Myriad Stands: Bizarre Logic and Dire Consequences

September 14, 2012

By Eugene Sisman

On August 16 2012, the Federal Circuit once again ruled on Association for Molecular Pathology v. U.S.P.T.O., the so called Myriad case.¹ The U.S Supreme Court vacated that court’s earlier decision to uphold the patentability of isolated DNA encoding breast cancer type 1 susceptibility protein (“BRCA1”) and breast cancer type 2 susceptibility protein (“BRCA2”) in light of Prometheus,² which reiterated that methods merely applying natural laws are not patentable subject matter. While the latest Myriad decision ruled on a compelling tit-for-tat regarding the headline issue, the patentability of isolated naturally occurring genes,³ the real drama and the potential watershed occurs later in the decision and with little ado.⁴

In less than three pages Federal Circuit Judge Lourie dismissed the idea that the Supreme Court’s Prometheus holding regarding patentable subject matter bars a method for discovering anti-cancer therapeutic agents comprising the steps of:

culturing a cell spliced with BRCA1
dosing the cell culture with drug candidates
comparing the rate of cell proliferation to a control group with no drug candidate and surmising that compounds inhibiting the growth of BRCA1 cells have anti-cancer properties.⁵

The justification for patentability, according to Judge Lourie, appears to be that the cell used in the assay is man-made; it is spliced with BRCA1 and does not naturally express the gene. But, the purpose of the method was, in essence, to determine whether a given chemical compound was a potential anti-cancer therapeutic. This ruling utterly misapplies Prometheus.

In Prometheus, the Supreme Court invalidated method claims for optimizing therapeutic doses of 6-methyl-mercatopurine (“6-MMP”) and 6-thioguanine (“6-TG”) to treat an immune-mediated gastrointestinal disorder as unpatentable subject matter.⁶ The method instructed practitioners to

dose a subject with a compound;
measure the concentration of compound metabolites in the subject’s blood;
apply a known formula to extrapolate the concentration of the drug; and
increase the dose if the concentration fell below a known effective concentration or decrease the dose if the subject exhibited a blood concentration in the known toxic range.⁷

The Court reasoned that the method did no more than apply natural laws regarding drug dose to blood concentration conversions. To let a patent stand that effectively applied known effective doses and known toxic doses would be to allow an impermissible patent on the underlying natural laws.⁸

The Prometheus Court illustrated the problem by comparing the patent before it to a patentable method applying a natural law in Diehr.⁹ There, a method claim for curing rubber applied the Arrhenius equation, a natural law, in conjunction with a rubber mold with an internal thermometer connected to a computer preprogrammed to open the mold under certain conditions.¹⁰ The Court in Diehr reasoned that the method was patentable because it resulted in a specific physical transformation, a “function which patent law was designed to protect.”¹¹ The key distinction appears to be whether the method utilizing a natural law results in a transformation, as in Diehr, or a mere gathering of information, as in Prometheus. Note also that while the drug dosing information gathered in Prometheus is presumably intended to eventually affect a physical transformation in a human subject suffering from a medical condition, the claim itself is directed to a method for obtaining a piece of information. The physical transformation in Diehr, by contrast, is the object of the claim. Given a choice between the two, the drug screen method claim in Myriad much more closely resembles the dose determination in Prometheus than the method for rubber molding in Diehr.

The Federal Circuit justified its decision on the ground that the man-made cell spliced with BRCA1 made patentable an application of a natural law where the same screen with a naturally occurring cell would be unpatentable. But this too is a misapplication of the Prometheus Court’s comments on Diehr. The focus of the test is whether the method creates a transformation, not whether the method utilizes a component that has previously been the subject of a transformation.

To put it another way, the Supreme Court in Prometheus has declared that it is a mere application of natural laws to determine the volume of a rock by dunking it in a graduated container of water and measuring the increase in water level because doing so would merely apply Archimedes’ Principle. The Federal Circuit has effectively responded by saying that repeating the same process with a cellular phone instead of a rock is patentable subject matter because the phone is patentable subject matter. Surely the Federal Circuit can do better.

¹Ass’n for Molecular Pathology v. U.S.P.T.O., No. 2010-1406 (Fed. Cir. Aug. 16, 2012).

²Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 132 S. Ct. 1794 (2012) vacating 653 F. 3d 1329 (Fed. Cir. 2011); Mayo Collaborative Services v. Prometheus Labs., 132 S. Ct. 1289 (2012).

³No. 2010-1406, at 38-55 (ruling that isolated DNA falls within patentable subject matter under 35 U.S.C. § 101 as a composition of manmade matter because it does not exist in an unwound state and as a molecule separate from its underlying chromosome in nature and that, via the hand of man, it is “manipulated chemically so as to produce a molecule that is markedly different from that which exists in the body”).

⁴Id. at 59-62 (ruling that the method claims pertaining to cancer drug screens are patentable subject matter under Prometheus because they involve a component that is patentable composition of matter).

⁵Id.; U.S. Patent No. 5,747,282 (filed June 7, 1995).

⁶132 S. Ct. 1289; U.S. Patent No. 6,680,302 (filed Dec. 27, 2001); U.S. Patent No. 6,355,623 (filed Apr. 8, 1999). The Court’s exemplary claim was: “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.” (132 S. Ct. 1289 at 1295.)

⁷U.S. Patent No. 6,355,623 (filed Apr. 8, 1999).

⁸132 S. Ct. 1289 at 1305.

⁹Id. at 1298.

¹⁰Diamond v. Diehr, 450 U.S. 175 (1981).

¹¹Id. at 192.