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Claims to Methods of Optimizing Therapeutic Efficacy Are Patent-Eligible Subject Matter Under 35 U.S.C. § 101

September 16, 2009

Decision icon Decision

Last Month at the Federal Circuit - October 2009

Judges: Michel, Lourie (author), Clark (District Judge sitting by designation)

[Appealed from: S.D. Cal., Judge Houston]

In Prometheus Laboratories, Inc. v. Mayo Collaborative Services, No. 08-1403 (Fed. Cir. Sept. 16, 2009), the Federal Circuit reversed the district court’s grant of SJ of invalidity and held that the asserted claims of U.S. Patent Nos. 6,355,623 (“the ’623 patent”) and 6,680,302 (“the ’302 patent”) were drawn to statutory subject matter and therefore not invalid under 35 U.S.C. § 101.

The patents claim methods for calibrating the dosage of thiopurine drugs used for treating certain autoimmune diseases. 6-mercaptopurine (“6-MP”) and the prodrug azathiopurine, which first converts to 6-MP in the body, are converted to various metabolites, including 6-methyl-mercaptopurine (“6-MMP”) and 6-thioguanine (“6-TG”). The claimed methods involve measuring these metabolites to optimize therapeutic efficacy while minimizing toxicity.

The methods typically include two steps: (1) “administering” a drug that provides 6-TG to a subject, and (2) “determining” the levels of the drug’s metabolites, 6-TG and/or 6-MMP, in the subject. The claims further recite that the metabolite levels are compared to predetermined metabolite levels, “wherein” the measured levels “indicate a need” to vary the amount of drug to be administered to maximize efficacy and minimize toxicity.

Prometheus Laboratories, Inc. (“Prometheus”) marketed a test that used the claimed methods. Mayo Collaborative Services and Mayo Clinic Rochester (collectively “Mayo”) purchased and used Prometheus’s test, but in 2004, Mayo announced that it would make a test measuring the same metabolites for its own use and sale. Prometheus brought a suit for patent infringement, asserting certain claims of the ’623 and ’302 patents. After Prometheus filed the lawsuit, Mayo rescinded its announcement and has still not launched its test. The parties filed cross-motions for SJ regarding infringement of claim 7 of the ’623 patent. The district court construed “indicates a need” to mean “a warning that an adjustment in dosage may be required.” Slip op. at 4. Mayo then moved for SJ of invalidity under 35 U.S.C. § 101. Mayo argued that the claims recite unpatentable subject matter because the correlations between metabolite levels and efficacy and toxicity are natural phenomena, and the claims wholly preempt use of the natural phenomena. The district court granted SJ of invalidity, finding that the administering and determining steps were merely data-gathering steps for the correlation, and that the final step, construed to be a “warning,” was only a mental step. The district court also concluded that the inventors did not “invent” the claimed correlation but merely observed the relationship between the metabolites and therapeutic efficacy and toxicity. Thus, according to the district court, the claims covered the correlation itself and impermissibly wholly preempted the correlation.

On appeal, the Federal Circuit noted that while the Supreme Court has construed § 101 broadly, § 101 is not unlimited and does not embrace every discovery. The Supreme Court has held that a claim to a process is not patent-eligible if it claims laws of nature, natural phenomena, and abstract ideas. Although claims to a fundamental principle are unpatentable, an application of a law of nature may be deserving of patent protection. Thus, the Federal Circuit stated that the key issue for patentability on the present facts was whether a claim is drawn to a fundamental principle or an application of a fundamental principle.

The Federal Circuit then referred to its “definitive test” regarding statutory subject matter set forth in In re Bilski, 545 F.3d 943 (Fed. Cir. 2008) (en banc), cert. granted, 129 S. Ct. 2735 (June 1, 2009). The machine-or-transformation test states, “A claimed process is surely patent-eligible under § 101 if: (1) it is tied to a particular machine or apparatus, or (2) it transforms a particular article into a different state or thing.” Slip op. at 8. The Court further highlighted that the use of a machine or transformation of an article must impose meaningful limits on the claim and must not be insignificant extra-solution activity or merely a data-gathering step. If steps of a method represent data gathering rather than being “central” to the purpose of the process, then the patentee likely cannot rely on the data-gathering steps to prove that the claimed process is transformative and thus drawn to patentable subject matter.

The Federal Circuit concluded that the claimed methods of treatment are patentable subject matter because they transform an article into a different state or thing, and the transformation is central to the purpose of the claimed process. The Court held that the transformation was of the human body following administration of a drug and the various chemical and physical changes of the drug’s metabolites that enable their concentrations to be determined. Because the claimed methods met the transformation prong under Bilski, the Court did not consider whether they also met the machine prong.

The Court did not consider the disputed claims as merely claiming natural correlations and data-gathering steps. The Court noted that methods of treatment are always transformative when a defined group of drugs is administered to the body to ameliorate the effects of an undesired condition. When administering thiopurine drugs, the body necessarily undergoes a transformation, and the effect on the body after metabolizing the artificially administered drugs is the entire purpose of administering the drugs. Here, the transformation was 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. Thus, the Court held that the administering step was a significant transformative element of the claimed method.

Even though some claims did not recite a transforming step, the Federal Circuit held that all the claims were nonetheless patentable because the determining step, which was present in each of the asserted claims, was also transformative and central to the invention. Determining the level of metabolites in a patient necessarily involves a transformation. Some form of manipulation was necessary to extract the metabolites from a sample and determine their concentration. The Court rejected Mayo’s argument that this was simply a data-gathering step for use of the correlations. The Court found that the transformation was central to the purpose of the claims since the determining step was a significant part of the claimed method of treatment. Thus, by working a chemical and physical transformation on physical substances, the Court held that the determining step sufficiently confined the patent monopoly within definite bounds.

The Federal Circuit then stated that the administering and determining steps are not insignificant extra-solution activity or mere data gathering. The Court noted that although these steps gather useful data, these steps were not “‘merely’ for the purpose of gathering data.” Id. at 18. The steps were part of a treatment protocol, and they were transformative.

Next, the Federal Circuit agreed with the district court that the final “wherein” clauses were mental steps and not patent-eligible per se. But the Court noted that a subsequent mental step does not, by itself, negate the transformative nature of prior steps. The data obtained in the administering and determining steps for use in the mental step were obtained by steps well within the realm of patentable subject matter. As the Court noted in Bilski, even though a fundmental principle itself is not patent-eligible, processes incorporating a fundamental principle may be patent-eligible. Thus, it is irrelevant that any individual step by itself would be unpatentable under § 101. Here, when viewing the treatment methods as a whole, the Court found that Prometheus invented a series of transformative steps that optimizes efficacy and reduces toxicity of a method of treatment for particular diseases using particular drugs.

Finally, the Federal Circuit held that the district court erred in finding that the claims wholly preempt the use of correlations between metabolite levels and efficacy or toxicity. The Court found that the claims cover transformative methods of treatment, which are a particular application of natural processes, and not simply the correlation itself. Regardless, the Court noted that because the claims met the machine-or-transformation test, they did not preempt a fundamental principle. Thus, the Court held that “[t]he inventive nature of the claimed methods stem[med] not from preemption of all use of these natural processes, but from the application of a natural phenomenon in a series of transformative steps comprising particular methods of treatment.” Id. at 22

Summary authored by David Albagli, Ph.D., Esq.