May 1, 2007 (Vol. 27, No. 9)

As Testing Becomes Mainstream, Challenges Have Begun to Arise from Patent Holders

As the use of genetic testing has become more frequent, holders of patents on genes, genetic variants, and their biological correlations are using the threat of litigation to force laboratories to stop performing genetic tests. Some laboratories have already discontinued genetic testing for muscular dystrophy and other severe neurodegenerative illnesses. However, legal precedent on patent protection suggests that their threats may lack substance.

The 1970s and early 1980s in the United States were plagued by high unemployment, high inflation, and a decline in economic confidence. In response, Congress took a number of steps to encourage the growth of domestic technology industries. Among the most significant of these were changes to the U.S. patent system. Because we did not appear to be deriving maximum economic value from our substantial federal investments in basic science research, Congress in 1980 enacted the Bayh-Dole Act.

Bayh-Dole encouraged universities to patent, and thereby commercialize, inventions arising out of government-sponsored research grants. Accompanying the enactment of Bayh-Dole, and in the years subsequent to its passage, federal financial commitments dedicated to biomedical research dramatically increased. As a consequence of these governmental actions, the number of patents assigned to universities increased from 264 in 1979 to 3,259 in 2003.

Other important events took place on the legal front. In the landmark 1980 case of Diamond v. Chakrabarty, the U.S. Supreme Court made it clear that man-made, living organisms could be patented. Chakrabarty, a research scientist, applied for a patent on a Pseudomonas bacterium that was bioengineered to carry multiple plasmids.

The Patent Office (PTO) rejected Chakrabarty’s patent application on the grounds that living organisms were not patentable. Chakrabarty appealed the PTO’s decision, and the case ultimately made its way to the United States Supreme Court. Urging a broad interpretation of patent eligibility, the Supreme Court recited a now famous quote, stating that “anything under the sun that is made by man,” including living organisms, could be patented.

In order to provide national uniformity and add greater certainty and expertise to the application of patent law, Congress in 1982 created a national appeals court with exclusive jurisdiction for patent cases. This court is referred to as the Court of Appeals for the Federal Circuit. Since the Court’s inception, Federal Circuit decisions have largely been viewed as expanding patent-eligible subject matter and strengthening the rights of patent holders relative to potential infringers. On no scientific field has the impact of this Court’s decisions been more acutely felt than biotechnology. Thousands of patents have been issued on biotechnology inventions from transgenic mice and leukemia-derived cell lines to recombinant drugs and vaccines.

The coalescence of these events set the stage for enormous growth in the United States biotechnology industry. FDA approvals for biotechnologically produced drugs and vaccines grew from 2 in 1982 to 35 in 2002. The number of U.S. biotechnology companies expanded from 225 in 1977 to 1,457 in 2001.

The PTO and the Court of Appeals for the Federal Circuit have largely followed the Supreme Court’s mandate to interpret patent eligibility broadly. Despite its dual roles as a physical substance and a store of biological information, our legal system has treated DNA as a chemical. In the frequently cited Federal Circuit case of Amgen v. Chugai, the Court wrote, “A gene is a chemical compound, albeit a complex one.”

Prior precedents in chemical law have been applied to isolated DNA sequences, including those that permitted the patenting of purified chemical compounds like aspirin, Vitamin B12, and prostaglandins. The chemical analogy has allowed patents on isolated, purified human genes to circumvent the “product or nature” doctrine, a longstanding rule that prohibits the patenting of natural materials.

When DNA is used as a chemical compound to produce recombinant drugs and vaccines the chemical analogy is valid and useful. For example, recombinant drug production involves creation of a nucleic acid that didn’t previously exist in nature (cDNA), which is then used to produce another, medically valuable chemical.

Enormous investments are required to develop, test, and obtain regulatory approval for pharmaceutical products. Patents on the human genes used to manufacture new drugs are central to the process of obtaining the necessary risk capital to introduce these important therapeutic agents into medical practice.

By contrast, genetic testing simply involves examining patients’ DNA sequences for variants that may predispose them to disease, predict response to drug therapy, or signal a possible susceptibility to pharmacologic side effects. Technical advancements have made the process of setting up genetic tests straightforward, inexpensive, and routine using existing, justifiably patented instruments and techniques. The Human Genome Project has made reference sequences, with which patients’ DNA sequences are compared, freely available. Consequently, gene patents in the genetic testing context decrease innovation in test development and limit the number of test providers, thereby raising healthcare costs and reducing or eliminating patient opportunities to confirm results.

Current U.S. law does not appear to permit patents on human genes, or patents on correlations between genetic variants and clinical phenotypes, to be used to restrict diagnostic testing for genetic disorders. Dating back to litigation over Samuel Morse’s patents on the telegraph, U.S. law has not allowed the patenting of natural phenomena. The “natural phenomenon” doctrine, which is distinct from the “product of nature” doctrine discussed in the context of drug production, prohibits the patenting of laws of nature, like gravity or relativity, and biological relationships, like genotype-phenotype correlations.

If I want to perform a genetic test on myself, my sole aim is to extract the information contained within my genes and correlate that information with the likelihood that I will be afflicted with a clinical disease. I am not making or selling a drug. I am merely reading my genetic code in search of natural relationships, or phenomena, that long predate my existence.

Patent holders on genes, genetic variants, and their biological correlations are already using the threat of litigation to force laboratories to stop performing genetic tests for predisposition to, as well as likelihood of treatment response for, various forms of cancer.

As genetic testing moves into mainstream medicine, this legal scenario will begin to have much wider, more detrimental effects on healthcare in the U.S. Gene patents for drug production have been useful and societally beneficial. But it is in all of our interests that the scope of these patents not be extended to include genetic testing.

Roger Klein, M.D., J.D., is currently pursuing research on the legal implications of the Human Genome Project at the Yale University School of Medicine. E-mail: [email protected].

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