CAFC: Method for Calibrating Drug Dosage Is Transformative

Legend has it that Zeus punished Prometheus by binding him to a rock while having his regenerating liver eaten daily by a great eagle. After the case of Prometheus Laboratories, Inc. v. Mayo Collaborative Services, we in the patent world may now be subjected to similar torture in determining when medical/drug dosage calibration methods qualify as statutory subject matter under 35 U.S.C §101. The district court in Prometheus ruled that a patented drug dosage calibration method was non-statutory under 35 U.S.C §101 as essentially correlations of “natural phenomena,” citing Justice Breyer’s dissenting opinion in Laboratory Corp. v. Metabolite Laboratories, Inc. But in the resulting collision with the “machine or transformation” test of In re Bilski, the Federal Circuit held, instead, that this patented method was “transformative,” and therefore statutory subject matter under 35 U.S.C §101.

The patented method in Prometheus determined (calibrated) the proper dosage of thiopurine drugs to treat both gastrointestinal and non-gastrointestinal autoimmune diseases. What the patented method sought to do was optimize therapeutic efficacy while minimizing toxic side effects. The patented method had essentially only two steps: (1) administering the drug to a patient; and (2) determining the level of metabolites of the drug in the patient after administration. The patented method also concluded with some “wherein clauses” that, if certain drug metabolites were below a certain level, that would indicate a need to increase the amount of the drug administered. Conversely, if those drug metabolites were above a certain level, that would indicate a need to decrease the amount of the drug administered.

The district court granted the alleged infringer’s (Mayo’s) motion for summary judgment of invalidity of this patented drug dosage calibration method under 35 U.S.C §101. The district court found the “administering” and “determining” steps to be merely “necessary data-gathering” for use in “correlating” the drug metabolite levels with therapeutic efficacy/toxicity. The district court then found that the final “warning step” (aka the “wherein” clauses) was only a “mental step” requiring no “actual change in dosage.” Accordingly, the district court concluded that the patented drug dosage calibration method only recited “correlations between particular correlations of [drug metabolites] and therapeutic efficacy or toxicity in patients taking the [drugs].” These “correlations were natural phenomena and not patentable inventions because the correlations resulted from a natural body process.”

In reversing the district court’s ruling in Prometheus, Judge Lourie, writing for the Federal Circuit panel, was faced with the unenviable task of trying to reconcile the “natural phenomena” prohibition with the Bilski “machine or transformation” test. First, Judge Lourie concluded that the “administering” and “determining” steps of the patented drug dosage calibration method were “transformative.” Specifically, the “transformation is 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.” In disagreeing with the district court’s “natural phenomena” characterization, Judge Lourie said “we do not view the [patented drug dosage calibration method] as merely claiming natural correlations and data-gathering steps.” In footnote 3, Judge Lourie also took a swipe at Justice Breyer’s dissenting opinion in the Metabolite case (which as noted above was relied upon heavily by the district court), saying “that dissent is not controlling law and also involved different claims from the ones at issue.”

Second, Judge Lourie asserted that the “administering” and “determining” steps were not “merely insignificant extra-solution activity.” Instead, the “administering” step “provides the drugs for the purpose of treating disease,” while the “determining” step “measures the drugs’ metabolite levels for the purpose of assessing the drugs’ dosage during the course of treatment.” As a result, Judge Lourie found the patented drug dosage calibration method in Prometheus to be “easily distinguishable from prior cases that found asserted method claims to be unpatentable for claiming data-gathering steps and a fundamental principle.”

Third, while agreeing with the district court that the “wherein” clauses “are mental steps and thus not patent-eligible per se,” Judge Lourie then said the claimed drug dosage calibration method “is not simply to the mental steps.” As stated by Judge Lourie, a “subsequent mental step does not, by itself, negate the transformative nature of prior steps.” Instead, “when viewed in the proper context, the final step of providing a warning based on the results of the prior steps does not detract from the patentability of” the claimed drug dosage calibration method.

At the conclusion of his opinion, Judge Lourie said “the district court erred in finding that the claims wholly preempt use of correlations between metabolite levels and efficacy or toxicity.” Instead, the patented method is directed “to transformative methods of treatment, not correlations.” Accordingly, the patented method does “not preempt natural processes” because it “utilize[s] them in a series of specific steps.”

With all due respect, Judge Lourie’s opinion in Prometheus is clear evidence of how tortuous it is to apply the Bilski “machine or transformation” test objectively to drug dosage calibration methods like those in Prometheus. In fact, the earlier non-precedential 2008 per curiam decision in Classen Immunotherapies, Inc. v. Biogen Idec presaged how arbitrary the Bilski test can be when applied to such drug/medical dosage calibration techniques. Classen, which came out not long after Bilski, is astounding for its brevity (one paragraph of 69 words), or as Kevin Noonan poignantly observed, the claimed method for essentially calibrating an immunization schedule for a treatment group, relative to a control group, was longer than the opinion by 20 words. But more significantly and as I commented when it came out, Classen is ghastly for completely failing to explain how this “new” Bilski test was applied to the claimed immunization schedule calibration method. And while Prometheus does far more than Classen to explain how Bilski should be applied to such drug/medical dosage calibration methods, I still see much “straining” in Judge Lourie’s opinion in trying to reconcile the “natural phenomena” prohibition with the “machine or transformation” test.

With the Bilski case now before the Supreme Court, there is the unsettling feeling that Prometheus may not be the last word from the courts, including the Federal Circuit, on when drug/medical dosage calibration methods pass muster under 35 U.S.C §101. The Supreme Court’s failure in the Metabolite case to resolve or at least clarify this issue may yet come back to haunt the patenting of these drug/medical dosage calibration methods. And unlike the Prometheus of mythology, we may find being bound to a rock while our liver is repeatedly eaten less tortuous than trying to figure out how to apply the “machine or transformation” test (or whatever Supreme Court decides in Bilski is the correct test for 35 U.S.C §101) to these drug/medical dosage calibration methods.

*© 2009 Eric W. Guttag