Mayo v. Prometheus (2012): Diagnostics and laws of nature

The Core Rule: A medical diagnostic claim is not patent-eligible merely because it states a natural biological correlation and adds routine steps such as administering a known drug, measuring a metabolite, and telling a doctor to consider the result.

1. Executive Summary

In Mayo Collaborative Services v. Prometheus Laboratories, the U.S. Supreme Court unanimously held that the diagnostic method claims at issue were not patent-eligible under 35 U.S.C. §101. The claims relied on correlations between concentrations of thiopurine-drug metabolites in a patient’s blood and the likelihood that a dose would be ineffective or cause harmful side effects. The Court concluded that the additional claim steps did not transform those natural relationships into a patent-eligible application.

The decision is a foundational authority for the law-of-nature exception to patent eligibility. It asks whether the claim adds enough beyond the natural relationship itself to amount to an inventive application, rather than using conventional steps to reserve the correlation for the patent owner.

WHY IT MATTERSA claim can be new, medically useful, and commercially valuable yet still fail §101 if its substance is a natural law combined with routine activity. Patent eligibility is distinct from novelty, non-obviousness, and enablement.

2. Case at a Glance

• Court: Citation — Supreme Court of the United States: 566 U.S. 66 (2012)
• Court: Docket — Supreme Court of the United States: No. 10-1150
• Court: Argued / decided — Supreme Court of the United States: December 7, 2011 / March 20, 2012
• Court: Opinion — Supreme Court of the United States: Justice Stephen Breyer
• Court: Vote — Supreme Court of the United States: Unanimous, 9–0
• Court: Statute — Supreme Court of the United States: 35 U.S.C. §101 — patentable subject matter
• Court: Disposition — Supreme Court of the United States: Federal Circuit reversed

3. The Medical Science Behind the Dispute

The patents concerned thiopurine drugs used to treat autoimmune conditions. After a patient takes a thiopurine drug, the body metabolizes it into chemical products called metabolites. Measuring certain metabolites in the blood can help clinicians understand how the patient is processing the drug and whether the dosage may be too low or too high.

The clinical problem

Too little effective drug exposure may mean the treatment is not working adequately.

Too much exposure, or a metabolite level associated with toxicity, may indicate a higher risk of harmful side effects.

Patients differ in how they metabolize the same medication, so a single dose may not produce the same biological result in every patient.

The patent’s key correlations

The claims described relationships between metabolite concentrations and likely treatment outcomes. As one example discussed by the Court, a level of 6-thioguanine (6-TG) above approximately 400 picomoles per 8 × 10⁸ red blood cells was associated with a likelihood of toxic side effects. The claims also described a lower threshold associated with a likelihood that the dose would be ineffective.

Important: DISTINCTIONThe Court did not hold that measuring blood metabolites is inherently unpatentable. It examined the specific claims and concluded that their conventional steps did not add enough to the natural correlations they recited.

4. Parties, Patents, and Procedural History

Prometheus Laboratories was the exclusive licensee of the patents at issue. Mayo Collaborative Services and Mayo Clinic Rochester used diagnostic tests based on those patents. In 2004, Mayo announced plans to market its own, somewhat different test. Prometheus sued, alleging infringement.

District Court — Found infringement but granted summary judgment to Mayo, concluding that the claims effectively covered natural laws or natural phenomena and therefore were not patentable.

Federal Circuit — first appeal — Reversed, reasoning that the claimed processes involved transformations of the human body or blood and met the then-used machine-or-transformation test.

Supreme Court — Bilski remand — The Supreme Court remanded for reconsideration after Bilski v. Kappos clarified that the machine-or-transformation test was not the exclusive test for §101.

Federal Circuit on remand — Again found the claims patent-eligible.

Supreme Court — 2012 — Reversed. The Court held that the claims did not add sufficient features to turn the natural correlations into patent-eligible applications.

5. The Legal Question

Do method claims become patent-eligible when they recite a natural biological correlation but add steps of administering a known drug, measuring a resulting metabolite level, and informing doctors that the level may indicate a need to adjust the dosage?

THE COURT’S ANSWERNo. The additional steps, viewed individually and as an ordered combination, were not enough to transform the claims into patent-eligible applications of the natural correlations.

6. The Governing Statute: 35 U.S.C. §101

Section 101 identifies broad categories of patentable subject matter: processes, machines, manufactures, and compositions of matter, as well as qualifying improvements. The Supreme Court has long recognized implicit exceptions for laws of nature, natural phenomena, and abstract ideas.

These exceptions preserve the basic tools of scientific and technological work for everyone. A discovery of a natural relationship can be important and valuable, but a patent cannot simply claim the relationship itself and thereby restrict others from using it in research, diagnosis, or further invention.

Eligibility is not the same as other patent requirements

• Requirement: §101 eligibility — Core question: Is the claimed subject matter within eligible categories and outside judicial exceptions? — Why it differs from Mayo: The central issue in Mayo.
• Requirement: §102 novelty — Core question: Was the claimed invention already disclosed in the prior art? — Why it differs from Mayo: A claim can be new yet ineligible.
• Requirement: §103 non-obviousness — Core question: Would the claimed invention have been obvious to a skilled person? — Why it differs from Mayo: Eligibility does not establish inventive step.
• Requirement: §112 disclosure — Core question: Are the claims adequately described, enabled, and definite? — Why it differs from Mayo: A claim may fail these rules independently.

7. The Mayo Reasoning, Step by Step

Identify the natural law — The claims relied on the relationship between metabolite concentrations and the likelihood that a thiopurine dose would be ineffective or harmful. That relationship arose from the body’s natural metabolism.

Examine the added steps — The claims included administering a drug, determining the metabolite level, and describing what the level indicated about dosage.

Assess whether the steps add a patent-eligible application — The administering step identified doctors and patients already using the drug. The determining step called for conventional measurement activity. The final step communicated the significance of the natural correlation.

Consider the steps as an ordered combination — The Court did not stop at a step-by-step checklist. It also considered whether the arrangement of the steps supplied an inventive concept. It concluded that the combination still amounted to applying the natural correlations through well-understood, routine, conventional activity.

Consider pre-emption — The claims risked tying up the underlying correlations themselves, potentially restricting doctors and researchers from using the biological relationships in their work.

KEY ANALYTICAL POINTThe question is not simply whether a claim contains human activity. The question is whether the claim adds a sufficiently specific, inventive application beyond the natural law.

8. The Claim Structure: What Each Step Did

• Claim element: Administering — Function in the method: A thiopurine drug is given to a patient with a relevant condition. — Why the Court found it insufficient: The drugs were already being used for these treatments; the step largely identified the intended audience and context.
• Claim element: Determining — Function in the method: The resulting metabolite concentration is measured. — Why the Court found it insufficient: The measurement activity was conventional and did not supply the necessary inventive application.
• Claim element: Wherein / indicating — Function in the method: The measured concentration is related to toxicity or ineffectiveness and may indicate a dosage adjustment. — Why the Court found it insufficient: This communicated the natural correlation and told the doctor to consider it; it did not add a sufficiently inventive implementation.

9. Pre-emption: Why the Court Was Concerned

Pre-emption means effectively controlling other people’s ability to use a fundamental building block of science. The Court was concerned that if the claims were allowed, researchers and clinicians could face restrictions when studying or applying the same metabolite correlations, even if they used different wording or ordinary laboratory procedures.

Natural laws are often starting points for many later discoveries.

A broad claim can restrict follow-on research if its practical reach covers the correlation rather than a particular inventive implementation.

The Court treated pre-emption risk as a reason to examine whether the additional steps genuinely narrow the claim to a patent-eligible application.

Pre-emption is not a free-standing rule that every claim affecting a natural relationship is invalid. It informs the inquiry into whether the claim, in substance, monopolizes the natural law or adds a qualifying application.

10. Relationship to Earlier and Later Supreme Court Cases

• Case: Gottschalk v. Benson (1972) — Principle: A mathematical algorithm cannot be monopolized through a claim that effectively covers the idea itself. — Connection to Mayo: Reinforces the rule against claiming fundamental tools of work.
• Case: Parker v. Flook (1978) — Principle: A post-solution activity or conventional implementation does not necessarily make a claim eligible. — Connection to Mayo: Supports scrutiny of what is added to a natural principle.
• Case: Diamond v. Diehr (1981) — Principle: A process applying a mathematical relationship in a specific industrial process can be eligible when assessed as a whole. — Connection to Mayo: Contrast: Diehr involved an integrated rubber-curing process, not merely a direction to observe a relationship.
• Case: Bilski v. Kappos (2010) — Principle: Machine-or-transformation is a useful clue, not the exclusive test for §101. — Connection to Mayo: Explains why physical measurement alone did not resolve Mayo.
• Case: Association for Molecular Pathology v. Myriad Genetics (2013) — Principle: Naturally occurring DNA is not patentable merely because it has been isolated; cDNA may differ where it is not naturally occurring. — Connection to Mayo: Applies related natural-product principles in biotechnology.
• Case: Alice Corp. v. CLS Bank (2014) — Principle: Applied a two-step framework to claims involving an abstract idea and conventional implementation. — Connection to Mayo: Extended Mayo’s analytic framework to abstract ideas.

11. The Mayo / Alice Two-Step Framework

Mayo later became a central part of the framework commonly described as the Mayo–Alice test for patent eligibility. The Court in Mayo did not present a rigid formula for every case, but later decisions use two broad questions:

Step 1 — Judicial exception — Does the claim, considered as a whole, involve a law of nature, natural phenomenon, or abstract idea?

Step 2 — Inventive concept — If it does, do the claim’s additional elements, individually or as an ordered combination, add enough to ensure the claim amounts to significantly more than the exception itself?

CAUTIONThis is a legal framework, not a guarantee that a claim is eligible if it includes a laboratory instrument, computer, or physical sample. The technical details and the claim as a whole matter.

12. Worked Examples: Weaker and More Specific Claim Concepts

Illustrative concept A — likely vulnerable

CONCEPTMeasure metabolite X in a patient’s blood and tell the doctor that a level above threshold Y indicates toxicity and a level below threshold Z indicates ineffective dosage.

Why vulnerable: the core is the natural correlation; the measurement and instruction may be routine; and the claim may effectively direct clinicians to apply the correlation without specifying a sufficiently inventive implementation.

Illustrative concept B — potentially more concrete, but not automatically eligible

CONCEPTA specifically engineered assay uses a novel reagent configuration, a defined analytical sequence, and a technically particular signal-processing method to produce a measured result.

Why it may be stronger: a claim directed to a concrete technical improvement in the assay or measurement process may be more than a statement of a biological correlation. Eligibility would still depend on the actual claim language, whether the technical features are genuinely inventive, and other patentability requirements.

Illustrative concept C — still needs careful drafting

CONCEPTUse a known laboratory test and apply the discovered correlation only to a named disease or drug class.

Why the label may not help: limiting a natural law to a particular field or patient group may not create an inventive application if the added limitation merely identifies the intended environment.

These are educational hypotheticals, not legal advice or conclusions about any actual patent application.

13. Practical Lessons for Medical-Diagnostic Patent Drafting

Claim the technical implementation, not just the discovery. — Explain what is technically new about the assay, sample preparation, reagent, instrument operation, measurement process, or data-processing technique.

Be precise about the claimed improvement. — State how the claimed steps change the operation of the diagnostic technology, not only how a result should be interpreted.

Avoid relying on routine steps as the sole inventive feature. — Administering a known drug, collecting a sample, measuring a known analyte, or advising a clinician may be insufficient when these steps merely surround the natural correlation.

Assess the ordered combination. — Eligibility analysis considers how claim elements work together, not just whether each element existed independently.

Consider claim breadth and practical reach. — Ask whether the claim could restrict use of the underlying biological relationship by doctors, laboratories, or researchers employing other methods.

Keep patent requirements separate. — A detailed technical invention must still satisfy novelty, non-obviousness, written description, enablement, and definiteness requirements.

14. What Mayo Does — and Does Not — Hold

• Mayo holds: • Natural laws themselves are not patentable. — Mayo does not hold: • All medical diagnostic tests are unpatentable.
• Mayo holds: • Routine steps that merely tell users to apply a natural correlation may not create eligibility. — Mayo does not hold: • All claims involving biomarkers or metabolite measurements fail §101.
• Mayo holds: • The claim must add enough to qualify as a genuine application. — Mayo does not hold: • Any use of a natural law is forbidden.
• Mayo holds: • Claim scope and pre-emption concerns matter. — Mayo does not hold: • Physical transformation or laboratory testing automatically establishes eligibility.

15. Ratio Decidendi

RATIOA process claim that recites a natural biological correlation is not patent-eligible under §101 when its additional steps—considered individually and as an ordered combination—amount only to well-understood, routine, conventional activity that tells relevant users to apply the correlation, rather than adding a sufficient inventive application.

16. Key Terms

• Term: Metabolite — Meaning: A substance produced when the body chemically processes a drug or other compound.
• Term: Biomarker — Meaning: A measurable biological feature that can indicate a physiological state or process.
• Term: Law of nature — Meaning: A relationship or principle arising from nature rather than a human-created invention.
• Term: Patent eligibility (§101) — Meaning: The threshold question whether the claimed subject matter falls within patentable subject matter and avoids judicial exceptions.
• Term: Pre-emption — Meaning: The risk that a claim effectively controls use of a fundamental natural principle or basic tool of science.
• Term: Ordered combination — Meaning: The claim elements considered together in the particular arrangement claimed.
• Term: Inventive concept — Meaning: Additional claim features sufficient to make the claim more than a claim to the judicial exception itself.
• Term: Machine-or-transformation test — Meaning: A useful clue in process-claim analysis, but not the sole or definitive §101 test.

17. Primary Sources and Further Reading

Official U.S. Reports case record — GovInfo https://www.govinfo.gov/app/details/USREPORTS-566/USREPORTS-566-66

Official U.S. Reports PDF — Supreme Court opinion https://www.govinfo.gov/content/pkg/USREPORTS-566/pdf/USREPORTS-566-66.pdf

Cornell Legal Information Institute — full opinion https://www.law.cornell.edu/supremecourt/text/10-1150

Supreme Court docket — No. 10-1150 https://www.supremecourt.gov/Search.aspx?FileName=%2Fdocketfiles%2F10-1150.htm

35 U.S.C. §101 — Patentable subject matter https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title35-section101&num=0&edition=prelim

18. Final Takeaway

Remember This: Mayo draws the line between discovering a natural biological relationship and inventing a patent-eligible way to use it. A diagnostic claim cannot obtain eligibility simply by pairing a natural correlation with routine testing and an instruction to consider the result.

This case study is an educational summary of the Court’s decision. It is not legal advice. For a specific patent claim, the full claim language, specification, prosecution history, and current controlling law must be reviewed.

Related patent research

AMP v. Myriad Genetics (2013): Gene patents and naturally occurring DNA

Diamond v. Chakrabarty (1980): Patenting engineered organisms

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