It is now just over a year since the U.S. Supreme Court delivered its opinion in Mayo Collaborative Services v. Prometheus Laboratories, Inc., 132 S. Ct. 1289 (2012), and nearly a year since the U.S. Patent and Trademark Office (USPTO) issued its guidelines based on that decision: the 2012 Interim Procedure for Subject Matter Eligibility Analysis of Process Claims Involving Laws of Nature, of July 3, 2012. Despite the passage of time, there have been very few subsequent court decisions considering the patent eligibility of diagnostic method claims. There has been one Federal Circuit decision on diagnostic methods, which found the claims ineligible for patenting, and only a small handful of unpublished decisions from the lower courts that addressed the issue.¹ In addition, a recent Federal Circuit case concerning business methods shows that U.S. judges currently disagree about how to draw the line between patent-eligible and nonpatent-eligible method claims, signaling more uncertainty ahead.²,³

So, how should a patent applicant who wishes to protect a biomarker or personalized medicine invention proceed? First, it is helpful to recognize the type of claim that might come under increased scrutiny in view of Mayo, in order to be prepared to handle a rejection from the USPTO. The claim addressed by the Supreme Court in Mayo was a method claim and recited as follows:
A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising:

  1. administering a drug providing 6–thioguanine to a subject having said immune-mediated gastrointestinal disorder; and
  2. 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 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 indicates a need to decrease the amount of said drug subsequently administered to said subject.

See id. at 1295 (emphases and citation omitted). The Court analyzed whether this claim was patent eligible in two steps. The Court considered (1) whether the claimed method recited some natural law or natural phenomenon, and if so, (2) whether the surrounding active method steps were sufficient to transform that unpatentable natural law into a patentable application of the natural law.

Specifically, the Court concluded that the relationship between the concentration of the 6-thioguanine metabolite and the likelihood that the drug will be effective is a “law of nature.” See id. at 1293, 1296. The Court then turned to the method steps to see whether or not they recited a patentable application of this natural law—that the 6-thioguanine level predicts a response to a thiopurine drug—and concluded that the steps of the method were not sufficient to limit the claim to a patentable application. See id. at 1294, 1297. In the Court’s view, the “administering” and “determining” steps recited in the claims “consist of well-understood, routine, conventional activity already engaged in by the scientific community,” while the “wherein” clauses “simply tell a doctor about the relevant natural laws.” Id. at 1297-98. An overriding concern of the Supreme Court seemed to be a fear of allowing a patent to hinder basic scientific research. In the Court’s view, “[a]nyone 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.” Id. at 1298.

The USPTO guidelines for examining method claims based on Mayo follow this same two-step analysis. One of the USPTO’s example claims is as follows:

A method of determining the increased likelihood of having or developing rheumatoid arthritis in a patient, comprising the steps of:

obtaining a serum sample from a patient;

contacting the serum sample with an anti-IgM antibody; and

determining that the patient has rheumatoid arthritis or an increased likelihood of developing rheumatoid arthritis based upon the increased binding of the anti-IgM antibody to IgM rheumatoid factor in the serum sample.

USPTO Guidelines at 11. According to the USPTO, the relationship between IgM rheumatoid factor levels and rheumatoid arthritis is a natural law, while the steps in the above claim merely recite the natural law with no more than a general instruction to use it, and for that reason, are not sufficient to make the claim patent eligible. Id. at 11-12.

These examples suggest that any process or method claim in which measuring a parameter, e.g., the expression level of a biomarker, is used to predict whether or not a natural event will occur, e.g., a response to a drug or an increased risk for a disease, may be scrutinized for patent eligibility in the USPTO. The examiner may find the fact that the parameter predicts the event to be a “natural law,” and may then look to the individual steps of the method to determine if they are, in the words of the Supreme Court, “well-understood, routine, conventional activity already engaged in by the scientific community.” Mayo, 132 S. Ct. at 1298. If so, the examiner will likely consider the claim not eligible for patenting. Moreover, the USPTO has indicated that even if the relationship between parameter and the event it predicts is newly discovered or is very narrowly claimed, the claims may still be found ineligible for patenting, as these are not factors in the USPTO’s analysis. USPTO Guidelines at 3.

Accordingly, patent applicants who wish to claim diagnostic methods may need to convince the USPTO that the steps of their methods are not “well-understood, routine, [and] conventional.” At present, with very little case law to draw upon, this may be a difficult task. In the absence of such case law, the USTPO seems to have taken a conservative approach, considering method steps to be nonconventional when the steps are themselves novel and nonobvious in view of the prior art or when they incorporate reagents that are novel and nonobvious. For example, the USPTO considers the above example claim, which recites measuring the biomarker level with an antibody, to be unpatentable, but considers narrower claims, in which either the antibody used or the specific method steps are novel and nonobvious, to be patentable. Id. at 11-12. From an applicant’s point of view, those narrower claims may be very easy for a competitor to design around and thus of little commercial value.

So, how should an applicant proceed? First, applicants who wish to continue to use method claims to protect biomarker applications should be prepared to argue that their methods are somehow not conventional in the art and thus will not impinge on basic researchers who want to study the relationship of the biomarker and the event it predicts. With this in mind, practitioners preparing new applications should consider incorporating appropriate fall-back disclosures or dependent claims that recite unique or nonconventional method steps or reagents.

Practitioners handling pending applications as well as preparing new applications should also consider other types of claims. For example, an applicant who is the first to measure a particular biomarker might be able to draft a claim to a method of generating a complex between that biomarker and a detection reagent. Such a claim, in effect, recites a method of generating a non-natural composition and, accordingly, should be patent eligible. Alternatively, given that Mayo concerns only method claims, an applicant may consider composition claims, such as claims reciting a kit of reagents and instructions for carrying out a diagnostic method. In addition, a Federal Circuit case decided prior to Mayo held that a claim reciting a method of treating a patient that incorporates information from a diagnostic assay method is patent eligible. Classen Immunotherapies, Inc. v. Biogen Idec, 659 F.3d 1057, 1067-98 (Fed. Cir. 2011). For example, such a claim might look like the USPTO example claim above incorporating a subsequent step of treating the patient for rheumatoid arthritis with an appropriate drug if the diagnostic assay reveals that the patient suffers from the disease. However, it might be difficult to ultimately prove infringement of such a claim given that a single actor may not perform both the patient treatment and the diagnostic assay steps. Thus, patent applicants should consider whether they can draft a pure method-of-treatment claim that incorporates information from the diagnostic assay, but where all of the steps are likely to be performed by a doctor. Such a claim might have a better chance of withstanding a noninfringement argument.

Note that these alternative strategies such as nonconventional diagnostic assay methods, kits, and method-of-treatment claims generally may result in narrower claims than the traditional diagnostic method claims found patent ineligible by the Supreme Court. Applicants who desire protection for current diagnostic products may wish to consider pursuing these alternatives in spite of their disadvantages, however. In addition, practitioners preparing new applications should consider all of the above claiming strategies when drafting a new application in order to ensure that there will be sufficient support in the application disclosure for such claims. Finally, it may also be helpful to keep applications pending at the USPTO until further case law on diagnostic method claims develops and provides more clarity. In particular, applicants whose products are not expected to go onto the U.S. market soon may wish to delay prosecution of their applications in order to wait for further clarifying case law to emerge.