Two firms are battling over the technology behind this compact nanopore sequencing device made by Oxford Nanopore Technologies.

Two firms are battling over the technology behind this compact nanopore sequencing device made by Oxford Nanopore Technologies.

Gene sequencing technology sparks a patent fight shrouded in mystery

The inexpensive and portable approach to DNA analysis known as nanopore sequencing has just begun to take off, but it has already sparked a legal battle between an industry giant and a high-profile upstart. Last week, Illumina, Inc.—which dominates the genetic sequencing industry—sued Oxford Nanopore Technologies, the first company to market a commercial nanopore platform. Illumina claims that Oxford’s two flagship devices infringe on patents that Illumina controls.

The battle, closely watched by researchers who already rely on Oxford’s products, hinges on the details of a technology that are still secret, and could lead the two firms into a murky corner of patent law.

Illumina leads the sequencing market, selling refrigerator-sized devices that read DNA by building and piecing together short complementary strands that bear chemical tags. In contrast, nanopore sequencing—which has been hailed as a game-changing approach to DNA analysis because of its simplicity and portability—reads long strands of DNA in a single pass, by measuring changes in electrical current as each nucleotide passes through a microscopic pore. Since 2014, Oxford has made its handheld MinION nanopore device available to researchers through an early access program, and is preparing to debut a larger and more powerful model called PromethION.

Illumina, meanwhile, has yet to release a nanopore platform, but it has licensed two key patents from the University of Washington, Seattle, and the University of Alabama, Birmingham. Those patents describe a system using bacteria-derived pores known as Mycobacterium smegmatis porin (Msp). In the new lawsuits, filed 23 February with the U.S. International Trade Commission and in a Southern California federal district court, Illumina contends that this Msp pore also underlies Oxford’s products.

But the exact contents of Oxford’s machines are still a mystery, even to the researchers who have been using them. “No one I know has any specific idea about what the pore is,” says Winston Timp, a biomedical engineer at Johns Hopkins University in Baltimore, Maryland.  It’s clear that Oxford has worked with Msp pores and made them available to researchers: Among the evidence Illumina provides in the lawsuit is Oxford’s patent on a mutated form of Msp; it claims the pore makes it easier to identify the nucleotides passing through. There’s also a recent paper, which acknowledges Oxford for providing Msp pores to Harvard University researchers.  But Timp notes that the company also holds patents on other types of nanopores, including some synthetic pores developed in his lab that aren’t derived from bacteria. And the illustrations in the company’s promotional materials, he notes, look more like the α-hemolysin, a different bacterial pore developed before Msp pores.

If the Oxford devices do contain an Msp pore, does that mean the company has infringed on Illumina’s patents? Not necessarily, says Dan Burk, a law professor at the University of California, Irvine. Illumina’s chance of winning the case might come down to a “very messy” aspect of patent law called the doctrine of equivalents, he says. The doctrine holds that a party can be liable for infringement even if their product doesn’t literally match what’s described in a patent, provided their product performs the same function, in the same way, to achieve the same result as the patented invention.

“It’s supposed to be a way of bringing some fairness into the system, because … it’s hard to capture exactly what you’ve invented in words sometimes,” says Arti Rai, a patent law expert at Duke University in Durham, North Carolina. If Oxford’s pore contains a different set of mutations than those in Illumina’s patents, a jury might be asked to determine whether there has still been infringement by equivalents. “It’s a very fuzzy doctrine, to put it mildly,” Rai says, and judges have recently seemed reluctant to allow the argument in court.

In all likelihood, the two companies would reach a settlement before that point, she adds. But if Oxford choses to fight, it could try to show that its technology doesn’t infringe by revealing what’s under the hood of its devices to the jury, and to Illumina’s lawyers. For Illumina’s researchers, and the scientists already making use of the sequencers, that technology could still remain a mystery.

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