A federal court has ruled that key patents held by Myriad Genetics, a diagnostics company based in Salt Lake City, UT, on the BRCA 1 and 2 genes are invalid. Specific mutations in these genes are responsible for the majority of hereditary forms of breast and ovarian cancers, and many women with a family history of these cancers undergo screening to help them make medical decisions around preventing the disease.

The suit, brought by the American Civil Liberties Union (ACLU), patients and medical groups, argued that the patents restricted research and patients' access to healthcare. Myriad's critics have long argued that they give the company a monopoly over this type of genetic screening, allowing it to keep prices high--the test costs more than $3000, despite continual decreases in the cost of genomic analysis tools--and preventing women from seeking confirmatory tests from other sources.

According to a statement from the ACLU, "The precedent-setting ruling marks the first time a court has found patents on genes unlawful and calls into question the validity of patents now held on approximately 2000 human genes." That amounts to about 20 percent of human genes, including those associated with Alzheimer's disease, colon cancer, asthma and other illnesses. "Because the ACLU's lawsuit challenges the whole notion of gene patenting, its outcome could have far-reaching effects beyond the patents on the BRCA genes."

Dan Vorhaus at the Genomics Law Report discusses the ruling in more detail:

Judge Sweet's ruling invalidates both Myriad's composition of matter claims (its patents on isolated DNA sequences to all or a portion of the breast cancer genes) and its method claims (those patent claims that relate to analyzing or comparing isolated DNA sequences in order to detect mutations in a patient's BRCA1/2 genes that might cause breast cancer).

The overall tone of the Court's ruling is best captured by this passage (from page 135):

The identification of the BRCA1 and BRCA2 gene sequences is unquestionably a valuable scientific achievement for which Myriad deserves recognition, but that is not the same as concluding that it is something for which they are entitled to a patent.

The ruling follows decades of debate over gene patenting. An article in the New York Times points out that such patents "have been granted for decades; the Supreme Court upheld patents on living organisms in 1980," an argument Myriad made when asking the court to dismiss the case. The company is expected to appeal the decision

Many patent experts were surprised by the court's decision and predict it will have a negative impact on young start-ups in the biotech industry. It's not yet clear how it will affect the market for BRCA screening. "For the moment, however, we do not foresee this decision producing any radical changes in commercial, clinical or other activity surrounding Myriad's BRCA patents, or gene patents more broadly," Vorhaus wrote in his post.

In the broader policy debate surrounding gene and biotechnology patents, however, this decision is the latest, unmistakable shot across the bow of gene patent holders, particularly those such as Myriad Genetics that have developed businesses around patent-protected genetic tests supported by exclusive rights in underlying gene patents.

Incorporating common genetic risk factors into the models typically used to calculate a women's breast cancer risk has little impact on clinical decision-making, such as whether an individual should consider earlier or more frequent mammography or prophylactic drugs, according to a paper published today in the New England Journal of Medicine. The results follow similar studies for diabetes and cardiovascular disease, echoing what has now become a common criticism of genome-wide association studies; that this approach is unlikely to identify genetic risk factors of diagnostic value.

Over the last few years, researchers have used DNA-studded microarrays to quickly search tens of thousands of human genomes for common genetic variations linked to various diseases, dubbed genome-wide association studies. Despite the enormous size of these studies, they have only identified a fraction of the source of the genetic risk of disease. And the vast majority account for a very small change in risk in a given individual. (This is in contrast to rare genetic variants, like BRCA1, which substantially increase a women's risk of developing breast cancer.)

To analyze the potential impact of common, breast cancer-linked variations, researchers from the National Cancer Institute combined data from five studies of breast cancer. Taken together, these studies compared 5,590 breast cancer patients to 5,998 women without cancer, mostly white and age 50 and 79. The team employed a commonly breast cancer risk model, which uses medical, reproductive and family history, to calculate an individual's risk of developing cancer over the next five years. They found the risk score was similar to that calculated using 10 breast cancer variations recently identified in genome wide association studies. But combining the two risk models had little impact. "When we included these newly discovered genetic factors, we found some improvement in the performance of risk models for breast cancer, but it was not enough improvement to matter for the great majority of women." said Sholom Wacholder, Ph.D., senior investigator in NCI's Division of Cancer Epidemiology and Genetics (DCEG), in a statement.

For most women in the study, the inclusive model did not substantially change their personal estimated risk of developing breast cancer beyond the Gail model calculations. Overall, using the inclusive model reclassified 26 percent of women to a higher risk category; 28 percent to a lower risk category; and left 46 percent in the same category of risk score. The shifts from one category to another were generally too small to influence clinical decision-making.

That's probably not welcome news to direct-to-consumer genetic testing companies, such as Navigenics and DecodeMe, which screen for these types of variants. Kari Stefansson, founder of Decode, argues that the results do show that common variants are useful, but that we still have a way to go.

My hope is that this entire argument is soon moot. Whole genome sequencing, which can identify both rare and common variants, seems finally poised to fulfill its role in illuminating the genomics of disease. A handful of papers published over the last few months have demonstrated that sequencing can identify genetic variants linked to some rare diseases, and scientists hope the same approach can be applied to more common ones. While a $48,000 genome sequence--the cost of Illumina's personal sequencing service--is still a lot compared to Decode's $500 cancer screen, the price is dropping rapidly. (No one knows yet how much more bang you'd get for your buck.) Complete Genomics, a startup in California, will soon offer bulk sequencing services for about $20,000 a genome, with a $5,000 price tag not far behind.

A new microfluidic device (above), developed by scientists at the University of Toronto, can measure estrogen levels in very small samples of tissue. The device, which will be used to monitor breast cancer patients, uses digital microfluidics, in which discrete droplets (colored with dyes in the picture) are manipulated on an open surface by application of electrical potentials to an array of electrodes. Credit: Aaron Wheeler

A microfluidics chip that can easily detect estrogen levels in breast cancer patients could give physicians a new way to monitor the disease. The chip, developed by scientists at the University of Toronto, uses electrical signals to move droplets of fluids around a microfluidics circuit, and it requires a blood or tissue sample 1,000 times smaller than that required by current methods. "If the technique becomes widely available, we could replace biopsies with pinpricks," says Aaron Wheeler, an engineer at the University of Toronto who developed the device.

The hormone estrogen plays a large role in many breast cancers, encouraging the growth of breast cancer cells. Some drugs such as Tamoxifen specifically block estrogen activity. The ability to routinely measure estrogen in breast tissue could give physicians a way of monitoring the effectiveness of cancer drugs, and it might even help assess the risk of recurrence or of developing the disease. "We have solid evidence that measuring estrogen inside the breast is important," says Noha Mousa, a physician at the University of Toronto who helped run the study. "If there is a high estrogen level, we know the drugs are not doing their job, and there is a likelihood of recurrence." However, estrogen isn't routinely measured in breast cancer patients because it requires a substantial tissue sample acquired through a painful and invasive biopsy.

Because the new chip takes such small samples, tissue can now be collected via a whisper-thin needle. In addition, the chip can measure estrogen levels in blood, saliva, or tissue, eliminating the preparation steps required by existing methods. "This device is the first we are aware of to accept raw unprocessed tissue as input, which we believe will eventually allow very quick turnaround," says Wheeler.

The device is still considered experimental, but Wheeler says his group is looking for funding to build a commercial prototype of the technology. He envisions two versions--one that would be used in a lab, and a smaller, point-of-care device that could be used in a doctor's office--and expects a commercial version to be available within the next five years.

Mousa plans to use the chip in a clinical trial funded by the Canadian Breast Cancer Foundation to measure hormone levels before and after treatment. "I believe this method will be useful for many applications in women's health," she says. "We can apply the same technique to many other steroid hormones."

She also hopes to use the technology to determine if estrogen levels in breast tissue of healthy women at risk for breast cancer can help predict their risk. "We have not been able to do that in healthy women because it requires taking a big sample," she says.