Patent pending person? Supreme Court to weigh in on human genes patent.

Soon after learning that his son had autism, Hollywood producer Jon Shestack ("Air Force One") tried to get researchers investigating the genetic causes of the disorder to pool their DNA samples, the better to identify genes most likely to cause that disorder. But his approach to scientists at universities across the country in the late 1990s hit a brick wall: They refused to join forces, much less share the DNA.

"Each thought they needed to hold on to it to publish and patent," Shestack said in an interview. "This seemed criminal to us."

The U.S. Patent and Trademark Office has granted patents on at least 4,000 human genes to companies, universities and others that have discovered and decoded them. Patents now cover some 40 percent of the human genome, according to a scientific study led by Christopher Mason of Weill Cornell Medical College. But if foes of gene patents have their way, that percentage could be rolled back to zero.

On Monday, the U.S. Supreme Court will hear oral arguments in a case that calls into question whether human DNA can be claimed as intellectual property, and remain off limits to everyone without the permission of the patent holder.

The lawsuit, filed in 2009 by the American Civil Liberties Union and the Public Patent Foundation, challenges seven patents held by Myriad Genetics Inc on two human genes linked to breast and ovarian cancer. A federal judge said the patents were invalid. An appeals court overruled that decision, and the case landed in the Supreme Court.

The legal issues center on whether the genes that Myriad patented, called BRCA1 and BRCA2, are natural phenomena. The ACLU says human DNA is a product of nature, and as such not patentable under the Patent Act. Myriad argues that its patents are for genes that have been "isolated," which makes them products of human ingenuity and, therefore, patentable.

As scholars debate the legal questions, two parallel issues have emerged: whether patenting genes thwarts scientific research, and whether it harms patients.

A coalition of researchers, genetic counselors, cancer survivors, breast cancer support groups , and scientific associations representing 150,000 geneticists, pathologists and laboratory professionals argue that gene patents can be problematic on both counts. The American Medical Association, the American Society of Human Genetics, the March of Dimes and even James Watson (co-discoverer, in 1953, of the double helix), among others, have filed briefs asking the court to invalidate Myriad's patents on genes called BRCA1 and BRCA2.

On the other side are Myriad and industry groups such as the Biotechnology Industry Organization (BIO) and the Animal Health Institute, which say that if gene patenting is ruled invalid, companies - with no guarantee they could profit from their discoveries - would stop investing in genetics research, to the detriment not only of patients but the economy.

Scientific research
Gene patent opponents say studies and surveys show that such patents tie the hands of scientists and thwart research.

A 2010 investigation by an advisory committee to the U.S. Department of Health and Human Services found that patent holders had barred physicians and laboratories from offering genetic testing for hearing loss, leukemia, Alzheimer's, Huntington's disease, a heart condition called Long QT syndrome and other disorders affected by patented genes.

In a 2003 survey, 53 percent of the directors of genetics labs said they had given up some research due to gene-patent concerns. And in 2001, 49 percent of members of the American Society of Human Genetics said their research had to be limited due to gene patents.

"The overabundance of gene patents is a large and looming threat to personalized medicine," Cornell's Mason said. "How is it possible that my doctor cannot look at my DNA without being concerned about patent infringement? Individuals have an innate right to their own genome, or to allow their doctor to look at that genome, just like the lungs or kidneys."

Mark Capone, president of Myriad's laboratory division, counters that gene patents, by rewarding research, help patients. He said scientific research has not been hindered by the biotechnology company's patents, citing 18,000 scientists who have published 10,000 papers on BRCA.

"These are among the most studied genes in the world," Capone said.

"We've been able to save thousands of patients' lives" by telling patients they have cancer-causing BRCA mutations, he added.

The BIO industry group supports Myriad, saying patents are crucial to "the development of therapeutic, diagnostic, environmental, renewable energy, and agricultural products," and without patent protection such scientific discoveries would not be made.

Gene variants
The BRCA1 and BRCA2 genes account for most inherited forms of breast and ovarian cancer. They can be used to detect risk, and aid in treatment options.

Myriad has sole access to its proprietary database of BRCA sequences, which show whether a particular DNA change is dangerous. In 2004, Myriad stopped sharing that information with a breast cancer database run by the National Institutes of Health. Capone said the company was concerned that the information was being used not for research purposes, as intended, but to guide patient care.

Critics say the move has impeded research on BRCA, in particular studies to figure out the significance of rare variants and how such anomalies interact with other genes to increase or decrease the risk of cancer.

"Myriad's exclusive control has led to the misdiagnosis of patients and has precluded the deployment of improved genetic tests," said Lori Andrews, a law professor at Chicago-Kent College of Law, who wrote the American Medical Association's brief to the Supreme Court.

Geneticist Wendy Chung of Columbia University Medical Center cites the example of three sisters who sent their DNA samples to Myriad for BRCA analysis several years ago. The result was ambiguous: the women had a "variant of unknown significance" so they elected to have prophylactic mastectomies in case the mutation was cancer-causing. The women were very unhappy when, years later, Myriad re-classified the variant as innocuous.

"I think we could have moved a lot faster if the country's scientific brainpower could have analyzed patients' BRCA" rather than rely on Myriad, said Chung. Independent scientists could have studied not only whether a variant is dangerous or benign but also whether that risk is modified by the presence of other genes — crucial information when a woman is agonizing over whether to have her breasts removed, she said.

Capone said Myriad was not familiar with Chung's patients, but when a woman has a BRCA variant of unknown significance, the company recommends that she be treated according to her family history - aggressively if many close relatives have had breast or ovarian cancer, conservatively if not.

Myriad acknowledges that it has restricted what BRCA tests patients can get. For instance, since 1996 its standard test (which now costs $3,340) has looked for simple mutations in the BRCA genes, analogous to a misspelled word. Until 2006 it did not probe for large rearrangements in the DNA, which are analogous to moving big blocks of text from one page of a book to another.

The company, which has a market value of around $2.1 billion, has seen its shares fall about 13 percent since the Supreme Court decided on November 30 to take up the case.

It won a similar case in Australia in February, when the country's Federal Court ruled that Myriad and Melbourne-based Genetic Technologies Ltd had the right to hold a patent on BRCA1. Trial judge John Nicholas found the material could be subject to a patent because it could not exist naturally on its own, inside or outside the human body.

The Australian findings are unlikely to influence the U.S. case. Justice Nicholas said evidence presented in Australia was different to evidence in the U.S. case, and there were also different constitutional settings for patent laws.

The case is Association for Molecular Pathology, et al. v. U.S. Patent and Trademark Office, et al