The case for and against the patenting of genes

Penn geneticist Haig Kazazian , in the laboratory. He and colleague Arupa Ganguly were asked by the ACLU to be plaintiffs in a case that could end gene patenting.
Penn geneticist Haig Kazazian , in the laboratory. He and colleague Arupa Ganguly were asked by the ACLU to be plaintiffs in a case that could end gene patenting.
Posted: June 21, 2010

In 1998, Penn geneticists Arupa Ganguly and Haig Kazazian were ordered to stop offering women a test for genetic mutations that carry a dire risk of breast cancer.

Myriad Genetics Inc. accused the researchers of patent infringement and threatened them with a lawsuit. They weren't even using a test patented by Myriad. Ganguly had pioneered a new way to read these genes and devised her own test.

But Myriad held a patent on the genes themselves.

Now both University of Pennsylvania scientists have been pulled into a lawsuit that could not only strip Myriad of its patents but end the 30-year-old practice of patenting human genes.

The lawsuit was filed in New York by the American Civil Liberties Union along with several medical associations and breast cancer activists.

The ACLU won the first round in March when federal Judge Robert Sweet ruled that Myriad's patents on genes called BRCA1 and BRCA2 were improperly granted. Myriad lawyer Richard Marsh said they filed for appeal on Wednesday. The case now looks likely to reach the U.S. Supreme Court.

A decision could invalidate several thousand patents on genes as well as thousands of other patents on diagnostic tests and natural products, say lawyers following the case.

Those in favor of DNA patents say if the ACLU gets its wish, it could devastate the biotechnology industry - especially if the ruling fans out to cover more than DNA.

Opponents say Myriad's aggression toward potential competitors has deprived women of the chance to independently confirm Myriad's test, which cost around $3,120 and is covered by most health insurance.

Women with mutations in these so-called breast cancer genes, BRCA1 and BRCA2, live with a 60 percent to 80 percent chance of getting the disease over their lives. BRCA2 mutations also lead to a high risk of ovarian cancer.

Doctors often advise these women to undergo a double mastectomy before they get cancer. For those with BRCA2 mutations, doctors sometimes recommend they have their ovaries removed as well.

Opponents are also troubled by gene patents on principle, since genes are not inventions, nor in most cases are they natural products used as a medicine.

Some scientists have long resented the Utah-based company holding the patents, Myriad Genetics Inc., and its founder, Mark Skolnick.

He was not favored to win the race for the breast cancer genes. The first person to realize that such a gene existed was a revered geneticist, Mary Claire King, now at the University of Washington.

Working with collaborators at Penn as well as Francis Collins, now director of the National Institutes of Health, she collected DNA from hundreds of women, proving BRCA1 existed by locating it on one arm of chromosome 17.

In 1994, using similar data from Utah families, Skolnick pinpointed the actual gene and won the race. His company was awarded multiple patents on the gene.

The following year, an international team found another crucial breast cancer gene, dubbed BRCA2. Skolnick's company purchased the patent rights.

Big questions still loomed, especially about how to interpret the test's results.

Testing required scientists to read the entire sequence of DNA making up BRCA1 and BRCA2, each one made from several thousand code characters. Within those are hundreds of possible spelling errors, only some of which will interfere with the function of the gene and increase cancer risk.

At Penn, Ganguly started a study aimed at improving BRCA testing. An expert on large genes, she found a new way of screening for mutations and developed her own BRCA test.

"We tested about 500 women a year," said Kazazian. It took a lot of work, he said. Then in 1998, Myriad's cease-and-desist letter killed the project.

"It was devastating," said Ganguly. "Three or four years of work had to be thrown away."

If she'd been able to continue, she said, her test could have offered a second opinion, something women who testified for ACLU claimed they couldn't get because of Myriad's patents.

She and Kazazian got a call from the ACLU two years ago asking them to be plaintiffs. Kazazian says he's not against all gene patenting - he owns several gene patents that have begun to bring in royalties. But he thinks such patents should be issued only when a scientist has found a particular use for a gene.

Patent law distinguishes more general patents from "methods" patents that cover a specific use, said Hank Greely, director of the Center for Law and the Biosciences at Stanford University.

Methods patents can apply to natural products - say, if someone finds that a substance from a plant works as an anticancer agent. Some gene patents are methods patents, he said, but others fall into a more general category called "composition of matter."

Those patents can also apply to products that exist in nature as long as the patent holders alter, isolate or purify them. With genes, he said, lawyers have made a case that the patent holders have isolated and purified them.

Myriad has a number of both kinds of patents on the BRCA genes, he said. "What you want if you're a patent holder is a broad spread of patents that basically tie up everything."

The company earned $84.6 million last year on revenues of $326 million, mostly for its BRCA tests.

The judge who ruled against Myriad in March argued that physical DNA wasn't the commodity that mattered - it was the information encoded in DNA that was important. And this information wasn't a patentable product.

"It's a very clever argument and one that's within the borders of existing case law," said Greely.

Methods patents, he said, are more straightforward and haven't attracted the same political outrage. The judge in the federal trial ruled Myriad's methods patents invalid as well. If Myriad can regain those, he said, the company can keep control of the breast cancer tests.

Ethicist Art Caplan of the University of Pennsylvania said the system allowed scientists to get patents before they had a useful product. To patent BRCA1, he said, Myriad didn't even have to produce a working test, let alone prove its test was accurate.

Stanford's Greely said the appellate courts are pro-patent so Myriad is likely to win the next round, likely sending the case on to the Supreme Court.

If that happens, it could affect more than just gene patenting, said Kevin Noonan, a patent lawyer at McDonnell Boehnen Hulbert & Berghoff and author of the blog Patent Docs. A ruling against gene patents could invalidate other patents on diagnostics as well.

Noonan said many arguments against gene patenting are emotional rather than rational - especially those voiced in a 2007 New York Times commentary by author Michael Crichton.

The piece implied that companies own the DNA all of us carry in our cells.

In addition to being absurd, Noonan said, such a scenario would violate the 13th Amendment, which prohibits slavery.

Most people, Noonan said, don't understand that patents last only 20 years before they expire. Myriad's patent on the BRCA genes will expire in 2014.

He also pointed to hundreds of research papers on BRCA1 and BRCA2, proving that the patents didn't stop other labs from doing research.

Noonan said one consequence of ending gene patenting will be increased secrecy. Patents allow their holders to publish their findings. The patent system "fosters disclosure," he said.

A draft study commissioned by the U.S. secretary of health and human services found no evidence that gene patents inhibited research, or that taking them away would matter either.

One point in Myriad's favor - the company has created a good test, said geneticist Richard Fishel, who studies colon cancer genes at Ohio State University.

It's a complicated test, said Fishel, and it's not obvious how to interpret the results. While there are dozens of possible cancer-causing mutations, there are also harmless ways the genetic sequences vary from person to person.

Myriad has spent years developing what's called bioinformatics - the creation of huge databases they can draw on to discern the cancer-prone versions of these genes from the healthy ones. Myriad has used the same techniques to develop genetic tests for colon-cancer risk.

Whatever the courts decide, the completion of the Human Genome Project a decade ago essentially stopped all new gene patenting by mapping and sequencing all as-yet-unpatented genes. That means the last gene patents will expire by 2020.


Contact staff writer Faye Flam at 215-854-4977 or fflam@phillynews.com.

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