a different state or thing,” and this transformation is “central to the purpose of the claimed process.”

(citations omitted).

But what would become of the claims that do not include the administering step, and instead are limited to the determining step? They would survive as well, with the Federal Circuit explaining:

Not all of the asserted claims, however, contain the administering step. That omission, which occurs in claims 46 and 53 of the ’623 patent, does not diminish the patentability of the claimed methods because we also hold that the determining step, which is present in each of the asserted claims, is transformative and central to the claimed methods. Determining the levels of 6-TG or 6-MMP in a subject necessarily involves a transformation. Some form of manipulation, such as the high pressure liquid chromatography method specified in several of the asserted dependent claims or some other modification of the substances to be measured, is necessary to extract the metabolites from a bodily sample and determine their concentration.

One critical determination, which allowed the Federal Circuit to rule in favor of Prometheus, was the decision that the steps involved in the claims were “not merely insignificant extra-solution activity,” see Flook. The panel concluded, without much discussion, that because the administering and determining steps were transformative they were not merely extra-solution activity. The Federal Circuit then went on to say that the Prometheus claims and case were easily distinguishable from previous cases, which is where the decision seems to get a little dicey. I’m not so sure I would characterize this case as “easily distinguishable.”

The Federal Circuit explained that the closest case was In re Grams, and distinguished it by saying:

In Grams, the applicant claimed a process that involved (1) performing a clinical test on individuals and (2) based on the data from that test, determining if an abnormality existed and determining possible causes of any abnormality by using an algorithm. We found that this process was not drawn to patentable subject matter because the essence of the claimed process was the mathematical algorithm, rather than any transformation of the tested individuals. More specifically, the Grams process was unpatentable because “it was merely an algorithm combined with a data-gathering step,” i.e., performing a clinical test. The claims did not require the performing of clinical tests on individuals that were transformative—and thus rendering the entire process patentable subject matter—because the tests were just to “obtain data.” The patent and thus the court focused only on the algorithm rather than the clinical tests purported to be covered by the claims.

The Federal Circuit went on to explain that the Prometheus administering and determining steps were not merely data-gathering steps, but were part of the treatment regimen.

Finally, the Federal Circuit did determine that the “wherein” clauses of the claims are merely mental processes and not patentable in and of themselves, but because the claims included other steps the overall claims were, in fact, patent eligible subject matter.

So what does this all mean? It is definitely good news for Prometheus, that is for sure. It also seems to be excellent news for medical diagnostic patents as well, provided there are steps included that are other than merely data-gathering steps and mental processes. As long as there are steps recited that are a part of a treatment regimen it seems likely that they will be determined to be transformative and, as a result, not merely insignificant extra-solution activity.

The question remains, however, will it be possible for patent claims to satisfy the machine-or-transformation test and still represent unpatentable subject matter? I continue to think the answer is no, that if claims satisfy machine-or-transformation then there will be patent eligible subject matter. That seems to be how this panel handled the issue, nearly determining that when there is transformation there is not merely insignificant extra-solution activity. I do believe that is the right way to conceptualize the patent eligible subject matter test post-Bilski, but will other panels follow this lead? Time will tell.