Mayo v. Prometheus — Laws of Nature Are Not Patentable; Court Establishes Two-Step §101 Framework

Background

Prometheus Laboratories held patents on methods for optimizing the dosage of thiopurine drugs, which are used to treat autoimmune diseases like Crohn’s disease. The patents covered a method of administering the drug to a patient, measuring the resulting metabolite levels in the patient’s blood, and using correlations between those metabolite levels and treatment efficacy to determine whether to adjust the dose.

Mayo Collaborative Services, a clinical laboratory, developed its own test that used similar correlations to guide drug dosing. Prometheus sued for infringement. Mayo argued that the patents claimed laws of nature — specifically, the natural relationship between metabolite concentration and therapeutic effect — and were therefore patent-ineligible. The Federal Circuit upheld the patents, finding that the application steps satisfied the machine-or-transformation test. The Supreme Court granted certiorari and reversed.

The Court’s Holding

Justice Breyer, writing unanimously for the Court, held that Prometheus’s patents were invalid because they claimed a law of nature — the natural correlation between thiopurine metabolite levels and health outcomes — without adding anything inventive beyond the natural law itself. The Court articulated what became known as the “Mayo two-step framework” (later formalized in Alice v. CLS Bank):

First, determine whether the claim is directed to a patent-ineligible concept (a law of nature, natural phenomenon, or abstract idea). Second, examine whether the claim’s remaining elements — individually or as an ordered combination — add “enough” to transform the nature of the claim into a patent-eligible application. Simply appending conventional steps (“administer the drug,” “determine the level,” “be aware of the correlation”) does not provide the necessary inventive concept. The steps here were routine and conventional, so the patents added nothing beyond the natural law itself.

Key Takeaways

• Claims directed to natural correlations or laws of nature are patent-ineligible under §101, even when the correlation was discovered by the inventor.
• Combining a law of nature with conventional, routine steps does not create a patent-eligible invention — the additional steps must themselves add an inventive concept.
• The Court established the two-step Mayo/Alice framework for §101 analysis, which has since been applied to thousands of patent cases.
• Personalized medicine and diagnostic method patents face particular scrutiny, as they often rest on correlations between biological markers and clinical outcomes.

Why It Matters

Mayo is arguably the most consequential patent eligibility decision of the decade. By invalidating diagnostic method patents based on natural correlations, the Court set off a wave of challenges that ultimately invalidated thousands of patents in medicine, biotechnology, and software. The two-step framework the Court introduced became the template for Alice Corp. v. CLS Bank (2014), transforming §101 from a minor threshold into a major patent-killing doctrine.

The decision sparked controversy in the personalized medicine community, where companies invest heavily to discover which genetic variants, biomarkers, or drug levels predict patient outcomes. If those correlations are laws of nature, the patents covering them may be invalid — potentially reducing incentives to invest in diagnostic innovation. Congress, the USPTO, and the Federal Circuit have all grappled with the fallout from Mayo in the years since, and the debate continues today.