As New Data Shrink Gene Pool, Patent Suits May Be Next Splash
In the quest to cure disease, companies are spending millions of dollars to scour human DNA and find crucial, tiny segments known as genes. On Monday, that job got far easier.
Two competing teams of scientists laid out new information about where genes tend to be clustered in the vast expanse of DNA. Equally important, both teams said they believe that humans have only about 30,000 genes, far fewer than the 100,000 or more that many experts had expected.
“Every one of the searches [for a gene] is like looking for a needle in a haystack,” said Dr. Francis S. Collins, leader of one of the teams. “Well, guess what? The haystack just got three times smaller.”
But while genes may be easier to find, researchers found a potential dark side to the news: It could bring chaos to the process of patenting genes, which in turn could slow the process of turning genes and their products into new cures for disease. Because companies usually want to have secure ownership rights to genes before investing the millions of dollars it takes to develop drugs from them, doubts about patent rights could have far-reaching effects.
“I think there are lots of suits to be filed, and this will make it more so,” said Dr. Robert H. Waterston, a DNA-mapping specialist at Washington University in St. Louis.
“The fewer the number of genes, the greater the likelihood that patent collisions will occur,” said Collins, director of the National Human Genome Research Institute at the National Institutes of Health. “If we had found 150,000 genes, that would be a little less likely.”
An official with the U.S. Patent and Trademark Office said that the fears are exaggerated and that the office has rules that will keep competing patents to a minimum.
The two teams concluded independently that humans have fewer genes than expected after conducting the first thorough surveys of the full complement of human DNA.
One team, led by J. Craig Venter of Celera Genomics Corp., found strong evidence of 26,383 genes and weaker evidence for an additional 12,731.
The other team, an international consortium funded mostly by the U.S. government and a British charity, said there are probably about 35,000 genes, but possibly as many as 40,000. The Celera team published its findings in the journal Science; the international team published in Nature.
But in a potential wrinkle for the patent system, the teams also found that many genes produce multiple proteins.
Scientists once believed that each gene produced a single protein, which in turn performed some task in the body, such as signaling hunger, metabolizing food into energy or attacking a foreign virus. When genes go awry and produce faulty proteins, the result is often disease.
But it turns out that each gene produces three proteins on average, and sometimes as many as five, the international team reported.
Some researchers said this suggests that two scientists or companies, while researching different proteins involved in different diseases, likely have sought to patent portions of the same gene. The result could be a clash over patents that blocks one or both companies from continuing their research, producing a drug or developing a genetic test for disease, they said.
“I think it could inhibit research,” said Arthur Caplan, a bioethics professor at the University of Pennsylvania and an advisor to Celera. “The question that will face companies is: What does corporate responsibility require that you do in terms of sharing access, making the information you own available? They’re going to have a stewardship responsibility, because they work in health. This is not like patenting Coke.”
If a flare-up of patent clashes “hasn’t happened yet, it’s going to happen soon,” said Dr. Lee Hood, a molecular biologist at the University of Washington in Seattle. “I think there will be genes with 10 or 50 different [protein] forms. . . . You will have patents for every splicing and, how that gets untangled, God only knows.”
The patent office estimates that it has issued patents on about 1,000 full-length human genes, but it has tens of thousands of applications pending.
Some patent lawyers and scientists said that competing patent claims do not necessarily foreshadow court battles. “To say progress is going to stop is too extreme,” said Scott Brown, chief patent counsel at Millennium Pharmaceuticals Inc. in Cambridge, Mass. When necessary, he said, companies will sign licensing agreements so that they can use parts of genes owned by other companies. “In the past, reasonable minds have prevailed.”
John Doll, director of biotechnology for the patent office, said the fears are overstated.
He said that if a company patents a protein and a gene but is not aware the gene produces a substantially different second protein, then another company would be free to patent that second protein without colliding with the ownership rights of the first company. In short, he said, the first company could not claim patent rights to what it had not discovered and isolated.
“The case law on this has been around for 200 years,” Doll said.
However, patent lawyers said that the prospect for lawsuits depends on how broadly the claims in patents are written. Even when two valid patents are issued, they said, one owner may be able to win a lawsuit blocking another from moving ahead with research or with a drug.
In at least one recent case, critics have challenged whether a company was granted overly broad patent rights. In June 1995, Human Genome Sciences Inc. applied for a patent on a gene and protein involved in cancer, blood disorders, allergies and arthritis. By the time the patent was issued last year, researchers elsewhere also had found that it played a role in AIDS.
Critics complained that Human Genome Sciences had been granted patent rights for the gene’s role in AIDS without sufficient proof that it understood that role, a charge that the company vigorously denied.
Brown, of Millennium Pharmaceuticals, said that the new findings on gene function could be a positive force in research, not a negative one. By showing that there are many proteins out there yet to be patented, it could open the door to new players in drug research.
“If they can find the variant of the protein that is really the key to treating people, then they’re in the game,” Brown said. “If anything, this is good news, because it says there is still opportunity to obtain patents.”
