Posted: September 30th, 2011
By Mark Vaders *
Should unaltered genes be patentable as compositions of matter? Chief Justice Warren Burger, in Diamond v. Chakrabarty, wrote that Congress “[R]ecognized that the relevant distinction [between patentable and non-patentable] was not between living and inanimate things, but between products of nature whether living or not, and human-made inventions.” Patentable subject matter is restricted to “product[s] of human ingenuity ‘having a distinctive name, character [and] use.’” This language made clear that “products of nature” do not constitute “manufactures” or “compositions of matter” as meant within 35 U.S.C. § 101, and thus no party “may obtain a patent therefor.” The question remains, however–are isolated genes products of nature or of human ingenuity?
Judge Robert Sweet, in his recently overturned district court opinion, electrified the gene patent debate by declaring invalid 15 patent claims relating to the BRCA1 and BRCA2 genes held by Myriad Genetics. Mutations in these “tumor suppressor” genes are associated with greatly increased risk of breast/ovarian cancer (see here). Judge Sweet held that “DNA represents the physical embodiment of biological information, distinct in its essential characteristics from any other chemical found in nature. It is concluded that DNA’s existence in an ‘isolated’ form alters neither this fundamental quality of DNA as it exists in the body nor the information it encodes.” While not a biologist himself, Judge Sweet did his homework and examined this issue from a biologist’s perspective. The importance of DNA is that its sequence determines the protein(s) it can code for or what signaling/regulatory molecules can bind there. When diagnostic labs isolate genetic material and determine its sequence, they are using that isolated DNA as a surrogate for the identical sequences located within the patient’s cells. That sequence is not a product of human ingenuity–if it was, the molecule would no longer be useful in the manner that makes it valuable.
Unfortunately, the history of gene patenting has not been governed by a biological perspective. Group art units at the USPTO specializing in the biological sciences are a more recent phenomenon, so the backdrop for this debate has been established by chemists. As pointed out by Judge Moore in the Federal Circuit opinion reinstating the validity of isolated gene patents, there is a long history of the USPTO granting patents on isolated molecules and compounds. Judge Laurie, writing the majority opinion, spent a considerable effort analyzing chemical diagrams of DNA and explaining how isolated DNA is different from purified DNA. Isolated DNA, Judge Laurie concluded, is a distinct chemical entity from DNA found within the human body.
While it is undeniable that an isolated DNA sequence is chemically distinct from intact DNA, relying on that fact to justify the patenting of such sequences seems horribly out of sync with the real-life application of the material. Though it is possible Judges Laurie and Moore may be more chemistry-minded, the primary underlying reason for their reinstatement of the gene patents seems to be concern over upsetting the settled expectations of the biotechnology industry. The oft-cited figure that 20% of the human genome has been patented (see Christopher Holman’s paper debunking that number) suggests that hordes of venture capitalists would be quite put out to find their intellectual property vaporized. How much money can be made off of a successful gene patent? Look no further than Myriad Genetics to find out.
Myriad, founded in 1991 by Dr. Mark Skolnick and a Utah-based venture capital group, has become the poster-villain of gene patenting due to the high price it charges for its BRAC1/2 tests and its refusal to grant licenses to other service providers. The company received a total of $22 million in funding between 1991 and 1994. In 1994 and 1995, respectively, Myriad filed for patents on the isolated BRCA1 and BRCA2 genes. According to Myriad’s Annual Reports filed with the SEC (available here), the company began seeing revenue for “genetic testing” beginning in 1997, and by 2001, had pulled in a grand total of almost $40 million. For the fiscal year ending in 2010, Myriad pulled in $362.6 million, touting that their BRACAnalysis test accounted for the majority of the revenue.
Opponents of gene patents such as the ACLU and PUBPAT point to Myriad as an example, claiming that basic research is being actively prevented and patients are being denied access to their own genes. Proponents argue that gene patents are necessary as an incentive for investors to devote funding for commercialization. The truth of the matter is unclear according to Dr. Robert Cook-Deegan, director of the Center for Genome Ethics, Law and Policy at Duke University. Is research truly being stymied? A quick search on PUBMED for “BRCA1 BRCA2” in humans reveals that nearly 4,000 papers have been published since Myriad’s patenting of those genes in 1994/1995. Basic research seems to be going strong, and Dr. Cook-Deegan points out that many companies love university research on their patented genes because such research makes them more valuable–and the universities are rarely engaging in activity where damages could be easily calculated in an infringement suit. The loser here is the development that follows basic research. New discoveries unanticipated by patent holders are potentially being commercially delayed because an isolated gene patent prevents anyone other than the patent holder from isolating the claimed sequence for 20 years–which in biotechnology is an eternity.
While as a matter of law and biology I believe gene patents should be invalidated, it seems there are aspects of this debate that are being overlooked. Jeffrey Brown points out in his PBS article that the “major goal” of modern research has been to link genes with the diseases they cause. I believe this really is the crux of the issue. The sequence of a gene is no longer valuable in and of itself except for excluding access by others–the Human Genome Project has made access to sequence data commonplace. The valuable information is which genes are associated with a particular malady and why. Thanks to second-generation technologies, sequencing today is cheap–costing as little as $0.19 per each MILLION base pairs. Increasingly sensitive microarrays have made genotyping similarly affordable, with offerings such as Illumina’s 1M Duo allowing 1.2 million loci to be tested at once. Service providers such as 23andMe allow customers to obtain their own Illumina-derived genotyping data for approximately 1 million SNPs at a cost of only $99.00. If genetic sequence patents threaten to quagmire whole genome sequencing efforts, expect the already tenuous public tolerance of gene patents to disintegrate rapidly.
Given the proliferation of such data in the public domain, surely the clock is ticking for the USPTO to begin denying isolated sequence claims due to obviousness under 35 U.S.C. § 103? I would not fear for the biotechnology industry, however, even in the absence of isolated gene patents. After all, Myriad was crystal clear in its 2010 Annual Report to its shareholders–even without the 15 claims invalidated by Judge Sweet, the company still possesses “164 separate claims under [the relevant] seven patents” which protect aspects of the intellectual property used in BRACAnalysis, as well as 16 additional patents not called into question. Their final word? “[W]e do not believe that this lawsuit will have a material adverse impact on the Company.”
* Mark Vaders is a second-year J.D. candidate at Wake Forest University. He is Secretary of both the Wake Intellectual Property Student Association and the Executive Board of the Honor Council, and will be a Fall 2011 intern for the Wake Forest University Office of Technology Asset Management. Mr. Vaders holds a Masters in Genetics from N.C. State University and was formerly employed as a Clinical Study Manager at Beckman Coulter Genomics. He intends to practice Intellectual Property Law in the state of North Carolina upon graduation in May 2013.