NEJM -- Gene Patenting -- Is the Pendulum Swinging Back?

Gene Patenting — Is the Pendulum Swinging Back?
Aaron S. Kesselheim, M.D., J.D., and Michelle M. Mello, J.D., Ph.D.

Are human genes and the process of comparing DNA sequences patentable? These questions were raised by a group of researchers, pathologists, patients with cancer, and medical professional organizations challenging some of Myriad Genetics' patents covering the BRCA1 and BRCA2 genes and their use in screening for elevated risks of breast and ovarian cancer. On March 29, in a startling decision, a federal district court judge invalidated many of Myriad's patent claims,1 reigniting a long-simmering debate about the patentability of genes.

The Patent Act permits exclusive control for a limited time (currently 20 years) of any "process, machine, manufacture, or composition of matter," and since its inception, the U.S. Patent and Trademark Office (USPTO) has granted patents on new pharmaceuticals and medical devices. However, as recently as the 1970s, the view among many medical researchers and legal scholars, as well as members of the USPTO, was that DNA sequences were not patentable, primarily because DNA is a naturally occurring substance rather than a human invention. This perception changed in 1980 with the Supreme Court's landmark ruling in Diamond v. Chakrabarty,2 which involved a dispute over the patentability of a microbe that dissolves oil and that had been specially constructed to include a DNA plasmid. The Court held that although the Patent Act did not authorize ownership of laws of nature, "products of nature," or physical phenomena, "anything under the sun made by man" was patentable, including the human-made bacterium at issue in the case.

After the decision, gene patents — specifically, patents on "isolated DNA" — soon became commonplace. USPTO examiners justified this extension of patent protection on the grounds that the patented genes and DNA sequences had been purified (and therefore transformed) from their natural form through the application of artificial tools. By the 1990s, technological advances in DNA-sequencing strategies began enabling scientists to discover and isolate new genes at a rapid rate. Ultimately, thousands of patents were awarded on different parts of the human genome sequence; reportedly, about 20% of human gene DNA sequences are currently patented.

Myriad was founded in 1991 by Walter Gilbert, who won a Nobel Prize for his work in nucleic acid sequencing, and Mark Skolnick, a geneticist who had spent his career working on the familial characteristics of cancer. In 1994, building on publicly funded research on the hereditary predisposition to breast cancer that had been conducted in several countries throughout the 1980s and using about $22 million in private venture capital, Myriad's team won a race with several other groups to identify the nucleotide sequences composing the BRCA1 gene (see timeline). Myriad's team included collaborators from the University of Utah, the National Institute of Environmental Health Sciences, McGill University, and Eli Lilly and was also supported by grants from the National Institutes of Health and the National Cancer Institute of Canada. A year later, Myriad filed for a patent on the BRCA2 gene, although it may not have been the first to identify its sequence. Myriad's patents, the earliest of which expire in 2014 and 2015, cover isolated gene sequences, as well as methods of "analyzing" and "comparing" the gene sequences to determine whether the mutations conferring an increased risk of breast or ovarian cancer are present. Myriad launched its combined genetic test, BRACAnalysis, in November 1996. In 2009, the test accounted for most of the company's $326 million in annual revenue from molecular diagnos

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NEJM -- Gene Patenting -- Is the Pendulum Swinging Back?