May a gene be patented? Or does a gene belong to all of humanity? It has long been held in the United States that inventions reflecting the “hand of man” can be patented. It has also long been established there that products of nature, abstract principles or natural phenomena may not be patented, but the applications of abstract principles or natural phenomena may. Since the early 1980s the United States Patent and Trademark Office (PTO) has issued patents on isolated DNA sequences, but the issue of whether such patents were patentable subject matter had never been challenged in court.

In May 2009 that changed when various individuals, medical researchers and organisations represented by the American Civil Liberties Union (ACLU) filed suit in New York challenging gene patents held by Myriad Genetics (Myriad). The patents cover two genes—BRCA1 and BRCA2— and methods for correlating mutations in those gene sequences. Mutations in the genes are detected through a Myriaddeveloped diagnostic test used to determine whether a woman is predisposed to breast and ovarian cancers. The cost of the test is approximately US$3,000 and, according to plaintiffs, Myriad is its sole supplier. Further, according to plaintiffs, Myriad has threatened to sue any entity that provides the diagnostic test or entities that perform research on BRCA1 and 2 mutations.

The ACLU suit sought ef fectively to overturn a long-standing policy of the PTO that isolated gene sequences are patentable subject matter. Under this policy the PTO has issued thousands of patent claims directed to isolated DNA sequences. Plaintiffs stylised the suit as one of control over one’s personal genome, which is the very definition of a natural product that the patent laws do not cover. Plaintiffs further argued that patenting basic genetic sequence information impedes medical progress.

Myriad, with support from the life sciences industry, argued that patented gene sequences isolated from an individual through a series of chemical manipulations were no longer a product of nature and did not preempt all uses of the sequence. Myriad and other life science companies further argued that a broad ruling striking down these types of patent claims would have a deleterious effect on the US biotechnology industry, retarding the development of new diagnostics and therapeutics tailored to an individual’s genomic make-up. The US Congress on several occasions in the past has considered, but not passed, legislation addressing whether there should be restrictions on the ability to patent genes.

On 29 March 2010 Judge Sweet of the US District Court for the Southern District of New York answered the question by granting the plaintiffs’ motion for summary judgment in Association for Molecular Patholog y et al v USPTO and Myriad et al 09-CV-4515. The highly significant ruling found that Myriad’s patent claims directed to isolated DNA sequences, methods of detecting BRCA mutations and methods of using cells transformed with BRCA to screen for potential drugs are unpatentable subject matter under 35 U.S.C. Section 101.

Specifically, for the claims directed to just isolated DNA encoding the BRCA1 or 2 proteins (or fragments thereof), Judge Sweet held these claims were unpatentable subject matter because they claimed a product of nature. In doing so, Judge Sweet held that products isolated from nature must possess “markedly different characteristics” from the product in nature to constitute patentable subject matter. Notably, the Court rejected the application of the isolated DNA in gene therapy or for use in recombinant protein expression as evidence of a marked dif ference. In rejecting this evidence, the Court focused on the similar properties of the claimed isolated DNA and DNA in nature (i.e., the genetic information encoded in its sequence). Further, Judge Sweet said DNA is “distinct in its essential characteristics from any other chemical found in nature [and its] existence in an ‘isolated’ form alters neither this fundamental quality of DNA as it exists in the body nor the information it encodes”.

Myriad’s method patents claimed methods of detecting BRCA mutations in a patient. Judge Sweet held these claims invalid because the claimed methods constituted unpatentable abstract mental processes of comparing or analysing two gene sequences, and the claimed steps of analysing and comparing failed to recite the specific transformative steps that are a hallmark of patentable subject matter. Judge Sweet further noted that even if the analysing or comparing steps were interpreted to include the steps of isolating DNA from a patient and sequencing that DNA, these transformative steps would be nothing more than data gathering, which is insufficient to meet the transformation requirement.

Myriad’s cell-screening patent claimed methods of identifying compounds useful in treating BRCA-associated cancer by screening compounds against cells transformed with BRCA. Again Judge Sweet held these method claims failed the t ransformat ion test because the transformative steps were mere data gathering. In a footnote, Judge Sweet rejected the argument that drugs that affect the BRCA cell impart a patentable transformation for the claim because compounds that fail in the screen would have no such transformative effect.

Myriad has appealed this broad ruling and the appeal is now pending before the US Court of Appeals for the Federal Circuit. Briefing by the parties is ongoing and, on 29 October 2010, several friends of the court, or “amicus”, briefs were filed. Surprisingly, the US Department of Justice (DOJ) filed an amicus brief opposing the patenting of genes per se, acknowledging that its position was at odds with the PTO policy, as well as various governmental agencies obtaining patents on such isolated DNA sequences. However, the brief acknowledged that chemical manipulations that result in, for example, cDNA, or genetically engineered crops or microorganisms, would constitute patentable subject matter, as these patent claims reflect more than the mere isolation and purification of a product from nature.

In cont rast, a separate coal it ion of personalised medicine companies and organisations argued that Myriad’s method claims comparing alterations in gene sequences from patient tissue samples for screening should be upheld under US Supreme Court precedent. The amicus brief further argued that a broad view of patentable subject matter was necessary to maintain the incentives to invest in personalised medicine. Without a broad view of patentable subject matter, the amici argued, “diagnostic companies would struggle to attract the investment necessary to drive future research and development”, thereby “negatively impacting the US economy and diminishing the rate of advance toward new treatments powered by molecular information”.

Judge Sweet attempted to limit the reach of the case by holding that DNA is a unique chemical molecule. Ultimately, however, many life science inventions intersect with nature. Powerful natural agents, such as taxol, have been isolated from nature and used as new chemotherapeutic agents. Proteins and antibodies based on natural products are used as therapeutic agents. In short, the life sciences draw on nature and where the courts ultimately draw the line may have broader ramifications.

The Federal Circuit Court will likely issue its decision by the middle of 2011. Any predictions on how the Court will rule are speculative, with a number of possible options. Ultimately, however, it is likely the US Supreme Court will answer definitively the question of whether isolated DNA sequences and methods for correlating sequence mutations may be patented.