PROTECTING THE INTELLECTUAL FOUNDATIONS OF GENETIC SCIENCE
By Eileen Kane
Can the discoveries from genetic science be patented? There is a tension between the incentives created by the patent system-rewarding the disclosure of new knowledge with exclusive rights-and the norms of scientific research-disclosing new knowledge for further scholarly investigation. The intellectual force of reductionism in the life sciences, deepening the investigation of molecules and relationships that explain biological phenomena, generates direct conflicts with patent law's exclusion of basic knowledge from patenting. For emerging fields of science and technology, this tension surfaces immediately: the scholarly imperative to dive in and work on an unfettered intellectual landscape may clash with new possibilities for commercial development. The result is that a new scientific field may emerge that is immediately dotted with fences and boundaries-the patents that structure how its knowledge can be used.
Genetic science has not been immune to this conflict. The era of genes and genetic testing has proceeded alongside concerns that patenting efforts, in some instances, have unnecessarily reduced access for researchers, clinicians and patients to medical significant genes and methods for their use. That outcome is troubling because genetic medicine represents a paradigm shift in which disease is explained and treated according to genetically-dictated biochemical mechanisms. Genetic testing can be used to identify disease susceptibility, to establish diagnostic status, and to design personalized therapeutic regimens in medical care. Adverse patenting not only limits scientific research; it also impacts patient care. We are now approaching the resolution of two separate challenges in genetic patenting. Can genes themselves be patented? Can the scientific correlation between a gene mutation and disease susceptibility be captured as a patented method of genetic analysis?
Not everything can be patented. The Supreme Court has been quite clear that "laws of nature, natural phenomena, and abstract ideas" are not patentable, although the interpretation of this maxim has been difficult.1 Yet the underlying rationale is that scientific advances depend on an available substrate of basic knowledge, and that, therefore, patenting the intellectual foundations of a field has an adverse effect on its progress.2 The patentable subject matter doctrine in patent law, patent eligibility, performs this necessary gatekeeping function.3 The patent eligibility of genes and genetic methods can be decided by comparing these claimed inventions against the established exclusions of "laws of nature, natural phenomena, and abstract ideas" from patenting.
There is a paradoxical element to the public debate over patents pertaining to genetic science. While patent eligibility for inventions in genetic science has generated significant public controversy for years, until recently, it had yet to receive the formal legal review by the courts that could resolve the issue. Many stakeholders who were concerned about gene patenting lacked any formal standing to raise the issue in the courts. Thus, it is no surprise that the recent court cases impacting the patent eligibility of genes and genetic correlations would generate intense interest.
The Genes
In Association for Molecular Pathology v. United States Patent and Trademark Office4 a coalition of professional medical organizations, medical providers, researchers and patients challenged the eligibility of "isolated DNA" patent claims on the purified BRCA1 and BRCA2 genes, alleging that genes are both "products of nature" and "manifestations of laws of nature" for which patents may not be obtained.5 The judge accepted the arguments of the plaintiffs that the patenting of genes violates prohibitions against patenting products of nature or manifestations of the laws of nature, and ruled that the challenged patent claims were invalid.6 The argument of the defendants-that the purified gene is not a product of nature, but a product of invention-failed.
The debate continues: does purification of a gene create a new product or does it simply allow the DNA to be used for its natural function? Must a product of nature be structurally or functional identical to its natural counterpart? If purified DNA is reenacting its natural performance in the cell, then is "isolated DNA" really any different than the natural form? Moreover, is the function of DNA particularly special? All of these overtones are apparent in the AMP case, and the eligibility of DNA can be analyzed utilizing patent law standards, without recourse to non-legal genetic exceptionalism. The purified gene is often claimed as an isolated complementary DNA, or cDNA, the abbreviated, message-bearing form of the gene, a result of laboratory manipulation, reflecting divergence from the physical genomic form.7 However, all of that structural investment is done to preserve the natural informational content of the gene: the maintenance of its functional identity. Thus, we must ask what the product of nature doctrine is trying to accomplish by prohibiting the patenting of natural products. The underlying goal appears to be preserving access to natural products and knowledge where no truly inventive alteration has taken place. It is obvious that the purified gene is valuable precisely because it reprises its natural behavior outside the cell. The purified gene is surely the clone of its cellular self, and a product of nature that cannot be patented.
However, there is more complexity. DNA is not like other biomolecules. It is important to understand the complex set of attributes that distinguish DNA from other molecules-its identity as both chemical and template-and how these attributes impact the patenting analysis. The discovery of the structure of DNA ended the most impassioned search in the history of biological science: to identify where genetic information was encapsulated and how it was transmitted. The gene emerged as the molecular repository of an embedded code-the genetic code, a long-sought law of nature.8 This code was deciphered in order to establish how DNA instructs the execution of proteins.9 The Human Genome Project began to assemble the set of specific embodiments-the genes-that account for human form and function.10 Genes are nature's exemplars of the genetic code; as such, they embody this law of nature.11 It has long been established that "manifestations of laws of nature [are] free to all men and reserved exclusively to none."12 Following from the Supreme Court's dictate that the laws of nature are not patentable, it can be concluded that the patenting of genes effectively preempts the genetic code, and is therefore not allowable.13 This becomes a separate analytic basis for concluding that genes are ineligible for patenting.
The Genetic Correlations
The patenting controversies in genetic science continue. Can one patent the observation that a mutation in a gene, such as BRCA1, is associated with a higher susceptibility to early-onset breast and ovarian cancer? Can this scientific correlation be captured in a patented method without running into the exclusion of "laws of nature, natural phenomena, and abstract ideas" from patenting? Maybe not. The AMP litigation also presented this issue, asking whether patenting the method of utilizing the relationship between a mutation in the BRCA1 gene and a higher cancer risk was, in effect, the patenting of a natural phenomenon. Again, the judge sided with the plaintiffs, although the reasoning employed a legal test that has now been discarded by the Supreme Court in the business method patent case, Bilski v. Kappos.14 Other recent cases in the life sciences focus on whether scientific correlations can form the basis for a patented method: LabCorp v. Metabolite15 (a diagnostic method for detecting a vitamin deficiency using the quantitative correlation between the level of the amino acid homocysteine and several B vitamins), Prometheus v. Mayo16 (a treatment method using the correlation between a metabolite level and drug toxicity to more precisely tailor pharmaceutical dosage), and Classen v. Biogen17 (a method for optimizing an immunization regimen utilizing the correlation between administration and effect). Prometheus, Classen and AMP will now be recalibrated in the post-Bilski framework; the Federal Circuit will have an opportunity to revisit the eligibility of scientific correlations as patent method claims using the law of nature/natural phenomena analysis. As a result of the fact that these important patent cases involving method claims have been litigated without directly reaching the public domain questions embedded in the patentable subject matter doctrine, the field awaits more definitive guidelines for how the detailed investigation of biological mechanism can coexist with patent law's prohibition on patenting basic and essential knowledge.
The significance of determining whether scientific correlations are subject to patenting cannot be overstated. Beyond the identification of the molecules that perform biochemical tasks, modern biological research focuses on determining dynamic intermolecular relationships and biochemical causation. The contested method claims in biochemical or genetic testing are heterogeneous, where a patent claim may cover, for example, quantitative relationships between molecules, the mechanism of pharmaceutical metabolism, or the cause and effect relationship between genotype and phenotype. While the universe of biological molecules may be finite, the set of relationships and interactions that define human metabolism are likely to be vast. Therefore, it is essential to establish whether every observation of molecular performance can be converted into a patent claim. It is fair to conclude that the animating rationale for excluding natural phenomena from patenting would apply to exclude these types of patent claims. For genetic science, this would translate as a prohibition against patenting the fundamental genotype/phenotype correlations that underlie genetic medicine.
The article concludes that genes and genotype/phenotype correlations form the intellectual foundations of the genomic era in science, and are the kind of basic knowledge tools that fall within the exclusions from patentable subject matter. In the near future, AMP will present the Federal Circuit, and possibly the Supreme Court, with the opportunity to settle these critical eligibility questions for patent law. Resolution of the eligibility controversies in genetic patenting is important for genetic medicine and also has larger theoretical implications. The life sciences await a definitive and modern interpretation of the product of nature doctrine and its scope, and a contemporaneous analysis of whether and how correlations in the life sciences are regarded as natural phenomena or laws of nature. Other scientific sectors are also impacted by any judicial reaffirmation that basic knowledge cannot be patented, such as nanotechnology and other fields in the physical sciences.
The patenting of applied research and true invention can coexist alongside the preserve of open and available knowledge. More narrowly tailored patent claims in genetic science can be imagined, including therapeutic applications of genes engineered into specific molecular constructs and the use of scientific correlations embedded within specific genetic testing protocols. Such inventive precision will allow creative applications of fundamental knowledge to emerge and legitimately solicit legal protection, while the intellectual substrates for genetic science remain unowned. That is an optimal balance.
Eileen M. Kane, PhD, JD, is Professor of Law at Penn State Dickinson School of Law.
1. Diamond v. Diehr, 450 U. S. 175, 185 (1981).
2. The Supreme Court has stated: "Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work." Gottschalk v. Benson, 409 U.S. 63, 67 (1972).
3. 35 U.S.C. § 101. The statute authorizes the patenting of "any new and useful process, machine, manufacture, or composition of matter." Id.
4. Association for Molecular Pathology v. U.S. Patent & Trademark Office, 702 F. Supp.2d 181 (S.D.N.Y. 2010).
5. Id. at 227.
8. Eileen M. Kane, "Splitting the Gene: DNA Patents and the Genetic Code," 71 TENNESSEE LAW REVIEW 707, 752 (2004).
9. Lily E. Kay, WHO WROTE THE BOOK OF LIFE?: A HISTORY OF THE GENETIC CODE (2000).
10. International Human Genome Sequencing Consortium, "Finishing the Euchromatic Sequence of the Human Genome," 431 NATURE 931 (2004).
11. Kane, supra note 8, at 753.
12. Funk Bros. Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 130 (1948).
14. Bilski v. Kappos, 130 S.Ct. 3218 (2010). The Supreme Court has now rejected the machine or transformation test as the exclusive test for patent eligibility, which was used by the judge to decide the method claims in AMP.
15. Lab. Corp. of Am. Holdings v. Metabolite Labs., Inc., 548 U.S. 124 (2006).
16. Prometheus Labs. v. Mayo Collaborative Servs., 581 F.3d 1336 (Fed. Cir. 2009), vacated and remanded, 2010 WL 2571881 (U.S. June 29, 2010).
17. Classen Immunotherapies v. Biogen IDEC, 304 Fed. Appx. 866 (Fed. Cir. 2008), vacated and remanded, WL 2571877 (U.S. June 29, 2010).