In Mayo Collaborative Services v. Prometheus Laboratories, Inc., the Supreme Court ruled that laws of nature are not patentable. Neither are processes that recite use of a law of nature. Drug patents are patentable if the process has additional features. These features must provide practical assurance that the process is more than merely a drafting effort designed to monopolize the law of nature.

Patent Attorney Michele Lawson Explains Mayo Decision in 10 minutes.

Background

Thiopurine drugs treat various autoimmune diseases. Patients metabolize the drugs differently, so it was difficult for doctors to determine a recommended dosage for each patient. Scientists already knew metabolite levels corresponded to the efficacy and toxicity of thiopurine drugs.

  • Azathioprine (AZA), branded IMURAN, is an immunosuppressive drug.
  • Mercaptopurine (6-MP), distributed as PURINETHOL, is used for cancer and autoimmune diseases.
  • Tioguanine, also known as thioguanine or 6-thioguanine (6-TG)
The family of thiopurine drugs are purine antimetabolites widely used in the treatment of lymphoblastic leukemia, autoimmune disorders and transplant recipients.

However it was unknown what these actual metabolite levels were for efficacy and toxicity. Mayo determined the threshold metabolite levels that corresponded to efficacy/toxicity. This made it easier for doctors to administer the proper dose of the drug to each individual patient.

At issue in the Mayo case are two patents, U.S. 6,355,623 and U.S. 6,680,302, that claimed a diagnostic tool related to calibrating the dose of thiopurine drugs based on metabolite levels. An exemplary claim from U.S. Patent No. 6,355,623:

1.         A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising:

(a) administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and

(b) determining the level of 6-thioguanine in said subject having said immune-mediated gastrointestinal disorder,

wherein the level of 6-thioguanine less than about 230 pmol per 8×108 red blood cells indicates a need to increase the amount of said drug subsequently administered to said subject and

wherein the level of 6-thioguanine greater than about 400 pmol per 8×108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject

Supreme Court Opinion

The Supreme Court found the claims ineligible. It held that laws of nature are not patentable. The Court reasoned that the claims do nothing more than simply describe the natural relationships between the concentrations of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm. The Court took note of the fact that at the time of the invention, scientists already knew that metabolite levels of thiopurine drugs in a patient’s blood correlated with efficacy/toxicity. However, the precise correlations were unknown. The Court summarized the claim as follows:

Administer doses of thiopurine drugs, then

  1. Measure (somehow) the current level of the relevant metabolite;
  2. Use particular (unpatentable) laws of nature (which the claim sets forth) to calculate the current toxicity/inefficacy limits; and
  3. Reconsider the drug dosage in light of the law of nature

The Court looked to see “whether the claims do significantly more than simply describe these natural relationships”, finding that they did not. The claimed steps, as well as the combination of steps, were only well-understood, routine, and conventional activity previously engaged in by researchers in the field. The claim failed to enumerate a specific amount of drug. Furthermore, the claim failed to enumerate any added steps to take as a result of the “indication” of a need to increase or decrease. Thus, the Court found the claim still infringed even if a subsequent treatment plan did not change.

Justice Stephen Breyer
Justice Stephen Breyer delivered the opinion for a unanimous Court.

Unpatentable Law of Nature

The Court also found that the underlying subject matter claimed an unpatentable law of nature. Specifically, the natural correlation between efficacy and the concentration of drug metabolite in the patient’s blood. The Court conceded the claims require human action, i.e. the administration of a thiopurine drug. This triggers the relation in a person. The relation is a mere consequence of the ways in which the body metabolizes thiopurine compounds. This is an entirely natural process. Anyone who wants to make use of these laws must first administer a thiopurine drug and measure the resulting metabolite concentrations. Thus, the claims are essentially just requiring one to apply the law.

Takeaway from Mayo

Laws of nature are not patentable, and neither are processes reciting a law of nature unless that process has additional features that amount to significantly more than just describing the natural relationships.

Avoid “Determining.”

In drafting claims in light of Mayo, it is important to not use a “determining” step with highly general language that covers all processes making use of a correlation, including later discovered processes that measure levels in new ways.

Use “Administering” Step.

An “administering” step often represents sufficient human action to overcome a potential 101 rejection. In this case the “administering” step simply helps pick out the group of individuals likely interested in applying the law of nature. It did not represent “significantly more” than the law itself.

The Claim Preamable

The preamble is important into determine if the claim is “directed to” a law of nature. Pure diagnostic claims are unlikely to be patent eligible under 101 if they are relying on a natural relationship, i.e. are “directed to” a natural relationship, without significantly more. Method of treatment claims are more likely to be patent eligible under 101, particularly if they are directed to a specific population, specific treatment, and specific outcome.