In the United States, inventors can obtain a patent for "any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof . . .,"1 so long as the patent does not attempt to claim any of the three judicially created exceptions: "laws of nature," "physical phenomena,"and "abstract ideas." The Supreme Court, however, has done little over the years to provide further insight into the scope of these exceptions let alone articulate clear tests for patent-eligible subject matter. On March 20, 2012, the U.S. Supreme Court issued its much-anticipated decision in Mayo Collaborative Services v. Prometheus Laboratories, Inc. ("Prometheus"),2 unanimously holding that Prometheus's claims, directed to methods for optimizing the efficacy of a drug, are directed to laws of nature and, consequently, not patent eligible under 35 U.S.C. § 101. Unfortunately, Prometheus merely muddied the landscape adding further confusion to the patentable subject matter analysis. Moreover, Prometheus has left many wondering what is the fate of patents directed towards methods in the fields of diagnostic testing, personalized medicine, and biotechnology. The authors attempt to shine some light on the practical insights one can glean from Prometheus. We also look at the impact of the decision on the continuing saga of Association for Molecular Pathology v. U.S. Patent and Trademark Office ("Myriad"), where the Supreme Court granted certiorari and remanded to the Federal Circuit for reconsideration in view of Prometheus.
The patents-at-issue in Prometheus relate to methods of optimizing therapeutic efficacy and reducing toxicity when using thiopurine drugs to treat autoimmune diseases, such as Crohn's disease and ulcerative colitis. Because patients metabolized thiopurine drugs differently, the same dose of the drug affects different patients differently, and it has been difficult for doctors to determine whether for a particular patient a given dose is too high, risking harmful side effects, or too low, and so likely ineffective. At the time of filing of the Prometheus patents, scientists already understood that the levels of certain metabolites in a patient's blood were correlated with the likelihood that a particular dosage could cause harm or prove effective, but the precise correlations were not known. Prometheus is the sole and exclusive licensee of the patents-at-issue and has been selling diagnostic tests that embody the claimed processes. The following claim was used by the courts to exemplify the patented processes:
A method of optimizing therapeutic efficacy for treatment of an immune-mediated gastrointestinal disorder, comprising:
- administering a drug providing 6-thioguanine to a subject having said immune-mediated gastrointestinal disorder; and
- 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 8x108 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 8x108 red blood cells indicates a need to decrease the amount of said drug subsequently administered to said subject.
Mayo Clinic Rochester and Mayo Collective Services (collectively "Mayo") initially bought and used the diagnostic tests, but in 2004, announced that it intended to begin using and selling its own test. Prometheus subsequently brought suit.
Prometheus was initially decided by the United States District Court for the Southern District of California ("the Trial Court"). The Trial Court held that the patents-at-issue were invalid under § 101, finding that the correlations between metabolite levels and drug toxicity or efficacy are natural phenomena and that the claims would wholly preempt this natural phenomena because they cover the correlation itself.3 The Federal Circuit reversed the Trial Court's ruling on September 16, 2009, holding that the claimed "administering" and "determining" steps satisfied the "machine or transformation" test.4 Mayo petitioned for certiorari, and the Supreme Court vacated the Federal Circuit's decision on June 29, 2010, and remanded for reconsideration in light of Bilski v. Kappos.5 On remand, the Federal Circuit reaffirmed its earlier decision on December 17, 2010, again holding that the "machine or transformation" test was met and, thus, the claims do not encompass laws of nature or preempt natural correlations.6 The Supreme Court disagreed, concluding that Prometheus's claims do nothing more than simply describe the natural relationships between concentrations of certain metabolites in the blood and the likelihood that a dosage of a thiopurine drug will prove ineffective or cause harm.
- Patent-Eligible Methods Must Have an "Inventive Concept"
Writing for the Court, Justice Breyer began his analysis by noting that this case "lies at the intersection" of the Court's basic principles that that "‘laws of nature, natural phenomena, and abstract ideas' are not patentable" and "to transform an unpatentable law of nature into a patent-eligible application of such a law, one must do more than simply state the law of nature while adding the words 'apply it.'"7 Patent-eligible claims must include an "inventive concept"that goes beyond the natural law itself. Justice Breyer writes: "a process that focuses upon the use of a natural law [must] also contain other elements or a combination of elements, sometimes referred to as an'inventive concept,' sufficient to ensure that the patent in practice amounts to significantly more than a patent upon the natural law itself."8 Specifically, the Court explained that a process reciting a law of nature must have "additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself."9 The Court, however, did not provide any further specific guidance in its opinion as to what types of additional features and the inventive level required to impart patentability.
Analysing Prometheus's claims, Justice Breyer explained that while the "administering," "determining," and "wherein" steps are not themselves natural laws, they are not sufficient to transform the nature of the claim. "Beyond picking out the relevant audience, namely those who administer doses of thiopurine drugs, the claim simply tells doctors to: (1) measure (somehow) the current level of the relevant metabolite, (2) use the 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."10
The Court then compared the claim to the Court's past precedent in Diamond v. Diehr11 and Parker v. Flook.12 In Diehr, the Court held that a method for molding raw, uncured rubber into various cured, molded products was patent eligible since while the process used the Arrhenius equation to determine when to open the press, the claimed method integrated the equation into the process as a whole. Specifically, the claimed process included the "steps of'installing rubber in a press, closing the mold, constantly determining the temperature of the mold, constantly recalculating the appropriate cure time through the use of the formula and a digital computer, and automatically opening the press at the proper time,'"13 none of which were obvious, already in use, or purely conventional. The Court also noted that the claimed method did not attempt to pre-empt use of the equation.
In contrast, the Court in Flook held that a method for adjusting "alarm limits" in the catalytic conversion of hydrocarbons was not patentable because the claimed process did "nothing other than'provide a[n unpatentable] formula for computing an updated alarm limit.'"14 There, the claimed process amounted to an improved system involving the well-known steps of (1) measuring certain operating conditions, (2) using a mathematical algorithm to calculate the current alarm limits, and (3) adjusting the system to reflect the new values. "Unlike the process in Diehr, it did not 'explain how the variables used in the formula were to be selected, nor did the [claim] contain any disclosure relating to chemical processes at work or the means of setting off an alarm or adjusting the alarm limit.'"15 Finding Prometheus's case to be weaker than Diehr and no stronger than Flook, the Court concluded that the claims provide "instructions" that "add nothing specific to the laws of nature other than what is well-understood, routine, conventional activity, previously engaged in by those in the field."16
Moreover, the Court was also concerned that the patents were so broad that they would improperly tie up the future use of the claimed law of nature and potentially inhibit future scientific discovery. According to the Court, the patents not only tie up the doctor's subsequent treatment decision whether that treatment does, or does not, change in light of the interferences he has drawn using the correlations, but also threaten to inhibit the development of more refined treatment recommendations that combine Prometheus's correlations with later discovered features of metabolites, human physiology, or individual patient characteristics. The Court also concluded that the claimed "determining" step was too general and covered all processes that measure metabolites in new ways.
In reaching its decision, the Court rejected several arguments in support of Prometheus's position. First, the Court explained that while the Federal Circuit's "machine or transformation" test is "an 'important and useful clue' to patentability," the Court has "neither said nor implied that the test trumps the 'law of nature' exclusion" and that the test fails in this case.17
Second, in response to Prometheus's argument that because the particular laws of nature that its claims embody are narrow the patents should be upheld, the Court concluded that its past precedent "[has] not distinguished among different laws of nature according to whether or not the principles they embody are sufficiently narrow" and that "the cases have endorsed a bright-line prohibition against patenting laws of nature, mathematical formulas and the like" because courts and judges "are not institutionally well suited to making the kinds of judgments needed to distinguish among different laws of nature."18
Third, in response to the government's argument that virtually any step beyond a statement of law of nature itself should transform an unpatentable law of nature into a potentially patentable claim sufficient to satisfy § 101 and that invalid claims would be weeded out by the other provisions of the patent law, the Court explained that this approach would make the "law of nature" exception to § 101 a "dead letter" and is not consistent with its past precedent in Bilski, Diehr, Flook, and Benson.19 Moreover, the Court reasoned that shifting the patent-eligibility inquiry entirely to §§ 102, 103, and 112 "risks creating significantly greater legal uncertainty, while assuming that those sections can do work that they are not equipped to do."20 The Court, however, explicitly acknowledged that in evaluating the significance of any additional steps claimed in a given process, the § 101 patent-eligibility inquiry could sometimes overlap with criteria such as § 102 novelty. While the Court's reliance of the concepts of novelty and obviousness when assessing eligibility under § 101 creates a confusing standard, it may provide another approach for differentiating future claims from the Prometheus claims.
Fourth, in response to the policy argument that a principle of law denying patent coverage here will inhibit medical research, particularly in the diagnostic area, the Court declined to determine "whether, from a policy perspective, increased protection for discoveries of diagnostic laws of nature is desirable," recognizing that it is "the role of Congress [to craft] more finely tailored rules where necessary."21
- Implications of Prometheus
While the Court's decision arguably provides very little practical guidance, clearly there are lessons to be learned. At a minimum the decision represents a shift in the law on patent-eligible subject matter under § 101. Unfortunately for practitioners, its impact will only be fully understood as the Federal Circuit and other U.S. courts move forward and apply Prometheus to pending and existing claims.
Moving forward, when assessing a claim for patent-eligible subject matter under § 101, the particular law of nature, the novel and nonobvious nature of the steps applying the law of nature, and the breadth and field of the claim are all likely relevant factors that will be considered by the USPTO or a court when determining whether a claimed method is patent-eligible subject matter. As the Court emphasized, adding the words "apply it" are not sufficient. The claim must include an inventive concept that goes beyond the law of nature. Thus, while the convolution of inventiveness with eligible subject matter may be confusing, it nonetheless is the nugget of guidance we must wrestle with moving forward.
The Court also makes clear that reliance on the "machine or transformation" test does not guarantee that a patentee or applicant may overcome a § 101 challenge. While the Court did not outright reject the Federal Circuit's "machine or transformation" test, the Court concluded that it failed in this case. The Court found the first transformation‒the "administering" step‒to be irrelevant since it simply identifies the relevant group of individuals who are likely interested in applying the law of nature. And even though the second transformation‒the "determining" step‒required taking a blood sample, the Court noted that it "could be satisfied without transforming the blood, should science develop a totally different system for determining metabolite levels that did not involve such a transformation."22 According to the Court, these steps "add nothing of significance to the natural laws themselves."23 Thus, practitioners need to draft claims that are confined to a specific, useful application of the law of nature. The safest position will be claims that clearly emphasize the novel and nonobvious aspect that is applied to the law of nature. More should be added to the law of nature other than what is well-understood, routine, and conventional activity. The drafter must also take heed that a claim is not overly broad and instead focus on additional features that do not "monopolize the law of nature itself."
In response to Prometheus, the United States Patent and Trademark Office ("USPTO") issued interim guidance on March 21, 2012.24 In that guidance, the USPTO did not provide any additional rules or tests beyond the general principles discussed by the Supreme Court. The guidance instructed its examiners to continue to use the Interim Bilski Guidance, issued July 27, 2010,25 factoring in the following considerations: (1) ensure that claims, particularly process claims, do not amount to a monopoly on the law of nature, natural phenomenon, or abstract idea itself and (2) a claim that includes an exception should include other elements or combination of elements such that, in practice, the claimed product or process amounts to significantly more than a law of nature, a natural phenomenon, or an abstract idea with conventional steps specified at a high level of generality. The USPTO noted that if a § 101 rejection is made by an examiner, the applicant can then respond to explain why the claim is not drawn solely to the exception and point to the limitations in the claim that apply the law of nature, natural phenomena, or abstract idea.
- Will Isolated DNA Remain Patent-Eligible Subject Matter?
After deciding Prometheus, the Supreme Court subsequently granted certiorari in Association for Molecular Pathology v. Myriad Genetics on March 26, 2012, and remanded the case back to the Federal Circuit to reconsider its decision in light of Prometheus. As we discussed in our article "The Myriad Scare: Isolated DNA Molecules Remain Patent Eligible (for now!),"published in the September 2011 edition of the CIPA Journal, the Federal Circuit had originally held that two methods of detecting BRCA mutations by either "analyzing" or "comparing" DNA sequences to be patent ineligible as directed to abstract mental processes, but that the claims directed towards isolated DNA molecules and a "screening" method patent eligible.26 This "screening" claim recites several steps, including steps of (1) growing host cells under certain conditions, (2) determining their growth rate, and (3) comparing those rates.27 Because the first two steps are transformative, involving "physical manipulation of the cells," and those steps are "central to the purpose of the claimed process," the Federal Circuit found they were not so abstract that they claimed only a scientific principle, and held the claim patent eligible.28
On remand, unless the Federal Circuit decides to take the case en banc, the case will be decided by the same panel who decided the initial appeal—Judges Lourie, Moore, and Bryson. How the Federal Circuit will rule on remand is uncertain, but the case has important implications not only for the patent eligibility of isolated DNA, but more generally for purified natural products and other inventions based on naturally occurring biological methods. In the Federal Circuit's original decision, Judges Lourie and Moore found Myriad's isolated BRCA1 and BRCA2 DNA molecules—which are used to test for a higher risk for breast cancer—are patentable subject matter. Judge Bryson dissented, finding cDNA sequences, which are not found in nature, are patent eligible, but finding any DNA with a chromosomal counterpart is not.
Writing for the majority, Judge Lourie explained that "[t]he distinction, therefore, between a product of nature and a human-made invention for purposes of § 101 turns on a change in the claimed composition's identity compared with what exists in nature."29 The question is whether a composition—even if altered from its natural state—has "similar characteristics" as its natural counterpart, or whether as a result of human intervention the composition has "markedly different" or "distinctive" characteristics.30 Since naturally occurring DNA sequences would seem to fall into the category of natural phenomena, the Federal Circuit will now need to consider whether the level of human intervention in "isolating" DNA is sufficient to find the claim to be a patent-eligible "application" of the phenomenon. All three judges had agreed that cDNAs, which have a completely different nucleotide sequence than cellular RNA and are the creation of man, are patent eligible, but disagreed whether isolated DNA molecules whose sequences are found on chromosomes are patent eligible.
Lourie noted that such molecules can be synthesized (either recombinantly or chemically). Thus, "isolated DNAs" are not necessarily purified in the strictest sense. He also repeatedly emphasized that such DNAs are different from chromosomal sequences because they have different chemical structures: the isolated molecules (even for very large genes) are significantly smaller than chromosomes, and they have different chemical bonds.31 For example, BRCA1 itself is about 80,000 nucleotides, but the native BRCA1 gene is found on chromosome 17, which has about 80 million nucleotides. To Lourie, this chemical difference was sufficient to render the isolated genes patent eligible.
In her concurring opinion, Moore, however, required a "significant new utility as compared to nature" to find a composition patent eligible.32 Compared to genomic sequences, the claimed DNAs have structural differences at their two ends (with a 5' hydroxyl group and a 3' phosphate group, instead of another nucleotide at each end), are substantially smaller than the same sequence found within a chromosome, and are created by man by either synthesis or by "chemically altering the larger polymer to cleave off adjacent portions."33 For the utility of isolated DNA molecules, Moore found that by removing other "potentially confounding"sequences found in the chromosome, the isolated DNAs have additional utility, "particularly for the smaller isolated fragments," which are useful as probes and primers.34 For longer isolated DNA molecules that are unsuitable for use as primers and probes, Moore stated that these longer DNAs "do not clearly lead to significant new utility as compared to nature,"35 but ultimately found that settled expectations, including the property rights of the owners of thousands of issued patents with isolated DNA claims, "tip the scale in favor of patentability."36
Judge Bryson dissented from the majority, dismissing the significance of chemical differences between an isolated DNA molecule and its native chromosomal sequence.37 Bryson characterizes the structural differences as "irrelevant to the claim limitations"38 as well as their utility as isolated DNA, stating "there is no magic to a chemical bond. . . ."39 Instead, he characterizes the isolated DNAs as simply "purified" molecules which do not acquire patentability by virtue of being extracted from their natural setting.
Thus, for patent practitioners, like a bad horror movie from the 80s, the Myriad scare is back again—stay tuned!
With the Prometheus decision, the U.S. Supreme Court has ruled that processes applying laws of nature, natural phenomena, or abstract ideas must include "additional features"that constitute "an inventive concept"in order to be patent eligible. How broadly the Court's decision will reach and whether the patent eligibility of isolated DNA molecules will be upheld in the Myriad case remains to be seen.
This article was originally printed in CIPA Journal.