Prenatal Testing Using Maternal Blood
An emerging clinical area for DNA sequencing involves analysis of fetal DNA circulating in a pregnant women's blood to identify genetic disorders of the developing child. Since 1970, when researchers at Stanford University discovered a few cells in a pregnant woman's blood that must have come from her developing son since they contained male Y sex chromosomes, there has been the idea to evaluate fetal genetics through some sort of maternal blood test.
However, fetal cells circulating in maternal blood are rare—about 1000 cells per quart of blood whereas there are about 5 billion red cells and 5 million white cells in the same volume. Isolating these fetal cells for routine analysis would be challenging. However, it turns out there is also a lot of cell-free fetal DNA just floating around in maternal blood. With recent advances in DNA sequencing technology, this fetal by-product can be isolated and analyzed. This approach finally provides a practical technique for prenatal genetic analysis using a sample of blood extracted from pregnant woman.
Boy or Girl—a Simple Blood Test Will Tell
Prenatal tests for gender determination using maternal blood have been available for a few years, such as the web-based blood test offered by Prenatal Genetics Center or the drug-store test offered by Consumer Genetics. These are not FDA approved tests since the results are not used for medical purposes, so there are few regulatory guidelines. A recent study, however, does indicate they are typically accurate.
Down's Syndrome—a Simple Blood Test Will Tell That Too
Actual prenatal clinical diagnostic tests using maternal DNA just became generally available at the end of 2011 now that they have completed clinical trials. Five companies are pursuing this emerging niche market.
The first-to-market product was from Sequenom which launched their maternal blood test—MaterniT21 LDT—for detection of trisomy 21, the chromosome anomaly that causes Down's Syndrome. The test also detects trisomy 18 and 13 chromosome abnormalities.
In February, just a few months after Sequenom's launch, Verinata Health (formerly, Artemis Health), who received close to $50 million in third-round venture funding in mid-2011, launched its Verifi test. Then, in May, Ariosa Diagnostics (formerly Aria Diagnositcs), who also just finished a third round of financing for $50 million, launched the Harmony Prenatal Test. Both of these tests identify the same chromosomal abnormalities as the Sequenom test.
Natera (formerly, Gene Security Systems), who recently received $20 million more in a fourth round of venture financing, still have their PreNATUS test in clinical trials. They claim their test will detect a broader range of abnormalities than the three currently available tests. While they presented promising results at the American Society of Human Genetics in November 2012, they did not launch the approved diagnostic kit as of the end 2012.
Patent Wars: Who Can Use Maternal Blood for Prenatal Tests
As might be expected with several companies offering similar products with similar technology to the same market, initial produce launches were greeted by a series of rapid fire patent infringement filings. Soon after MaterniT21 hit the market, both Ariosa and Natera filed suit against Sequenom for infringement. Sequenom promptly responded with their own legal filing against both Ariaosa Diagnostics and Natera to try to block the launch of their kits. Then, in February, Verinata jumped into the fray and filed suit against Sequenom.
This leaves a configuration where the three silicon valley start-ups are pointing fingers at Sequenom who is trying to shut them down. One of these companies' claims of interference, probably Verinata's, has convinced the US patent office to delayed issuance of a recent Sequenom application that was approved and due to issue in December of 2012. So far, LifeCodexx, in Germany, has been fortunate enough to stay out of the scrap.
The Battle for a Developing Market
As an 17 year old public company with over $50 million a year in revenue from gene sequencing technology, Sequenom is the heavyweight in this game. It is not surprising the smaller venture enterprises in the San Francisco area are lining up against it. While it is certainly unclear how the battle will sort out, it is clear that an extended multi-party patent fight could be detrimental to all companies involved. Recently, researchers at the Stanford Center for Bioethics expressed this concern in detail in the journal Science Translational Medicine.
However, even without the intellectual property issues, it seems unlikely this market niche can support five companies with such closely aligned products and business strategies. It will be interesting to see how each enterprise manages the commercial and legal pressures while expanding the technology to detect a broader range of more subtle genetic variations in the race to capture the lion's share of this diagnostic niche.