Tag Archives: Personalized Medicine

The Federal Circuit decided for the second time that the personalized medicine claims at issue in Prometheus Laboratories, Inc. v. Mayo Collaborative Services satisfy the requirements for patent-eligibility set forth in 35 U.S.C. § 101, even under the Supreme Court’s decision in Bilski v. Kappos. In so doing, the court followed a two-part analysis that provides a framework for analyzing other method claims that may raise similar issues.

Prometheus’s Claims

Prometheus’s claims relate to personalized methods of optimizing the dosing of specific drugs used to treat gastrointestinal autoimmune diseases. Representative claims from the Prometheus’s patents are set forth below.

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.

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.

Thus, while many claims recite both an “administering” step and a “determining” step, some claims recite only a “determining” step.

The Road to the Supreme Court – The District Court & The Metabolite Dissent

The district court had invalidated Prometheus’s claims under 35 U.S.C. § 101, applying the rationale from Supreme Court Justice Breyer’s 2006 dissent to the dismissal of certiorari in Laboratory Corp. of American Holdings v. Metabolite Labs., Inc.

The claims at issue in Metabolite recited:

A method for detecting a deficiency of cobalamin or folate in warm-blooded animals comprising the steps of:
assaying a body fluid for an elevated level of total homocysteine; and
correlating an elevated level of total homocysteine in said body fluid with a deficiency of cobalamin or folate.

Justice Breyer summed up the claimed methods as involving only

1. obtaining test results and
2. thinking about them.

He opined that the claims “embody only the correlation between homocysteine and vitamin deficiency that the researchers uncovered. In my view, that correlation is an unpatentable ‘natural phenomenon.’”

The Road to the Supreme Court – The Federal Circuit’s 2009 Decision

Prometheus appealed to the Federal Circuit, who reversed the district court in a decision issued in 2009. The Federal Circuit found that the claims satisfied § 101 under its machine-or-transformation test, because the methods “transform a particular article into a different state or thing.”

The “administering” claims do so because they “are in effect claims to methods of treatment, which are always transformative.”

The “determining” claims do so, because the level of 6-thioguanine or 6-methylmercaptopurine “cannot be determined by mere inspection,” but requires transformative chemical analysis, such as high-performance liquid chromatography (HPLC).

The Federal Circuit rejected arguments that the administering and determining steps were “insignificant post-solution activities” or merely “data gathering,” but found instead that they were “central to the claims,” “part of a treatment protocol” and “transformative.” The Federal Circuit also stated that the “mental steps” embodied in the “wherein” clauses were not fatal to patentability when the claims were considered as a whole.

The Supreme Court GVR Order

Mayo petitioned the Supreme Court for certiorari, which the Court granted, but only to vacate the Federal Circuit decision and remand to the Federal Circuit in view of its decision in Bilski v. Kappos.  (This is referred to as a “GVR order” for “grant,” “vacate,” and “remand.)

Back at the Federal Circuit

On remand, the Federal Circuit requested new briefs from the parties, and accepted seven amicus briefs. Prometheus argued that its claims should be found to be patent-eligible because the Supreme Court did not invalidate the machine-or-transformation test, while Mayo argued that the claims do not satisfy § 101 because they preempt all practical uses of a natural phenomenon.

The Federal Circuit began its analysis by noting that the Supreme Court has consistently construed § 101 broadly, in accord with Congressional intent, as reflected in the “expansive terms” used in the statute. The Federal Circuit nevertheless acknowledged that § 101 is not unlimited, because Supreme Court precedent provides three specific exceptions to § 101’s broad patent-eligibility principles:

laws of nature, physical phenomena, and abstract ideas.

On this point, the Federal Circuit noted that Supreme Court precedent also holds that “an application of a law of nature or mathematical formula to a known structure or process may well be deserving of patent protection.”

Turning to case before it, the Federal Circuit characterized the issue on remand 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’s Two-Part Analysis

The Federal Circuit rejected Mayo’s argument (which has been echoed in speculation from the patent bar) that the Supreme Court’s Bilksi decision or its remand of this case required a “wholly different analysis or a different result.” To the contrary, the Federal Circuit stated that the Supreme Court’s Bilksi decision “did not undermine our preemption analysis” and “did not disavow the machine-or-transformation test.”

The Federal Circuit reconsidered Prometheus’s claims under a two-part analysis:

1.   The court explained that the claimed methods “recite a patent-eligible application of naturally occurring correlations between metabolite levels and efficacy or toxicity, and thus do not wholly preempt all uses of the recited correlations.”

In reaching this conclusion, the court noted:

[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.

2.   The court confirmed that the claimed methods satisfy the machine-or-transformation test.

Again, the court expressed its belief that “administering a drug” always involves a transformation, because “[t]he drugs do not pass through the body untouched without affecting it” or without being metabolized.

The court emphasized that the fact that the method “relies on natural processes does not disqualify the administering step from the realm of patentability.” The court agreed with Prometheus that “every transformation of physical matter can be described as occurring according to natural processes and natural law.” But, the court said, ”[t]he transformation here . . . is the result of the physical administration of a drug to a subject to transform—i.e., treat—the subject, which is itself not a natural process.” 

With regard to the “determining” claims that do not include an “administering” step, the court noted that “[s]ome form of manipulation, such as the high pressure liquid chromatography method specified in several of the asserted dependent claims . . . is necessary to extract the metabolites from a bodily sample and determine their concentration.” Thus, these claims satisfy the test as inherently involving a transformation. 

This two-part analysis is similar to the USPTO’s Interim Bilski Guidance (promulgated July 27, 2010), which advises examiners to evaluate patent-eligibility of method claims by (1) considering whether the claimed method is directed to an abstract idea and (2) determining if it satisfies the machine-or-transformation test.

Other Exclusions Ruled Out

The Federal Circuit (again) rejected arguments that the “administering” and “determining” steps were mere “data gathering” steps or “insignificant extra-solution activity.” To the contrary, the court found that the steps were “central to the purpose of the claims, which the court found to be “optimizing efficacy and reducing toxicity of treatment regimes.” 

The Federal Circuit also (again) made clear that the presence of the “mental steps” in the “wherein” clauses did not defeat patent-eligibility, because the claims must be evaluated as a whole:

A subsequent mental step does not, by itself, negate the transformative nature of prior steps.

Because “[n]o claim in the Prometheus patents claims only mental steps” the prohibition against patenting mental steps per se did not impact Prometheus’s claims. 

The Bottom Line

The Federal Circuit wrapped up its opinion with this query:

[W]hen asked the critical question, “What did the applicant invent?,” . . . the answer is a series of transformative steps that optimizes efficacy and reduces toxicity of a method of treatment for particular diseases using particular drugs.

By emphasizing these characteristics in this case, the court may be leaving itself room to reach different results in different cases, including Classen Immunotherapies, Inc. v. Biogen Idec (PDF) and Association for Molecular Pathology v. USPTO (the ACLU/Myriad BRCA1 case).

While much of this Prometheus decision reiterates the analysis from the 2009 Federal Circuit decision, the fact that there is “nothing new here” is news. The Supreme Court’s GVR order had cast a shadow of uncertainty over the patent-eligibility of personalized medicine methods, even as health care innovators and practitioners are promoting personalized medicine as offering the promise of more effective—and more cost-effective—treatments. Now the Federal Circuit has provided some guidance on the types of claims that can be found to satisfy § 101 post-Bilski, and has hinted at the types of claims that may be found to go too far.