In Prometheus Labs. v. Mayo Collaborative Services and Mayo Clinic Rochester (“Prometheus”), the Federal Circuit rejected Mayo’s patentable subject matter challenge under 35 U.S.C. § 101, and overturned the district court, holding that Prometheus’ claimed methods for calibrating a drug dosage meet the machine-or-transformation test recently applied in In re Bilski, 545 F.3d 943 (Fed. Cir. 2008) (“Bilski”).

The court distinguished the claimed methods, which require actual administration of drugs into the body, from diagnosis claims that merely require data gathering and correlation.

In particular, the court ruled that the injection of a drug into a subject, together with the determination of the consequent metabolites of the drug, is part of a treatment protocol that meets the transformation prong of the test applied in Bilski.

In Bilski, the Federal Circuit attempted to clarify the standards applicable in determining whether a claimed method constitutes a statutory “process” under Section 101.

Per the court, the test for a method claim is whether the claimed method is (1) tied to a particular machine or apparatus, or (2) transforms a particular article to a different state or thing, i.e., the “machine-ortransformation test.” In addition, the transformation must be an “integral” part of the claimed method. In Prometheus, the Federal Circuit ruled that the administration or injection of a drug into a subject “transforms an article into a different state or thing” and that this transformation was an integral part of the claimed methods. Indeed, the whole point of administering the drug is to provide its metabolites for treatment of disease.

While the Federal Circuit in Prometheus might have noted in footnote 2 that, “even prior to Bilski, the asserted claims should have been found to be patentable subject matter,” please note that Bilski is now on appeal at the Supreme Court. For that reason, the test for patentable subject matter under Section 101 should be not be considered entirely certain. In other words, it is possible that the test for patentable subject matter employed in Prometheus might not hold up under the Supreme Court’s review. This case summary, however, does not consider whether the scope of patentable subject matter will be narrowed, broadened or possibly stay the same.

In the present case, Prometheus appealed from the district court’s grant of summary judgment of invalidity of U.S. Patent Nos. 6,355,623 (“the ‘623 patent”) and 6,680,302 (“the ‘302 patent”) under 35 U.S.C. § 101.

Prometheus is the sole and exclusive licensee of both the ‘623 patent the ‘302 patent. The patents claim methods for calibrating the proper dosage of thiopurine drugs, which are used for treating both gastrointestinal and non-gastrointestinal autoimmune diseases. The thiopurine drugs of the claimed methods, 6-mercaptopurine (6-MP) and azathipurine (AZA) convert into various 6-MP metabolites upon administration to a patient, such as 6- thioguanine or “6-TG” and 6- methyl-mercaptopurine or “6-MMP.” The claims at issue involve the measurements of these two metabolites.

It was known in the art to use these drugs for treatment of autoimmune diseases. However, treatment with these thiopurine drugs was not always effective because of nonresponsiveness and drug toxicity.

Accordingly, the claimed methods are directed to “reducing toxicity” and/or “optimizing therapeutic efficacy.” The claimed methods typically include the following steps (a) “administering” a drug that provides 6-TG to a subject and (b) “determining” the levels of the metabolites 6-TG and/or 6-MMP in the subject. The metabolite levels can then be compared to predetermined threshold values that “indicate a need” to increase or decrease the level of the drug administered to the subject (without actually requiring that a change in dosage). For example, Claim 1 of the ‘623 patent is representative of the claims asserted in this case: A method of optimizing therapeutic efficacy for treatment of an immunemediated gastrointestinal disorder, comprising: (a) administering a drug providing 6- thioguanine to a subject having said immune-mediated gastrointestinal dis order; and (b) determining the level of 6- thioguanine in said subject having said immune-mediated gastrointestinal dis order, wherein the level of 6-thioguanine less than about 230 pmol per 8x108 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 8x108 red blood cells indi cates a need to de crease the amount of said drug subse quently adminis tered to said sub ject.

Claim 1 of the ‘302 patent is substantially the same, except that the level of 6-MMP is determined in addition to the level of 6-TG.

Prometheus marketed a PROMETHEUS Thiopurine Metabolites test that employed the technology covered by the claimed methods. Mayo formerly purchased and used Prometheus’s test, but subsequently decided in 2004 to begin using (and selling to other hospitals) its own test, which measured the same metabolites as Prometheus’s test. In June of 2004, Prometheus sued Mayo for infringement of the patents.

In the district court, Mayo argued that the claimed methods are directed to unpatentable subject matter under Section 101, asserting that the claimed methods simply recite correlations between thiopurine drug metabolite levels and efficacy and toxicity. According to Mayo, this would impermissibly claim and wholly preempt the use of this natural phenomena.

The district court agreed with Mayo that the patents claimed the correlations between thiopurine drug metabolite levels and therapeutic efficacy and toxicity. The district court was not persuaded by the fact that the inventors framed the claims as treatment methods. Instead, the district court found that the “administering” and “determining” steps are merely necessary datagathering steps for the correlations and that the “warning” step (i.e., the wherein clause) is only a mental step. The district court also agreed with Mayo that the correlations are natural phenomena, since the correlations resulted from a natural body process. The district court further reasoned that the inventors did not actually invent the correlation, but merely observed the relationship between the metabolite levels and therapeutic efficacy and toxicity.

The district court thus reasoned that the claims cover the correlations themselves and, thereby, wholly preempt the correlations. Accordingly, the district court considered Prometheus’ claimed methods to be directed to unpatentable subject matter under Section 101.

The Federal Circuit disagreed with the analysis of the district court.

The Federal Circuit agreed that a claim to a process is not patenteligible if it claims “laws of nature, natural phenomena, and abstract ideas,” which it refers to more generally as a fundamental principle.

However, the Federal Circuit cautioned that “while a claim drawn to a fundamental principle is unpatentable,” the “application of a law of nature or mathematical formula to a known structure or process may well be deserving of patent protection.” Per the court in Prometheus, this distinction is the key issue for patentability under Section 101.

In this regard, the Federal Circuit indicated that its two-pronged machine- or-transformation test, recently articulated in Bilski, is a more definitive test for patentable subject matter eligibility. Further, it noted that it is important that “the use of specific machine or transformation impose meaningful limits on the claim’s scope” and that the “involvement of the machine or transformation in the claimed process must not merely be insignificant extra-solution activity” or merely a “data-gathering step.” In other words, the transformative step(s) must be “central” or “integral” the claimed method.

On appeal, with respect to the transformation prong, Prometheus pointed out that (1) the step of administering a drug transforms the patient’s body for the purpose of treating a disease; (2) the step of determining requires the transformation of a bodily sample to determine metabolite levels; and (3) the metabolite levels are transformed into a warning for the doctor. Making an interesting point, Prometheus asserted that administering drugs to a patient should not be considered unpatentable under Bilski simply because it occur within the body and/or proceeds according to natural law. Instead, Prometheus contends that “everything proceeds according to natural laws.” Of course, Mayo argued that there is no patentable transformation. In particular, Mayo again argued that the claimed administering step is merely a data-gathering step. In contrast to Prometheus’ position, Mayo contends that the body’s reaction to the drugs is natural. Mayo also argued that the determining step is a data-gathering step, which is necessary to make use of the claimed correlations.

The Federal Circuit agreed with Prometheus, and in particular, disagreed with the district court that the methods are merely claiming natural correlations in datagathering steps. The Federal Circuit ruled that the claims are drawn 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.” More specifically, the claimed methods were drawn to optimizing therapeutic efficacy and reducing toxicity.

Furthermore, in the claimed methods, the Federal Circuit found that the body necessarily undergoes a transformation when the drugs are administered. In fact, the court stated that the whole point of administering the drug is to provide its metabolites for treatment of disease.

Accordingly, the court believed that this transformation is not merely data-gathering but, instead, is a significant transformative element. In addition, the Federal Circuit agreed with Prometheus that it was immaterial that the change in the drug to its metabolites relies on natural processes within the body. In other words, the court agreed that transformations can operate by natural principles.

The Federal Circuit also found the determining step to be transformative because determining the levels of the drug metabolites “cannot be determined by mere inspection.” The sample of bodily fluid must be manipulated in some way. Mayo, however, did not dispute that this step was transformative, but instead insisted the determining step was merely data-gathering for the correlations.

The court disagreed, stating that the determining step is central to the purpose of the claims, since it is significant to the claimed treatment.

In addition, the Federal Circuit found that the district court’s error was failing to recognize that the administering and determining steps are not merely data-gathering steps.

The court agreed that these two steps gather useful data, however, the court found that “the presence of these two steps is not ‘merely’ for the purpose of gathering data.” The administering and determining steps are “part of a treatment protocol, and they are transformative.” Like-wise, because the claims are drawn to transformative methods of treatment, and not correlations, the Federal Circuit found that the claims do not wholly preempt the use of a natural process. On the contrary, while the claims might cover a particular application of natural processes to treat various diseases, transformative steps utilizing natural processes are not unpatentable subject matter. Moreover, the claims do not preempt natural processes; they utilize them in a series of specific steps.

The Federal Circuit agreed with district court that the final “wherein” clauses of the claimed methods are simply mental steps, which by themselves, are not patent-eligible.

However, the presence of the mental steps “does not detract from the patentability of the administering and determining steps.” In other words, a process incorporating a fundamental principle may be patentable, i.e., a claim as a whole cannot be rendered unpatentable under Section 101 by looking at the eligibility of selected limitations.

Finally, please note that Prometheus also argued that the claims met the machine prong of the machine-ortransformation test. However, because the Federal Circuit found that the claimed methods meet the transformation prong of Bilski, the question of whether the claims meet the machine prong was not considered.