Mayo Test

Mayo Collaborative Services v. Prometheus Laboratories (S.Ct. 2012) is the foundational case for patent eligibility under § 101: THE PATENT: Prometheus Laboratories held patents on methods of optimizing thiopurine drug dosages for treating autoimmune diseases (Crohn's disease, ulcerative colitis); THE CLAIMED METHOD: (1) administer a drug (thiopurine compound) to a patient; (2) measure the level of metabolites (6-thioguanine) in the patient's blood; (3) if the metabolite level is below a threshold, the dose is too low (may be ineffective); (4) if the level is above a threshold, the dose is too high (may be toxic); THE DISCOVERY: Prometheus discovered the specific numerical thresholds that correlate with drug efficacy and toxicity; this correlation is a relationship between metabolite levels and drug effectiveness; THE HOLDING (unanimous; Justice Breyer): the claims were directed to a law of nature — the relationship between thiopurine metabolite levels and patient response; the 'administer,' 'determine,' and 'wherein' steps added nothing of significance: 'administer' was a well-understood activity; 'determine' instructed routine blood testing; the 'wherein' clauses merely described the natural law correlation; together, they simply instructed practitioners to apply the natural correlation — 'apply it' is not enough; THE MAYO FRAMEWORK: Step 1: does the claim involve a law of nature, natural phenomenon, or abstract idea (a 'judicial exception')? Step 2: does the claim include elements sufficient to ensure it amounts to significantly more than a patent on the judicial exception itself?; SIGNIFICANCE: Mayo defined the current framework for all § 101 analysis; it was extended to abstract ideas in Alice (2014) and applies uniformly to software, biotech, and other fields.

Mayo dramatically curtailed patent protection for diagnostic and personalized medicine methods: THE DIAGNOSTIC PATENT CRISIS: most diagnostic method claims follow the pattern: observe a biological marker → correlate to disease state or treatment response → inform treatment decision; under Mayo, the correlation is a natural phenomenon; the observation steps are routine; the treatment decision step is generic; the result: the claim 'amounts to nothing more than an instruction to apply the natural law'; ARIOSA DIAGNOSTICS v. SEQUENOM (Fed. Cir. 2015): cell-free fetal DNA (cffDNA) in maternal blood; Sequenom discovered that fetal DNA circulates in maternal plasma — a natural phenomenon; claimed method: take maternal blood sample, amplify cffDNA, and detect paternally-inherited sequences to determine fetal characteristics; Federal Circuit held INELIGIBLE: discovery of a natural phenomenon; amplification and detection = routine conventional techniques; 'GROUNDBREAKING, TRANSFORMATIVE, OR EVEN BRILLIANT' IS NOT ENOUGH: Judge Linn concurred but noted: 'I am aware of no case more troubling than this one' — a genuinely important medical discovery was denied patent protection; Vanda Pharmaceuticals v. West-Ward Pharmaceuticals (Fed. Cir. 2018): method of treating patients with a specific SNP genotype using lower-dose iloperidone found ELIGIBLE: the key: the claim was specifically directed to a method of treatment (what dose to administer, not merely correlating genotype to toxicity risk); treatment claims are more defensible than pure diagnostic claims; WHAT SURVIVES: claims directed to methods of TREATMENT (administer a specific compound in a specific way) are more likely eligible than claims directed to correlations; claims that use natural correlations as one step in a larger non-conventional method; specific new tools for measurement (devices, not just the measurement step).

Association for Molecular Pathology v. Myriad Genetics (S.Ct. 2013) addressed whether isolated gene sequences are patent-eligible: THE MYRIAD CASE: Myriad Genetics discovered the BRCA1 and BRCA2 gene sequences that are strongly associated with hereditary breast and ovarian cancer risk; Myriad held patents on: (1) the isolated DNA sequences of BRCA1 and BRCA2 (genomic DNA); (2) cDNA (complementary DNA) synthesized from the mRNA; ISOLATED GENOMIC DNA — NOT PATENT-ELIGIBLE: the Court unanimously held that naturally occurring DNA sequences (even when isolated from the genome) are products of nature; isolation does not change the genetic information in the DNA; the information-bearing function of the gene sequence is unchanged by isolation; a naturally occurring sequence found in nature is a natural phenomenon, not a patent-eligible invention; cDNA — PATENT-ELIGIBLE: cDNA is synthesized from mRNA in the laboratory; it contains the exons (coding sequences) but NOT the introns (non-coding sequences) that appear in genomic DNA; cDNA is not naturally occurring — no organism produces this exact sequence; therefore cDNA is patent-eligible (a non-natural product created by humans); PRACTICAL IMPACT: all naturally occurring gene sequences from the human genome (and other organisms) are not patent-eligible; 20+ years of gene patents were effectively invalidated as to their genomic DNA claims; companies could still patent: cDNA sequences; primers; probes (if non-naturally occurring); applications using the sequence; MYRIAD'S LEGACY: Myriad lost its core claims on the BRCA sequences; the market for BRCA testing opened to competition; the price of BRCA genetic testing dropped significantly; SYNTHETIC BIOLOGY: synthesized DNA sequences with modifications not found in nature may be patent-eligible if structurally distinct from natural counterparts.

The Federal Circuit has struggled to draw consistent lines between eligible and ineligible biotech/diagnostic claims: ELIGIBLE: VANDA PHARMACEUTICALS (Fed. Cir. 2018): claim to a METHOD OF TREATMENT (not just a diagnostic correlation); specific patient population (specific genotype); specific drug; specific dosing regimen; court distinguished Mayo: Mayo claimed only 'an information-gathering step (determining metabolite levels)' and 'do something in light of the information'; Vanda claimed a specific treatment method; Cleveland Clinic Foundation v. True Health Diagnostics (Fed. Cir. 2019): risk assessment test claims held ineligible; but same court in later cases found similar claims eligible when the method included specific treatment steps; ENFIT LABS (Fed. Cir. 2022): assay method that used a specific sequence of steps to detect biomarkers in a non-conventional manner found eligible; INELIGIBLE: Athena Diagnostics v. Mayo Collaborative Services (Fed. Cir. 2019): method of diagnosing neurological conditions by detecting novel biomarkers (MuSK antibodies); all Federal Circuit judges acknowledged this was a troubling outcome for a genuinely useful discovery; Stanford University v. Roche Molecular Systems (different issue — ownership); GUIDANCE FOR BIOTECH DRAFTING: claim methods of TREATMENT or PREVENTION (not just diagnosis); require specific administration of a specific compound; specify patient selection + dosing + monitoring together; claim the specific combination of steps in their entirety as non-conventional; draft claims to non-naturally occurring compositions (modified sequences; cDNA; engineered proteins); include multiple fall-back claim sets at varying levels of specificity.

The Mayo/Alice framework extends to mathematical concepts and physics-based inventions: MATHEMATICAL ALGORITHMS: Parker v. Flook (S.Ct. 1978): mathematical formula for computing alarm limits in catalytic conversion process; the formula + conventional post-solution steps = ineligible; the mathematical formula itself is abstract (ineligible); adding a computer or conventional post-solution activity doesn't change the analysis; Diamond v. Diehr (S.Ct. 1981): process for molding rubber products using a computer running the Arrhenius equation; held ELIGIBLE: the claim was to a process for molding rubber using a specific equation — not just the equation; the overall process transformed physical matter; distinguished from Flook because the math was integrated into a specific physical process; CURRENT MATHEMATICAL ALGORITHM ANALYSIS: a claim reciting a mathematical formula is not automatically ineligible; the question is whether the claim uses the math as part of a specific practical application; a claim that just describes the math + apply it = ineligible; a claim that uses math to achieve a specific technical result (compression improvement, error correction, signal processing improvement) with specific technical steps = potentially eligible; PHYSICS-BASED PATENTS: claims based on discovered physical phenomena face the same analysis; Prometheus v. Mayo: the thiopurine correlations were discovered physical/biochemical phenomena; Ariosa: cell-free fetal DNA in maternal blood = discovered natural phenomenon; SENSORS AND MEASUREMENT: claims to measuring physical properties face § 101 challenges if the measurement step is the invention; if the specific new device or sensor is the invention, it is more defensible; TRANSFORMATION: physical transformations of matter are generally eligible (Bilski — machine-or-transformation test); a process that physically transforms raw materials into a different state or thing is typically patent-eligible even if it involves mathematical steps.