Background
Prometheus Laboratories held patents claiming methods for optimizing the dosage of thiopurine drugs — used to treat autoimmune diseases and certain cancers — by measuring the concentrations of thiopurine metabolites in a patient’s blood. The claimed methods involved administering the drug to a subject, measuring specific metabolite levels, and comparing those levels to specified ranges to determine whether the dose should be increased or decreased. Mayo Collaborative Services, a medical testing company, performed similar metabolite testing services and argued the patents were invalid as covering unpatentable natural phenomena or mental steps.
The district court invalidated the patents under § 101, finding that the claimed methods covered nothing more than relationships between drug metabolites and clinical outcomes — natural phenomena that existed independently of the patent. Prometheus appealed, and the Federal Circuit initially resolved the case using the machine-or-transformation test, remanding after the Supreme Court’s Bilski decision for reconsideration of that framework.
The Court’s Holding
The Federal Circuit again upheld the patents. On the Bilski-remanded question, the court applied the machine-or-transformation test as a useful guide — not the sole test — for § 101 eligibility. The claimed methods satisfied transformation: the step of administering thiopurine drugs to a human subject and then measuring specific metabolite levels in blood or tissue constituted a genuine physical transformation of matter. The metabolite measurement steps involved chemical transformation of the patient’s blood sample, not mere observation of a naturally occurring phenomenon in an untransformed state.
The court distinguished the patents from claims that merely recite a law of nature or natural phenomenon: Prometheus’s claims required active steps — administering the drug, measuring the metabolite — that together constituted a method of treatment optimization, not simply an observation of a pre-existing bodily state. The “wherein” clauses setting forth the metabolite threshold ranges correlated to toxicity were not mere mental steps but functional limitations tied to the physical transformation.
Key Takeaways
- Diagnostic method claims can be patent-eligible under § 101 when they involve active steps that transform physical matter — such as administering a drug and measuring resulting metabolite concentrations — rather than merely observing a natural phenomenon.
- The machine-or-transformation test, while not the exclusive § 101 standard after Bilski, remains a useful tool for evaluating method claim eligibility, particularly for process claims involving physical transformations.
- Correlation claims (“measuring X, wherein if X is high, consider increasing dose”) can survive § 101 if the measuring step itself involves physical transformation — but are vulnerable if the physical steps are regarded as mere data-gathering prelude to a mental process.
- This decision was subsequently reversed by the Supreme Court in Mayo Collaborative Services v. Prometheus Laboratories (2012), which held that claims directed to natural laws — even when accompanied by administering and measuring steps — are not patent-eligible.
Why It Matters
The Federal Circuit’s 2009 Prometheus decision represented the high-water mark of diagnostic method patent protection before the Supreme Court’s landmark 2012 reversal. At the time, the ruling gave pharmaceutical and biotechnology companies confidence that patents on personalized medicine methods — tying drug dosages to patient-specific biomarker measurements — were patent-eligible as transformation-based process claims.
The Supreme Court’s 2012 reversal fundamentally changed that calculus, holding that the natural relationship between metabolite levels and clinical outcomes could not be patented by appending routine administering and measuring steps. The Prometheus saga — both the Federal Circuit’s affirmances and the Supreme Court’s reversal — became one of the defining battles over the patent-eligibility of diagnostic and personalized medicine technologies, with consequences that continue to shape biotechnology patent strategy today.