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EPO Upholds Molecular Devices’ Automated Electrophysiology Patent; Nanion to Appeal

Molecular Devices this week said that the European Patent Office has upheld one of its patents related to automated electrophysiology more than four years after competing automated patch clamp vendor Nanion Technologies filed an opposition claiming that the patent was too broad.
The EPO’s decision could bolster Molecular Devices’ electrophysiology IP portfolio in Europe, which may be important for the company because the majority of its automated electrophysiology rivals – such as Nanion, Flyion, and Sophion Biosciences – are located on that continent.
However, Nanion said this week that the EPO’s decision is not final and is only an “intermediate step” in an ongoing process, and that it fully intends to file an appeal – despite the fact that the technology covered in the patent has no direct bearing on its current product line.
The patent, EP 1,040,349, entitled “Positioning and electrophysiological characterization of individual cells and reconstituted membrane systems on microstructured carriers,” was awarded in 2001 to Ecole Polytechnique Fédérale de Lausanne in France, according to EPO documents.
Inventors on the patent, which can be seen here, are Horst Vogel, a professor of physical chemistry at EPFL, and Christian Schmidt, a founder of EPFL spin-out biotech Cytion. Molecular Devices acquired Cytion – and its share of the ‘349 patent – in 2001. According to EPO documents, Molecular Devices was assigned full ownership of the patent through an agreement with EPFL last year.
According to its abstract, the patent relates to “a measuring device [that] permits a very simple positioning of cells and vesicles respective of cell membranes on planar carriers.” The patent further claims “a corresponding highly efficient method for the positioning and electric characterization of such membranes with a consistently high signal-to-noise ratio.”
Nanion, a 2002 spin-out from the University of Munich, has questioned specific claims regarding the positioning of cells. Essentially, CEO Niels Fertig said, the patent claims are far too broad.
“The reason we objected to the patent is that it actually relates to a way of positioning cells by electric fields,” Fertig told CBA News this week. “It is not a device patent claiming a device for automated electrophysiology, as such.”
Positioning cells near an electric field, usually on a silicon chip, in order to make electrophysiological methods is also known as planar patch clamping. This is opposed to traditional patch clamping, which creates an electrical seal using a pipette.
“There has been substantial prior art in using planar systems for doing electrophysiology,” Fertig said. “We clearly see that this is not an invention of device, because it is an inherent property of any potential chip design you can think of that if you apply voltage across a field, a chip having a hole in a conducting media will actually have a focusing effect of the electric field at the opening.
“That is an inherent property – nothing that is inventive,” Fertig said. “It is only potentially inventive to use this force for the positioning, so it is a method, not the device. That’s our understanding.”
The EPO, however, does not see it that way, according to Molecular Devices. In a statement this week, the company said that “the three-person opposition board of the EPO examined the request and delivered a final opinion rejecting all grounds for the opposition on Dec. 7, 2006.”
According to Fertig, this comes as a surprise to Nanion, which will “certainly” file an appeal. In fact, this week following Molecular Devices’ statement, Nanion released its own statement announcing its continued opposition.
“This has been an ongoing process for the last four years or so,” Fertig said. “There were only written records and statements going back and forth with the European Opposition Board, and those were very positive that this patent is too broad and should be revoked, or at least diminished. It was only during this [latest] opposition hearing that they made this very surprising decision.
“In any case, this is now their decision,” he added. “It is an intermediate step, and there will be an appeal.”
Cornering the Market
Nanion markets two platforms for automated electrophysiology: the Port-a-Patch, which is a miniaturized patch clamp device with a small footprint for investigating one cell at a time; and the Patchliner, which is a fully automated system with a liquid-handling robot and multiple recording channels for higher throughput studies, Fertig said.
Molecular Devices also sells two main automated electrophysiology platforms: the PatchXpress 7000A, which is intended for lower-throughput, higher quality automated patch clamping; and the IonWorks Quattro, a high-throughput instrument based on population patch clamping.
It is unclear how the technology described in the patent relates to any of these instrumentation platforms. Calls and e-mails to Molecular Devices were not returned in time for this story.
According to Nanion, the IP does not necessarily relate to any of its products. Fertig told CBA News that there are several differences between Nanion’s and Molecular Devices’ products – the most important being Nanion’s microfluidic component that Fertig said enables rapid and flexible pharmacological profiling.
Fertig also said that Nanion strives to record “very high-quality” data, while Molecular Devices’ products seem to be more suitable for lower-quality but higher-throughput industrial applications.

“It’s more a principle thing, that we don’t want this patent to be further or too far in its reach than what is actually invented. It’s not that it really limits our technology.”

“It’s not that we really rely on this method,” Fertig said. “It’s simply that the claims made in the patent are much too broad. It’s more a principle thing, that we don’t want this patent to be … too far in its reach than what is actually invented. It’s not that it really limits our technology.”
Torsten Freltoft, CEO of competing high-throughput electrophysiology company Sophion Bioscience, agreed with Fertig. “It’s my belief that Nanion’s products are not infringing in any way” on Molecular Devices’ patent, Freltoft told CBA News this week. “As far as I know, nobody in the world, not even Molecular Devices, is using the technique covered in the patent.”
In any event, Nanion’s is the sole formal opposition against the patent, as other competing high-throughput electrophysiology vendors, such as Denmark’s Sophion and Germany’s Flyion, have not filed their own oppositions with the EPO. According to Michael Fejtl, Flyion’s chief scientific officer, Nanion may be involved in the dispute because its technology is at least somewhat similar to Molecular Devices’ technology.
“On some issues it’s certainly interesting for us, but on the other hand, it’s not terribly important from our side,” Michael Fejtl, Flyion’s chief scientific officer, told CBA News. “I’m aware that the reason for the patent dispute is simply because both [MDCC and Nanion’s] high-throughput assays depend on planar patch-clamp technology, and that of course is not the case for Flyion, which has its own patents using classical patch electrodes … [to] patch cells from the inside.”
Sophion’s Freltoft said that the technology in question does not affect his company’s technology. He also said he believes neither Nanion’s nor Molecular Devices’ currently marketed technologies are relevant to that described in the patent.
“This approach really has to do with a way of positioning cells in a patch clamp setup,” he added. “This way of doing it by electrical forces really doesn’t work in practice. Nobody really cares about the patent except Molecular Devices somehow, because they make a big fuss about having won this dispute.
“Of course, you don’t know if some activity or development in the future might have gone that way if the patent had been [revoked],” said Freltoft. “But we have no plans whatsoever to do anything in that respect, and I don’t know if other companies have.”
As for the notion that the EPO’s decision would give Molecular Devices a firm hold on both the North American and European automated electrophysiology markets, Fertig said: “It’s not that this patent, even in its current form, is so broad that there would not be room for other technology.”

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