Master Supreme Court unanimously held that claims tying routine steps to a natural correlation are not patent-eligible under 35 U.S.C. § 101. with this comprehensive case brief.
Mayo Collaborative Services v. Prometheus Laboratories is a landmark patent-eligibility case delineating the boundary between patentable applications and unpatentable laws of nature under 35 U.S.C. § 101. The Supreme Court unanimously held that a claim reciting a natural correlation—here, the relationship between drug metabolite levels and therapeutic efficacy or toxicity—cannot be rendered patent-eligible merely by appending conventional, routine steps already practiced in the field. In doing so, the Court fortified the long-recognized exception to § 101 for laws of nature, natural phenomena, and abstract ideas, and clarified how to distinguish eligible applications from impermissible monopolies on fundamental scientific relationships.
The decision profoundly impacted the biotechnology and diagnostics industries, medical practice, and patent drafting. It also supplied the analytical template later formalized in Alice v. CLS Bank, requiring courts to (1) identify whether a claim is directed to an ineligible concept, and (2) determine whether the claim's additional elements transform it into a patent-eligible application through an inventive concept. For law students, Mayo is essential to understanding modern § 101 doctrine, the preemption rationale behind judicial exceptions, and the interplay—often tension—between eligibility and other patentability requirements.
566 U.S. 66 (2012); 132 S. Ct. 1289; 182 L. Ed. 2d 321 (Supreme Court of the United States)
Prometheus Laboratories held exclusive licenses to U.S. Patents Nos. 6,355,623 and 6,680,302, claiming methods for optimizing thiopurine drug dosing (e.g., 6-mercaptopurine and azathioprine) used to treat autoimmune conditions like Crohn's disease. Representative claims recited steps of (1) administering a thiopurine drug to a patient, (2) determining the concentration of the 6-thioguanine (6-TG) metabolite in the patient's red blood cells, and (3) wherein clauses indicating that metabolite levels below about 230 pmol per 8×10^8 red blood cells suggest a need to increase dosage, while levels above about 400 pmol per 8×10^8 suggest a need to decrease dosage to avoid toxicity. The administering and determining steps, as practiced, used standard medical treatment and conventional assay techniques known in the field. Mayo Collaborative Services (part of the Mayo Clinic) had previously purchased Prometheus's test but later announced its own test employing different thresholds. Prometheus sued for infringement in the Southern District of California. The district court granted summary judgment to Mayo, holding the claims invalid under § 101 for effectively claiming a natural law. The Federal Circuit reversed, finding the claims patent-eligible under the machine-or-transformation test. After the Supreme Court decided Bilski, it granted certiorari, vacated, and remanded. On remand, the Federal Circuit again found the claims eligible. The Supreme Court then granted certiorari and unanimously reversed, holding the claims ineligible.
Are method claims that recite a natural correlation between metabolite levels and drug efficacy/toxicity patent-eligible under 35 U.S.C. § 101 when the additional claim steps consist of well-understood, routine, and conventional activity previously engaged in by those in the field?
Laws of nature, natural phenomena, and abstract ideas are not patentable under 35 U.S.C. § 101. To be patent-eligible, a claim that involves a law of nature must include additional elements that amount to significantly more than the law of nature itself—an inventive concept that transforms the claim into a patent-eligible application. Merely appending well-understood, routine, conventional activity (or post-solution activity) to a natural law does not suffice, nor does drafting the claim in method form with generic administration or measurement steps. The machine-or-transformation test is a useful clue but not determinative. Eligibility must be assessed to avoid disproportionately tying up (preempting) the use of the underlying natural law.
No. The claims are not patent-eligible. They effectively claim a law of nature—the correlation between thiopurine metabolite levels and therapeutic efficacy/toxicity—and the additional steps of administering and determining metabolite levels are well-understood, routine, and conventional activities that do not supply an inventive concept. The Supreme Court reversed the Federal Circuit.
The Court first identified the natural law at the heart of the claims: specific relationships between thiopurine metabolite concentrations in the blood and the likelihood that a dosage will be ineffective or cause harm. Such correlations exist in nature and are not themselves patentable. The claims' other steps—administering a thiopurine drug to a patient and determining metabolite levels using known assays—were activities already practiced in the field. The wherein clauses that merely indicate a need to increase or decrease dosage upon observing certain levels do not require any concrete treatment step; they effectively tell a doctor about the natural correlation and to apply it as such. Because these steps add nothing more than well-understood, routine, and conventional activity, the claims preempt use of the underlying natural law. The Court emphasized that allowing patents to monopolize basic scientific relationships would inhibit further discovery, contrary to the objectives of the patent system. It rejected the argument that novelty or nonobviousness under §§ 102/103 should do the work here; § 101 performs a distinct gatekeeping role. Although the machine-or-transformation test can be informative, it is not controlling, and even a transformation (such as a blood test) cannot salvage a claim that, in substance, claims a natural law plus routine steps. Comparing to precedent, the Court analogized to Flook (where mathematical formula plus conventional steps was ineligible) and distinguished Diehr (where a mathematical formula was integrated into a specific, improved industrial process). Here, the claims did not improve a specific process or require unconventional steps; instead, they merely instructed practitioners to observe the law of nature and adjust treatment as appropriate, thereby risking undue preemption of future research and medical practice.
Mayo crystallized the modern § 101 framework later formalized in Alice, introducing the requirement that claims reciting ineligible concepts must include an inventive concept—something significantly more than well-understood, routine, conventional activity. It reshaped patent strategy in life sciences, particularly for diagnostic methods, and led to the invalidation of numerous diagnostic and correlation-based patents (e.g., Ariosa v. Sequenom). For law students, Mayo is foundational to understanding eligibility analysis, the preemption rationale, how to integrate scientific discoveries into patentable applications, and the persistent tension between § 101 and other patentability requirements.
A law of nature is a fundamental scientific relationship that exists independently of human action, such as the correlation between a patient's metabolite levels and the efficacy or toxicity of a drug. In Mayo, the Court identified the specific thresholds of thiopurine metabolites and their clinical implications as a natural law. Merely recognizing or articulating such a correlation is not patentable; the claim must apply it in a way that adds significantly more than conventional activity.
Mayo supplied the substantive backbone of the Alice framework. Step one asks whether the claim is directed to an ineligible concept (law of nature, natural phenomenon, or abstract idea). If so, step two asks whether the claim elements, individually and as an ordered combination, add an inventive concept—i.e., significantly more than the ineligible concept, beyond well-understood, routine, conventional steps. Alice applied this structure to abstract ideas, explicitly drawing on Mayo's reasoning.
Not necessarily. Adding a generic instruction to adjust a dose does not by itself supply an inventive concept if the adjustment is conventional. Eligibility turns on whether the claim integrates the natural law into a specific, concrete application that uses nonroutine, nonconventional steps to achieve a practical improvement. Claims that recite a particular treatment protocol, grounded in more than routine practice and tied to a concrete therapeutic improvement, may fare better, but each case is highly fact-dependent.
No. The test remains a useful clue but is not dispositive. Performing a blood draw or lab assay may constitute a transformation, yet if these steps are routine and the claim's substance is a natural correlation, eligibility fails. Mayo makes clear that compliance with machine-or-transformation cannot substitute for the requirement of an inventive concept.
No. The Court distinguished Diehr, where a mathematical formula was integrated into a specific industrial process for curing rubber, yielding an improved technological method. By contrast, Mayo's claims recited a natural correlation and appended routine, conventional steps. The key distinction is whether claim elements transform the ineligible concept into a specific, inventive application rather than merely instructing practitioners to apply the law of nature.
Post-Mayo, courts have frequently invalidated diagnostic claims that recite natural correlations plus routine steps (e.g., Ariosa Diagnostics v. Sequenom). Combined with AMP v. Myriad on gene patenting and Alice on abstract ideas, Mayo has tightened eligibility in life sciences. It has influenced claim drafting toward concrete, treatment-focused applications and spurred debates about legislative reform and the proper boundary between § 101 and §§ 102/103/112.
Mayo stands as a defining statement on patent eligibility for life-science methods: discovering a natural correlation, no matter how valuable, is not enough. Claims must integrate that discovery into a specific, inventive application that goes beyond routine and conventional steps, lest they preempt fundamental scientific tools and impede future research.
For students and practitioners, the case underscores the centrality of the inventive concept inquiry and its preemption-driven purpose. It also highlights strategic considerations in claim drafting and litigation: frame the invention as a concrete technological improvement with nonconventional implementation, and be prepared to address eligibility distinctly from novelty and nonobviousness.
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