More than one-fifth of the human genome has been patented by pharmaceutical, biotechnology, and academic centers. Now, the United States (US) Supreme Court has announced it will review whether or not these patents are valid. Whichever way the court rules could have important implications for the development and licensing of diagnostic genetic biomarkers, the legal viability of clinical whole-genome sequencing, and the shape of personalized oncology in the years to come.

The US Supreme Court has agreed to review whether or not isolated human genes are eligible for patent protections under US law in early 2013. Patents allow temporary market monopolies, generally lasting 20 years, on new, nonobvious and useful inventions or processes, to reward innovator risk-taking. Patents are generally not awarded to discoveries of “laws of nature” or natural products, but since 1980, the US Patent and Trademark Office has interpreted genes isolated in the lab as patentable complex chemicals; similarly, genotype-phenotype associations are also considered patentable process inventions. Tens of thousands of genes – and by one 2005 estimate, one-fifth of the human genome – have been patented under these rules, which have helped shape the diagnostic biomarkers and biotechnology industries.

Without such market incentives, proponents warn investors will withdraw support from searches for new diagnostic biomarkers and gene therapies.  However, opponents claim human gene patents can inhibit scientific research and also reduce competition and innovation in clinical tests in ways that increase health care costs and harm patients by treating clinical data as “trade secrets,” effectively denying patients an opportunity for “second opinions” from independent diagnostic laboratories.

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The case the Supreme Court will review, Association for Molecular Pathology vs US Patent and Trademark Office, pits Salt Lake City-based Myriad Genetics and the University of Utah, which hold patents for the BRCA1 and BRCA2 genes. In addition, Myriad market’s BRCA analysis diagnostic services to test for hereditary breast and ovarian cancer risks, against the Association for Molecular Pathology, American College of Medical Genetics and Genomics (ACMG), American Civil Liberties Union (ACLU), Public Patent Foundation and other medical professional organizations and breast cancer patients.

Myriad’s patents cover BRCA1 and BRCA2 genes and mutations, and associations between mutations and breast and ovarian cancer risk. Myriad also recently secured an exclusive license for the RAD51C gene, which is associated with predisposition to breast and ovarian cancer.

A district court sided with gene patent critics in March 2010, ruling that Myriad could not patent BRCA genes because they had been discovered rather than invented. But the Federal Court of Appeals subsequently ruled that Myriad could patent “isolated” stretches of human DNA, which are not found in nature in their isolated form. Now, the Supreme Court has agreed to review the patentability of isolated human genes.

In a previous case involving Prometheus Laboratories’ patents over a diagnostic biomarker for autoimmune disease-associated thiopurine levels, the Supreme Court unanimously ruled that “natural law” correlations between biomarkers and disease cannot be patented. Despite this ruling, Myriad contends that its gene patents remain valid, because the isolated genes are a product of “human ingenuity” and are found only in the lab.

Jim Evans, MD, PhD, of the University of North Carolina, Chapel Hill, believes gene patents and exclusive licenses inhibit the development of better diagnostic tests. Diagnostic gene tests “do not have high development costs” and are “within the reach of small and university labs,” Dr. Evans has said. He points out that Lynch syndrome gene tests, for instance, are not patented or exclusively licensed, allowing many different diagnostic labs to offer diagnostic services and providing competition and choice to clinicians and hospitals. Other critics claim that Myriad’s $3,340 testing fee is beyond the reach of some patients, prevents pathologists from independently reading that portion of patients’ genomes, and even discourages research on BRCA genes, mutations, or BRCA-involved gene pathways.

Myriad vehemently denies impeding research efforts and points out that it provides the National Cancer Institute (NCI) researchers with BRCA testing “at a fraction of the commercial testing price.” Indeed, there appear to be few, if any, cases of Myriad actually halting research efforts.

Nevertheless, affirmation of isolated gene patents would present a potentially serious challenge to the implementation of next-generation clinical whole genome sequencing, worry critics. According to a November 2012 report by the Association for Molecular Pathology’s Whole Genome Analysis Working Group, published in the Journal of Molecular Diagnostics, if human gene sequences are determined to be valid, they “could present an enormous barrier to the incorporation of genome, exome and transcriptome sequencing into medical practice.”

“Genome sequencing by its nature potentially appears to involve infringement of numerous gene sequence patents, irrespective of the clinical use of the information obtained,” the authors reported. “Moreover, clinical application of the sequence information would also likely infringe on thousands of genotype-phenotype association patents. Although theoretically the data from patented genes during genome sequencing and interpretation could be blinded, this would greatly diminish the usefulness of test results.”

The authors suggested one possible solution – the creation of gene patent pools that would allow affordable access – but they acknowledged that “valuation of thousands of individual genes and genetic relationships would prove problematic” and “daunting.”

The outcome of the Myriad case “will have profound implications for the clinical application of genome sequencing,” the authors concluded.

But overturning isolated gene patents poses a threat to the biotechnology industry and should be addressed in Congress – not by the courts, Myriad has argued in court filings.

Questions for the Reader:

  • Should genes and/or their mutations be subject to patent laws?
  • Who has a stronger argument—Myriad Genetics or the opposing parties?