By Kevin E. Noonan —
Diagnostic method claims, especially medical diagnostic method claims, have come under increased scrutiny ever since Justice Breyer (joined by since-retired Justices Souter and Stevens) dissented from dismissal of certiorari as improvidently granted in the Laboratory Corp. v. Metabolite Labs., Inc. ("LabCorp") case. While these considerations have largely been relegated to the background in view of the Federal Circuit's (and Supreme Court's) focus on the Bilski case, the issues raised by the Metabolite claims, and the impending reconsideration of Prometheus Laboratories, Inc. v. Mayo Collaborative Services and Classen Immunotherapies, Inc. v. Biogen Idec cases by the Federal Circuit on remand from the Supreme Court in view of its Bilski v. Kappos decision, serve as a reminder that the issues raised by the Metabolite dissent have neither gone away nor been adequately resolved.
Diagnostic method claims are different from other statutory subject matter because they relate to an intangible product — information. The other statutory subject matter classes — machines, manufactures, and compositions of matter — are all tangible entities, capable of isolation, manipulation, and transformation. Methods of making and methods of using these other statutory categories also result in tangible embodiments. Diagnostic method claims, on the other hand, are directed to producing information, an intangible product, and it is (in part) this intangibility that provokes the philosophical and analytical difficulties that have arisen with regard to patenting this type of claim.
As Professor Kevin Collins (at left; now at the Washington University School of Law) has noted, diagnostic method claims have a general structure as comprising one or more "determining" steps and an "inferring" step, which can be considered as a "mental" step but is perhaps more profitably regarded as a step using the information obtained from the determining step(s) to arrive at a conclusion. These claims are also typically characterized by a preamble that sets forth the activity (predicting, diagnosing, etc.) performed based on the inference.
Importantly, information is not, per se, patentable subject matter, at least because it is not recited as one of the statutory categories under 35 U.S.C. § 101. Indeed, in the software field methods for manipulating information have had a variable reception as patent-eligible subject mater (Benson v. Gottschalk, Parker v. Flook, Diamond v. Diehr, Bilski v. Kappos), with the Supreme Court predominantly limiting patent-eligibility to instances where information was used to produce a real-world effect (and not to pre-empt all uses of the information. In the biotechnology field, the only case partially on point is Bayer AG v. Housey Pharm Inc., where the Federal Circuit held that information produced by the practice of the claimed method was not a product that was imported (and thus infringing) under 35 U.S.C. § 271(g); the claim at issue recited the following method:
A method of determining whether a substance is an inhibitor or activator of a protein whose production by a cell evokes a responsive change in a phenotypic characteristic other than the level of said protein in said cell per se, which comprises:
(a) providing a first cell line which produces said protein and exhibits said phenotypic response to the protein;
(b) providing a second cell line which produces the protein at a lower level than the first cell line, or does not produce the protein at all, and which exhibits said phenotypic response to the protein to a lesser degree or not at all;
(c) incubating the substance with the first and second cell lines; and
(d) comparing the phenotypic response of the first cell line to the substance with the phenotypic response of the second cell line to the substance.
The questions naturally arise, why (and whether) medical diagnostic claims are different from other types of diagnostic claims. Consider the following hypothetical claims:
• Hypothetical claim 1
A method for predicting a nuclear power plant reactor failure, comprising the steps of assaying pressure in a reactor coolant tank and correlating pressure fluctuations with the likelihood of failure, wherein a pressure fluctuation of +/- 7% indicates a greater than 90% likelihood that the reactor will fail.
• Hypothetical claim 2
A method for predicting escalation of a hurricane to Category 5 status, comprising the steps of assaying ocean temperature along a predicted storm track, wherein the hurricane is predicted to achieve Category 5 status if the ocean temperature changes by more than 5 degrees Celsius over less than 100 miles of the storm track.
In comparison with medical diagnostic method claims:
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.
Laboratory Corp. v. Metabolite Labs., Inc.:
A method of determining whether an immunization schedule affects the incidence or severity of a chronic immune-mediated disorder in a treatment group of mammals, relative to a control group of mammals, which comprises immunizing mammals in the treatment group of mammals with one or more doses of one or more immunogens, according to said immunization schedule, and comparing the incidence, prevalence, frequency or severity of said chronic immune-mediated disorder or the level of a marker of such a disorder, in the treatment group, with that in the control group.
Classen Immunotherapeutics, Inc. v. Biogen Idec:
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 X 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 X 108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.
Prometheus Labs., Inc. v. Mayo Collaborative Services:
A method for diagnosing a predisposition for breast cancer in a human subject which comprises comparing the germline sequence of the BRCA2 gene or the sequence of its mRNA in a tissue sample from said subject with the germline sequence of the wild-type BRCA2 gene or the sequence of its mRNA, wherein an alteration in the germline sequence of the BRCA2 gene or the sequence of its mRNA of the subject indicates a predisposition to said cancer.
Claim 2 of U.S. Patent No. 6,033,857, invalidated in AMP v. USPTO ("Myriad").
Comparing these claims, the question naturally arises whether there are differences in structure (using Professor Collins metric, there are not) or differences in application. One difference between the claims in the Classen, Prometheus, and Myriad cases and the other claims is that these "real" claims are all medical diagnostic claims directed to obtaining medical information about a patient. This implicates the doctor-patient relationship, an implication certainly relevant to Justice Breyer in his dissent in Metabolite:
As construed by the Federal Circuit, claim 13 provides those researchers with control over doctors' efforts to use that correlation to diagnose vitamin deficiencies in a patient.
There is precedent for making this distinction, specifically 35 U.S.C. § 287(c), which exempted medical doctors from patent infringement liability for practicing patented surgical methods. There are other considerations for patenting medical diagnostic claims that need to be part of this debate. The first is the potential for a "patent thicket," as genetic information relevant to diagnoses is elucidated. The existence of multiple rights-holders to method claims relating to correlations between genotype and disease state or propensity raises the possibility (but not the certainty) that this multiplicity could inhibit advances in personalized medicine and other applications of this genetic information. On the other hand, precluding patenting raises the possibility that other means of protecting intellectual property — such as trade secret protection — will be more attractive, particularly to larger companies who would benefit from being able to avoid disclosing proprietary relationships between genetic polymorphism and disease (or the likelihood of developing a disease). However, changing the incentives in this way would also destroy the incentives for relations between academic scientists (who need to publish their results) and industry (who would be forced to conceal such diagnostic correlations), to the detriment of the rest of us who have benefitted from the academic-industry collaboration in biotechnology for the past 30 years.
For now, the path forward depends in large part on how the Federal Circuit decides the Classen, Prometheus, and Myriad cases. The present situation is ironic, at least because Congress intended to reduce uncertainty in U.S. patent law by creating the Federal Circuit almost 30 years ago. In some ways, the law is even more uncertain today that it was then, under the sporadic and indifferent tutelage of the Supreme Court and its recent forays into the unfamiliar waters of patent law.
Adapted from a presentation given at the 12th Annual Biotech Patent Forum, American Conference Institute, Boston, MA, November 30, 2010.
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