NEW YORK – With an appellate court victory on Wednesday on top of two others earlier this month, Ravgen continued its winning streak in litigation over patents covering methods for identifying genetic abnormalities in newborns using a maternal blood sample.
On Wednesday, the US Court of Appeals for the Federal Circuit upheld a favorable decision for Ravgen and against Laboratory Corporation of America in a review of US Patent No. 7,727,720, held by Ravgen, by the US Patent and Trademark Office's Patent Trial and Appeal Board (PTAB). Early in the month, the same court upheld a PTAB decision for Ravgen in response to a challenge by Labcorp over the validity of US Patent No. 7,332,277 also held by Ravgen. And on Jan. 22, the court upheld another PTAB ruling for Ravgen in a challenge to the '277 patent by Streck.
Both the '277 and '720 patents are titled "Methods for Detection of Genetic Disorders" and are at the center of the litigation involving Ravgen.
The small Baltimore-based diagnostic testing firm began years of litigation in 2020 with patent infringement lawsuits against eight test makers to secure royalties over commonly used methods of sampling fetal DNA from a maternal blood sample. Meanwhile, the firm negotiated with about a dozen other companies over similar infringement claims.
Ravgen secured a $273 million verdict in 2022 in its case against Labcorp, a subsequent ruling in 2023 for $100 million in enhanced damages against Labcorp, and a $57 million verdict in 2024 against Natera. It also reached settlements in past years with Illumina, Quest Diagnostics, Myriad Genetics, and PerkinElmer, now called Revvity. In September 2024, Ravgen reached two more settlements with Biora Therapeutics, formerly named Progenity, and Roche subsidiary Ariosa. The terms of the settlements were not disclosed.
Ravgen also fended off a flurry of challenges to its patents through 10 inter partes reviews by the PTAB. While Ravgen prevailed in those reviews, Labcorp and blood collection tube maker Streck filed appeals.
In their appeals, Labcorp and Streck had argued that Ravgen's patents described methods that were too obvious to be patentable based on prior research, and they said that PTAB had erred in its analysis of the evidence.
While Streck does not make NIPTs, the company sells blood collection tubes to most of the firms that have been sued by Ravgen, and Streck sought a PTAB review of the '277 patent on the use of an agent to inhibit cell lysis during the sampling of fetal DNA from a maternal blood sample. That PTAB review led to a 2023 ruling that upheld the issuance of the patents.
Labcorp and Streck did not respond to requests for comment.
Ravgen attorney Kerri-Ann Limbeek said that the firm is happy with the recognition that, through settlements and trial verdicts, its technologies have been valuable.
However, she noted that Ravgen's district court lawsuits against Labcorp and Natera remain in proceedings over post-trial motions, and those firms could file additional appeals in each of the cases. If that happens, she expects that it could take about two years for judgments in each case to be finalized. Any payments from Labcorp and Natera remain on hold while litigation continues, she said.
"It does underscore that, especially for a small company like Ravgen, it's really hard to pursue this kind of litigation battle because it takes many years and a lot of work and a lot of challenges," Limbeek said.
By Ravgen's telling, the stakes in the lawsuits were also personal. The company said in court documents filed in 2020 that its founder, Ravinder Dhallan, was a former emergency room physician who became determined early in his career to develop better noninvasive prenatal diagnostic tests after his wife had three miscarriages.
At the time, the available noninvasive prenatal diagnostic tests had low sensitivity and low specificity, whereas using more accurate but highly invasive tests increased the risk of miscarriage.
While Chinese University of Hong Kong's Dennis Lo's team reported in 1997 finding cell-free fetal DNA in maternal plasma, which laid the groundwork for NIPTs, Raven said in court documents that the breakdown of maternal blood cells in a sample released an overwhelming amount of maternal DNA that inhibited the recovery of fetal cell-free DNA and detection of chromosomal abnormalities. Increasing the percentage of free fetal DNA relative to free maternal DNA in a sample would be necessary for the development of an accurate NIPT.
Dhallan founded Ravgen (Rapid Analysis of Variations in the Genome) in September 2000. His approach involved the use of an agent to impede cell lysis of maternal blood cells and the identification of ratios of alleles at locations that would indicate the presence of a chromosomal abnormality in the fetal cell-free DNA. Dhallan estimated that he spent millions of dollars on research into novel testing methods before he secured the '277 patent in 2008 and the '720 patent in 2010.
NIPTs caught on commercially not long after those patents were filed starting with the 2011 launch of Sequenom's MaterniT21 test for Down syndrome and the emergence soon afterward of various other tests, which led to a series of patent fights over the technologies.
Ravgen has said in court documents that it tried for years to form partnerships, including the licensing or purchase of the patents, with diagnostic companies for the use of its technologies. In 2022, Ravgen's lead counsel John Desmarais said that the company had still hoped to reach licensing to avoid litigation, but any seller of a noninvasive prenatal test was a potential target for a lawsuit or negotiations.
Ravgen's lawsuits were mostly focused on NIPTs, but the company's complaints also extended to other tests. In a lawsuit against Natera, for example, Ravgen had accused Natera's Panorama and Vistara NIPTs, Signatera circulating tumor DNA test, and Prospera cell-free DNA transplant rejection test of infringing on the '720 and '277 patents.
Limbeek said that Ravgen has secured five or six licenses for its patents without litigation and another six as a result of litigation. She declined to provide the terms of the agreements due to confidentiality agreements but said that the license amounts had varied depending on factors such as the number of infringing products and whether any of those products were research use only.
While Ravgen waits in anticipation of payments from Labcorp and Natera, the firm has been using some of the proceeds from its licensing agreements to help pay the high costs of litigation as well as to support ongoing operating costs, Limbeek said.
Another of Ravgen's lawyers, Brian Matty, noted that although Ravgen has endured challenges to the validity of its patents by some of the largest companies in the diagnostics industry, all of Ravgen's claims have been upheld. He added that the decisions in Dhallan's favor have provided validation that he invented an important technology.
Matty said that the companies that Ravgen has accused of infringement have made billions of dollars from those methods and Dhallan should receive his fair share.
"This is a unique case where we got to represent the little guy who, I think, had been beat up by some big companies over the past 20-some years," Matty said.