On March 20, 2012, Justice Breyer issued the unanimous decision for the Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories, Inc., holding that Prometheus’ claims directed to methods of optimizing the dose of specific drugs used in the treatment of specific conditions are invalid under 35 USC § 101 because they impermissibly claim laws of nature. The Court’s decision reverses the Federal Circuit, which had twice upheld the validity of the claims at issue. While the Court’s opinion provides additional touchstones for distinguishing claims directed to laws of nature (not patent-eligible) from claims directed to specific applications of laws of nature (patent-eligible), because it erases the bright line of the Federal Circuit’s machine-or-transformation test, stakeholders will have to undertake a fact-specific, case-by-case, and (at least for the time being) uncertain analysis in order to determine whether given personalized medicine method claims satisfy § 101.

The Claims at Issue

The Supreme Court focused on claim 1 as being representative of the claims at issue:

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 . . . and
(b) determining a level of 6-thioguanine in the subject . . .
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.

The Federal Circuit Decisions

In its original 2009 decision, the Federal Circuit applied its machine-or-transformation test for patent-eligibility, and held that the method claims satisfied § 101 by meeting the “transformation” prong of the test. As stated by the Federal Circuit, the “asserted claims are in effect claims to methods of treatment, which are always transformative when a defined group of drugs is administered to the body to ameliorate the effects of an undesired condition.”

Subsequently, the Supreme Court held in Bilski that the “machine or transformation test” is not the “only” way to evaluate compliance with § 101, although it can be a useful clue or tool for analyzing § 101 compliance. After deciding Bilski, the Supreme Court vacated its original grant of certiorari in Prometheus, and remanded the case to the Federal Circuit.

On remand, the Federal Circuit characterized the issue as “whether Prometheus’s asserted claims are drawn to a natural phenomenon, the patenting of which would entirely preempt its use . . ., or . . . only to a particular application of that phenomenon,” which would be patent-eligible. The Federal Circuit again upheld the claims, finding that they relate to administering specific drugs and measuring specific metabolites, and so do not preempt all uses of natural correlations, but rather utilize them in a series of specific steps relating to particular methods of treatment. (For a more detailed review of this case, please see this previous article.)

Justice Breyer Has His Say

To many following Prometheus, the Federal Circuit decisions were somewhat at odds with Justice Breyer’s dissent from the dismissal of the grant of certiorari in Laboratory Corp. of America Holdings v. Metabolite Laboratories, Inc. In both of its decisions (before and after Bilski), the Federal Circuit addressed Metabolite only in a footnote. I wondered if the court was setting itself up for a confrontation with Justice Breyer, and am not surprised that Justice Breyer finally got his say by authoring the Supreme Court decision.

Justice Breyer began his unanimous opinion for the Court by citing the language of 35 USC § 101, and noting that “[t]he Court has long held that this provision contains an important implicit exception:

“[L]aws of nature, natural phenomena, and abstract ideas” are not patentable.

Perhaps taking a dig at the Federal Circuit’s machine-or-transformation test, Justice Breyer phrased the issue before the Court in terms of what is required “to transform an unpatentable law of nature into a patent-eligible application of such a law.” The Court emphasized that the difference should depend not merely on words, but on underlying principles, and read earlier Supreme Court precedent (such as Flook and Bilski) as holding that

a process that focuses upon the use of a natural law also contain other elements or a combination of elements, sometimes referred to as an ‘inventive concept,’ sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the natural law itself.

Turning to Prometheus’ claims, the Court characterized them as “set[ting] forth laws of nature—namely, relationships between concentrations of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm.” The Court thus framed the issue before it as whether “the patent claims add enough to their statements of the correlations to allow the processes they describe to qualify as patent-eligible processes that apply natural laws.” The Court decided that the recited “administering,” “determining” and “wherein” steps are not sufficient to “transform the nature of the claim” into one that is patent-eligible.

The Court considered the “administering” step as “simply refer[ring] to the relevant audience,” which was a “preexisting audience,” because doctors already knew to use thiopurine drugs to treat the recited conditions. The Court suggested that even a new “audience” might not have saved the claims, noting that the “‘prohibition against patenting abstract ideas “cannot be circumvented by attempting to limit the use of the formula to a particular technological environment.”‘”

The Court found the “wherein” clauses to do little more than “simply tell a doctor about the relevant natural laws, at most adding a suggestion that he should take those laws into account when treating his patient.”

The Court gave more consideration to the “determining” step, but found it not to bring the claims under § 101 because “methods for determining metabolite levels were well known in the art.” The Court cited the principle that “[p]urely ‘conventional or obvious’ ‘[pre]-solution activity’ is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law.”

Finally, the Court considered the claims as a whole, but found that looking at “the three steps as an ordered combination adds nothing to the laws of nature that is not already present when the steps are considered separately.”

Anyone who wants to make use of these laws must first administer a thiopurine drug and measure the resulting metabolite concentrations, and so the combination amounts to nothing significantly more than an instruction to doctors to apply the applicable laws when treating their patients.

Summarizing the holding, the Court states:

To put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately. For these reasons we believe that the steps are not sufficient to transform unpatentable natural correlations into patentable applications of those regularities.

Looking Back

Many may view the Court’s decision as upsetting the status quo of patent-eligibility that has been followed by the USPTO and upheld by the Federal Circuit. Patent holders in the personalized medicine space should consider seeking the advice of patent counsel, to determine whether this decision may be relevant to the validity of their patents. Even if the granted claims look uncomfortably similar to Prometheus’ claims, it may be possible to strengthen or uphold the validity of the patent through the reissue process. A similar approach can be taken in pending applications, such as by amending or adding claims to more directly focus on specific applications of any underlying laws of nature.

Looking Ahead

While the Court informs us of the importance of reciting “additional features” to take claims beyond a law of nature, it does not provide much concrete guidance on how to “add enough” so that the claims “qualify as patent-eligible processes that apply natural laws.” Clearly, the Court will not give much weight to any “conventional” steps that are recited in the claims, even if they are concrete or physically transformative. Additionally, the Court seems to say that if a law of nature itself has a limited application, any claims based on such a law of nature must be even more narrow, so as not to preclude others from exploiting or innovating around the law of nature. Although the Court expressed concerns that satisfaction of § 101 should not hinge on clever claim drafting, it is inevitable that patent practitioners like myself will keep this decision in mind as we try to craft claims that look more like those upheld in Diehr and less like those invalidated in Flook and now Prometheus.

While Justice Breyer had the last word here, it is important that patents still be sought and granted in the field of personalized medicine, so that the patent system can continue to incentivize and reward essential research in this area.