As the biotechnology community awaits the Federal Circuit’s decision in the Myriad Genetics patent litigation, attention has focused on the fundamental issue in that case: whether genes and methods for interpreting mutations are patentable subject matter under section 101 of the Patent Act—that is, whether they are the kinds of things that can be patented assuming that all of the other requirements of the Patent Act (pdf) are satisfied.
However, we have argued in several articles (see, e.g., here, here and here) that the real action is more likely to involve all of those “other requirements” as courts explore other ways to limit the patentability of scientific and technology progress without altering the threshold test of patentability under section 101.
A recent Federal Circuit case (Billups-Rothenberg, Inc. v. Associated Regional and University Pathologists, Inc.) decided under the written description requirement of section 112 illustrates this point yet again.
Billups v. ARUP Background. The Billups case involves a disorder called Type I hereditary hemochromatosis, which is characterized by excessive absorption of iron. The critical gene in the absorption process is called HFE, or “High Fe.” In 1994, Billups filed the application that led to a patent on methods for testing for hemochromatosis (U.S. patent number 5,674,681; “’681”). The court’s opinion reproduces this claim as “representative”:
2. A method to identify an individual having or predisposed to having hemochromatosis, comprising the steps of:
a) providing from the individual a sample containing a gene encoding a nonclassical MHC class I heavy chain
b) detecting a mutation in said gene, which mutation results in the reduced ability of said heavy chain to associate with said β2 microglobulin, wherein the presence of said mutation identifies said individual as having or predisposed to having hemochromatosis.
Significantly, at the time of the 1994 filing Billups had not yet isolated the relevant gene or mutation—later discovered to be C282Y.
Then, in 1996, a competing research team filed a patent application that disclosed C282Y and another relevant mutation called S65C (resulting in patent number 6,025,130; “’130”). That patent was assigned to Bio-Rad Laboratories, Inc. (a co-defendant along with ARUP in this case), which in turn licensed the patent to ARUP (like Myriad Genetics, a University of Utah spinoff).
Both ARUP and Billups continued their work. ARUP developed its own hemochromatosis test that detected C282Y and S65C, and in 1999 Billups filed another patent application that resulted in patent number 6,355,425 (“’425”). The 425 patent is far more specific than the earlier ‘681 patent, disclosing the S65C mutation.
Claim 1 of the ‘425 patent reads:
A method of diagnosing an iron disorder or a genetic susceptibility to developing said disorder in a mammal, comprising determining the presence of a mutation in exon 2 of an HFE nucleic acid in a biological sample from said mammal, wherein said mutation is not a C→G substitution at nucleotide 187 of SEQ ID NO: 1 and wherein the presence of said mutation is indicative of said disorder or a genetic susceptibility to developing said disorder.
In 2009, Billups sued ARUP and Bio-Rad, claiming that the company’s “diagnostic assays or kits for detecting hemochromatosis” infringed both the ‘681 and ‘425 patents. A California federal district court found both of the Billups patents invalid and, last month, the Federal Circuit affirmed unanimously. (Judge Kimberly Moore, who is on the Myriad panel, was one of the three judges who signed the opinion in this case.)
More Nibbling Around the Ages of Patentability. According to the Federal Circuit, the problem with the ‘681 patent issued to Billups was a failure to satisfy the written description requirement of section 112. The applicant must describe the claimed invention at a sufficient level of detail to “enable any person skilled in the art to which it pertains” to make and to use the invention. (The standard is purely theoretical: that person couldn’t actually reproduce the invention, of course, because that would be infringement.) Providing an adequate written description satisfies the applicant’s part of the basic patent bargain—trading knowledge for exclusive rights—and also proves that applicant actually possesses the claimed invention.
In a series of cases, most importantly last year’s en banc decision in Ariad Pharms., Inc. v. Eli Lilly & Co., the Federal Circuit appears to have tightened the section 112 requirement for gene-related inventions. As the court put it in 1997 (in Regents of the Univ. of Cal. V. Eli Lilly & Co.), and reiterated last month in Billups:
[A]n adequate description of a DNA requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it; what is required is a description of the DNA itself.
That is, the patent must disclose not only the function of the relevant DNA, but something about its structure as well. The ‘681 patent failed this test according to the Federal Circuit:
The ’681 patent claims a test for mutations, yet it is undisputed that the specification and originally filed claims of the ’681 patent disclose neither the hemochromatosis gene sequence nor any specific mutations within that gene.
Billups contended that its written description should be judged in light of “knowledge outside the patent, including the subsequent discovery of C282Y,” but the court disagreed:
Given the lack of knowledge of sequences for the hemochromatosis gene and its mutations in the field, the limited extent and content of the prior art, and the immaturity and unpredictability of the science when the ’681 patent was filed, Billups cannot satisfy the written description requirement merely through references to later-acquired knowledge.
After dispensing with the ‘681 patent, the Federal Circuit then invalidated Billups’ ‘425 patent (filed in 1999) under section 102 as “anticipated,” or fully disclosed, by ARUP’s ‘130 patent (filed in 1996). Billups argued that the ‘130 patent’s disclosure of the S65C mutation should not count because ARUP did not appreciate its significance. The court acknowledged that “the ’130 patent discounts the utility of the S65C mutation in diagnosing hemochromatosis,” but nonetheless “held that a ‘reference [to another invention, in this case the S65C mutation] is no less anticipatory if, after disclosing the invention, the reference then disparages it.’”
These holdings may be highly technical in patent law terms, but the underlying point seems straightforward: Yet again, the Federal Circuit has demonstrated skepticism about a gene-related patent, and a willingness to scrutinize it closely under all of the requirements of the Patent Act, not just section 101.
While the question of patentable subject matter under section 101 may be more glamorous, particularly in the context of Myriad’s gene patents, it continues to appear that the real work of limiting product and method claims on genes and their interpretation is being done elsewhere.
Murky Methods. Meanwhile, back within section 101, the difficulty in figuring out the standards for the patentabilty of methods and processes was on display in two oral arguments at the Federal Circuit during the first week of May. (CyberSource Corp. v. Retail Decisions Inc., No. 2009-1358, argued 5/2/11, and DealerTrack Inc. v. Huber, No. 2009-1566, argued 5/4/11). The cases involved computer-aided manipulation of credit information, not genes, but the arguments nonetheless underscored the problems the court faces in sorting out the method claims in Myriad.
As the GLR has reported, last summer’s Bilski Supreme Court decision shed little light on the patentability of a range of emerging technologies, particularly in the areas of software and biotechnology, including the so-called “diagnostic method” patents challenged in Myriad. The Bilski Court held that the Federal Circuit’s machine-or-transformation test should not be used exclusively, but said little else beyond emphasizing that abstract ideas were unpatentable.
Since Bilski, the Federal Circuit has upheld the patentable subject matter status of a “method for the halftoning of gray scale images” on computer screens (Research Corporation Technology, Inc. v. Microsoft Corporation) and reaffirmed its earlier opinion that a method for administering a drug was also patentable subject matter (Prometheus v. Mayo). Although both cases suggest that the patentable subject matter standard is not especially demanding, neither does much to clarify exactly what that standard is.
The CyberSource patent claims a three-step method for “for verifying the validity of a credit card transaction over the Internet,” as well as a “computer readable medium” programmed to carry out the method (a so-called Beauregard claim—named for the case in which such a claim was recognized, not the guy who fired on Fort Sumter). The DealerTrack patents claim a “computer aided method” of managing an automated credit application for car loans.
In both cases, neither the judges nor the lawyers seemed to have a firm sense of what standard should be applied. On the contrary, lawyers on both sides seemed to take the position that, wherever the method patent line currently is, the claims they were arguing about were either clearly short of it or well over it.
What Does It All Mean for Personalized Medicine? As Myriad illustrates, there are two kinds of gene patents that are of significance to the increasingly broad array of personalized medical research and practice: product patents on genes themselves and method patents on biomarker-based diagnostic testing and interpretation.
As we look ahead to Myriad’s resolution and beyond, it is the latter category of patents that is likely to be the more important to personalized medicine. As isolated gene patents begin to expire, or are circumvented by rapid technological advancements, the standard for the patentability of methods is unclear and seems to be getting even less clear with each new case.
Although the courts—especially the Federal Circuit—appear increasingly willing to use other patentability requirements to strike down broad claims to gene-related methods, thereby avoiding the fundamental question of which methods are patentable under section 101, this question will need to be clearly resolved at some point in order for personalized medicine to continue to thrive.