By Andrew W. Torrance
July 6, 2009 | The American Civil Liberties Union (ACLU) would seem an unlikely candidate to be interested in genetic tests for diagnostic mutations. From its origins in the struggle to prevent the United States from entering World War I, the ACLU has evolved into a self-proclaimed “guardian of liberty,” traditionally focusing on provisions of the Constitution protecting freedom of speech, equal protection, and privacy. However, last month (on May 12, 2009), on behalf of several medical associations, advocacy organizations, physicians, researchers, and individuals, the ACLU filed a lawsuit naming the United States Patent and Trademark Office (USPTO) and Myriad Genetics among the defendants in a potentially historic patent case.
The ACLU’s lawsuit ostensibly focuses on the legitimacy of the infamous BRCA1 and BRCA2 breast cancer gene patents granted to Myriad Genetics, but it seeks nothing less than the elimination of human genes as patentable subject matter. In the words of its complaint: “Every person’s body contains human genes, passed down to each individual from his or her parents. These genes determine, in part, the structure and function of every human body. This case challenges the legality and constitutionality of granting patents over this most basic element of every person’s individuality.”
The lawsuit calls out the dangers of more than just human gene patents. It also condemns the patentability of “the concept of looking at or comparing human genes, and correlations found in nature between certain genes and an increased risk of breast and/or ovarian cancer”.
Roughly 13% of American women (1 in 8) will develop breast cancer at some point during their lives—almost 200,000 new cases and more than 40,000 deaths per year. Women who carry inherited mutations in their BRCA1 or BRCA2 genes face increased risk of 36-85%, as well as heightened risk of ovarian cancer (16-60%). The BRCA1 gene was isolated and subsequently patented (along with BRCA2), and is now owned by Myriad, a Salt Lake City biotech company, which also maintains a patent monopoly on the diagnostic sequencing tests—tests that cost around $3000 and are out of reach to many lacking healthcare insurance.
Any Gene Under The Sun
But the ACLU patent case goes to the very heart of gene patents. Genes have long been patentable, and myriad genes (including Myriad’s genes) are currently claimed in patents in the United States and elsewhere. Since 1975, the USPTO has issued more than 15,000 patents whose claims contain the word “gene.” In 1972, Ananda Chakrabarty, a biologist at General Electric Company, filed a U.S. patent application for a genetically engineered strain of Pseudomonas bacteria. The U.S. Supreme Court, in a watershed 1980 decision (Diamond v. Chakrabarty), allowed the patent (4,259,444) to issue, and famously declared that “anything under the sun that is made by man” might qualify for patent protection. The USPTO waited until 1982 to issue its first patent claiming genes per se. The number of patents issued with claims mentioning “genes” or “DNA” peaked in 2001, declining since then.
Section 154 of The Patent Act confers on a patent owner “the right to exclude others from making, using, offering for sale, or selling the invention throughout the United States.” This right to exclude others is especially controversial in the realm of gene patents. Kyle Jensen and Fiona Murray estimated that, by 2005, almost 20% of human genes had been claimed in a U.S. patent. Michael Heller and Rebecca Eisenberg worried that excess patenting of human genes could lead to a tragedy of the “anticommons” capable of chilling further genetic research. As the late Michael Crichton wrote in an outraged Op-Ed in the New York Times in 2007:
“YOU, or someone you love, may die because of a gene patent… Gene patents are now used to halt research, prevent medical testing and keep vital information from you and your doctor.”
But the situation may not be as dire as opponents of gene patents suggest. In a study on litigations involving patents in his comprehensive database of human genes claimed in patents, Christopher Holman found that, “not one of the 4,270 patents in the dataset has ever been found to have been infringed or been the basis of a preliminary injunction.”
The biotech industry argues, with some justification, that substantial investments in search of novel diagnostics and drugs would not be possible without patent protection for genes and their uses. As Sheila Jasanoff writes in her book, Designs on Nature, “extension of patents to the life sciences created new classes of property rights in things that were previously outside the realm of what could be owned, or even thought of as subject to ownership claims. As a result, these objects became commodities that could have value, be exchanged, circulate in markets, and foster productivity.”
Nevertheless, in the absence of profitability for the biotech industry as a whole, it has been suggested that biotechnology has so far been more successful at producing patents than drugs. Availability of patent protection for genes has generally been assumed to spur the discovery and elucidation of more new genes, while simultaneously limiting others’ access to those same new genes. In fact, Michael Meurer and James Besson, in their book Patent Failure, confirm the economic value of biopharmaceutical patents, even though they cast doubt on the value of patents in other industries.
One Appeal, Two Issues
In its lawsuit, the ACLU has decided to tackle two of the most controversial issues in patent law -- human genes and diagnostic methods. It has gathered a group of extremely sympathetic plaintiffs, including patients seeking access to medical diagnosis of a devastating disease and medical professionals requesting the right to deliver such diagnosis without fear of infringing a corporation’s patents. (One plaintiff was unable to get a second opinion on her breast cancer test; another could not get coverage of the test through Medicaid.) If successful, the ACLU could substantially redraw the patentability landscape that undergirds the biotech industry, and possibly alter the balance of incentives to promote new genetic discoveries and the development of new therapies and diagnostics.
Two hurdles stand in the way of the ACLU and its plaintiffs. First, genes have long been considered patentable subject matter. Despite arguments portraying genes as discoveries or the common patrimony of humanity, it is unlikely that any Federal court will overturn the 29 years of precedent beginning with Diamond v. Chakrabarty. To do so would invite vigorous opposition by the biotech industry and swift reversal by the Federal Circuit or the Supreme Court.
Second, none of the plaintiffs who sued Myriad have themselves been sued for infringing Myriad’s patents. This could trigger a constitutional doctrine called “standing” that restricts who is allowed to bring a lawsuit. The USPTO is likely to be granted substantial deference in its interpretation of the Constitution, the Patent Act, and related judicial decisions; its interpretation that genes constitute patentable subject matter will be difficult to overturn unless Congress does, indeed, amend the Patent Act to ban gene patents.
On the issue of diagnostic patents, however, the ACLU may be on firmer ground. In light of recent decisions (see Sidebar “Patently Controversial” below), methods of diagnosis that rely on correlation, or other relatively simple reasoning, appear vulnerable to challenges that they do not constitute patentable subject matter. A Supreme Court decision in In re Bilski could certainly be decisive, either for or against patentability of diagnostic methods. A year from now, the prospects for diagnostic methods such as Myriad’s BRCA tests will likely be much clearer.
By forcing the issue into court, the ACLU has raised what were once esoteric issues of patentable subject matter to new heights of public awareness. Such prominence is unlikely to endear existing patent law doctrine to those who rely upon, pay for, and fear being excluded from medical care. Even if the ACLU fails in court, its gambit will likely harm the future prospects of human gene patents and diagnostic patents by emphasizing the image of patent monopolists who assert ownership over natural molecules and then restrict access to medical care.
Although the issues surrounding patentable subject matter in biotechnology are much more complex and important than this negative image conveys, the next time Congress rushes to limit such patents, it will likely find a much larger constituency supporting its efforts.
Andrew W. Torrance is an associate professor at the University of Kansas School of Law. He can be reached at Email: firstname.lastname@example.org
Patent law has already responded to limit human gene patents. For example, in 2005, the Court of Appeals for the Federal Circuit decided a case called In re Fisher that involved claimed “expressed sequence tags” (ESTs) -- gene fragments rather than whole genes. Monsanto cited the usefulness of ESTs in locating whole genes in the maize genome, but the Federal Circuit rejected the claim to ESTs on the grounds that it lacked enablement and utility.
While In re Fisher made it more difficult to patent gene-based inventions, the influential Supreme Court decision, KSR International v. Teleflex, by tightening the nonobviousness requirement, has made it more challenging to patent inventions in all areas of technology. Furthermore, a renewed judicial interest in patents that implicate human thought may signal difficulties for patents claiming gene diagnostic tests.
Congress has also noted the anxiety over gene patenting, even considering amendments to the Patent Act that would effectively ban gene patents. In 2007, Congressman Xavier Becerra (D-CA) proposed the “Genomic Research and Accessibility Act.” This bill would have provided that “no patent may be obtained for a nucleotide sequence, or its functions or correlations, or the naturally occurring products it specifies.”
To date, genes remain patentable subject matter and gene patents remain potentially valid and enforceable. However, the future is now less certain in the face of increased judicial and Congressional scrutiny. In addition, empirical evidence suggests that issued gene patents are rarely asserted against others in litigation. The ACLU may have chosen a propitious moment to challenged Myriad’s patents.
The ACLU’s lawsuit against the USPTO and Myriad Genetics is something of a sequel. The organization previously filed an amicus brief in a high-profile Federal Circuit appeal called In re Bilski. This case considered an invention alleged to require a “mental step” capable of being carried out by a human mind. In the middle of the 20th Century, courts developed a judicial doctrine – “mental steps doctrine” – to limit patents whose claims implicated human thought. In 1951, the Court of Customs and Patent Appeals stated in its In re Abrams decision, “[i]t is self-evident that thought is not patentable.”
In 2006, Supreme Court reversed its decision to decide an appeal on the patentability of method of medical diagnosis. The patent claim in Laboratory Corp. v. Metabolite Laboratories, was a method for detecting a deficiency of cobalamin or folate in warm-blooded animals based on “assaying a body fluid for an elevated level of total homocysteine; and correlating an elevated level of total homocysteine in said body fluid with a deficiency of cobalamin or folate.”
The litigants agreed that “assaying a body fluid” referred to any test that detects an elevated level of total homocysteine. Furthermore, the inventors testified that “correlating” simply referred to a doctor recognizing an elevated level of homocysteine, a result that “would occur automatically in the mind of any competent physician.” After the Federal Circuit found that claim 13 was not invalid, and that Laboratory Corp. had infringed it, the Supreme Court granted Laboratory Corp.’s petition for certiorari. The court limited the appeal to a single question:
“[w]hether a method patent . . . directing a party simply to ‘correlate’ test results can validly claim a monopoly over a basic scientific relationship . . . such that any doctor necessarily infringes the patent merely by thinking about the relationship after looking at a test result.”
Despite widespread anticipation of a decision definitively affirming or restricting “human thought” patents, the court declined to decide the case on the grounds that the writ of certiorari had been improvidently granted. This left the decision of the Federal Circuit intact. Justice Breyer wrote a blistering dissent, in which he argued that claim 13, and claims like it, should be unpatentable.
In the wake of the Supreme Court’s non-decision, the lower courts decided a flood of cases involving patent claims alleged to involve thinking steps. Among these were the In re Comiskey and In re Bilski cases, both recently decided by the Federal Circuit. The latter invention involved “a method practiced by a commodity provider for managing (i.e., hedging) the consumption risks associated with a commodity sold at a fixed price.” The Federal Circuit stated the legal issue they would decide as follows:
Whether the claimed subject matter is not patent-eligible because it constitutes an abstract idea or mental process; when does a claim that contains both mental and physical steps create patent-eligible subject matter?
To decide the case, the court articulated a “machine-or-transformation” test, declaring that “[a] claimed process is surely patent-eligible … if (1) it is tied to a particular machine or apparatus, or (2) it transforms a particular article into a different state or thing.” Neither applied in this case, and so the court held the claims to be unpatentable.
In re Bilski has important implications for medical diagnostic patents. Citing the In re Bilski decision in December 2008, the Federal Circuit, in Classen v. Biogen, affirmed a lower court’s decision to invalidate patent claims on “evaluating and improving the safety of immunization schedules”. The lower court found that “the correlation between vaccination schedules and the incidence of immune mediated disorders that Dr. Classen claims to have discovered is a natural phenomenon.”
In another case decided last April, Ariad Pharmaceuticals v. Eli Lilly, the Federal Circuit found patent claims relating to modulating gene expression invalid for lack of adequate disclosure, and shed little light on patentable subject matter. Interestingly, Myriad Genetics considers the Prometheus v. Mayo appeal (which deals with patent claims covering methods of optimizing treatment of Crohn’s disease) vital enough to its own interests that it has filed an amicus curiae brief urging the Federal Circuit to reverse the lower court’s decision.
Allowing the patenting of “human thought” per se would clearly be problematic. As Dan Burk points out, “there would seem to be profound First Amendment implications to the concept of infringement by ‘thinking patented thoughts’.” The Supreme Court has just granted certiorari for In re Bilski, to clarify the patentability of inventions involving human thought, and to provide the sort of guidance it declined to provide in Laboratory Corp. Providing the Supreme Court actually renders a decision this time, the patentability landscape for biotechnological inventions may be altered significantly.