Last week, GPCR assay company Euroscreen of Belgium obtained a new US patent covering the use of the luminescent protein aequorin in an assay procedure to screen modulators of calcium-coupled receptors, bolstering the company’s patent estate in the area of luminescent cellular assays.
The procedure, used to screen modulators of calcium-coupled receptors, is “very important but very simple,” according to Alfred Gray, Euroscreen’s vice president of business development. Instead of adding reagents to cells adhering to a plate, the method calls for the addition of cells in suspension to the reagents to start the reaction, which is less likely to damage the cells, he said. The patent, US Patent No. 6,872,538, is entitled “High-throughput screening diagnostic and/or dosage method of an agonist and/or an antagonist for a calcium-coupled receptor.”
The new patent — which has already been issued in Europe and is pending in Japan and Canada — complements the company’s existing patent portfolio covering the aequorin protein and its expression in cell lines for cellular assays.
Although the most recent patent was awarded directly to Euroscreen, the company licensed its prior IP — five US patents and two European patents, according to the company’s web site — exclusively from the University of Georgia Research Foundation. Those patents will expire sometime in 2012, according to Gray.
Euroscreen, founded in 1994 as a spin-off from the Free University of Brussels, specializes in technology around G-protein coupled receptor assays. The company sells a variety of catalog cell lines and membranes expressing GPCRs, many of them also expressing the aequorin protein. It also provides assay procedures for radioactive, fluorescent, and luminescent assays.
Moreover, the company licenses the aequorin technology to biotechnology and pharmaceutical companies for their internal use. Euroscreen has licensed the technology to more than 30 such companies to date, among them Merck, Amgen, Bristol-Myers Squibb, Bayer, Cephalon, UCB, and Solvay.
Euroscreen also provides custom screening services, even though the company is “not a major player there” compared to competitors like Cerep of France, Pamlab, or Novascreen Biosciences, according to Gray.
Besides products and services, the company, which has 75 employees in total, 50 of them working in research and development, also has an evolving drug-discovery arm, which is engaged in finding new targets and developing drug leads. “Right now, Euroscreen is really half and half,” Gray said.
As a reagent company with such a narrow focus, Euroscreen said that its partnerships with instrument providers have been most important. “When you have a small company like ours … we recognize that we are never going to sell very much unless we work through the instrument suppliers,” Gray said.
These companies include CyBio, Hamamatsu, PerkinElmer, Molecular Devices, and Applied Biosystems. “You can practically name any company out there, and we have either worked with them or are actively working with them in order to provide our reagents,” Gray added.
In these partnerships, Euroscreen has been developing applications of its assays for luminescence readers. Euroscreen’s facility also currently serves as a customer demo site for CyBio’s CyBi-Lumax and Hamamatsu’s FDSS, and will add additional instruments later this year.
“That’s good business for us, and then we get a chance to use the instruments for internal purposes, too,” Gray said.
Gray also said that he was unsure which additional instruments the company would be adding, but said that Euroscreen is currently providing aequorin cell lines to PerkinElmer and MDCC for evaluation on their respective luminescence readers.
Internally, Euroscreen also uses Applied Biosystems’ FMAT 8100 high-throughput screening system, which ABI discontinued two years ago.
Coincidentally, one of Euroscreen’s demo site companies, CyBio, recently struck a deal with another company, Axxam, to develop flash luminescence-based cellular assays using Axxam’s Photina photoprotein (see Inside Bioassays, 1/15/2005), a possible competitor to the well-established aequorin.
However, Gray does not see Axxam, which claims Photina to be brighter and stable than aequorin, as a significant competitor yet, although he did not say why.
Rather, what has been the most significant competition for aequorin-based calcium-dependent GPCR assays, he said, are fluorescent-based assays, most notably those that are run on Molecular Devices’ FLIPR platform. “That is certainly far and away the predominant method for this reaction to be detected,” Gray said.
However, over the past 10 years, luminescence-based detection has gained a stronger foothold because of its ease of use and some advantages in terms of signal-to-noise ratio. Few instrument makers, however, provide platforms that allow the automation of luminescent detection.
Gray said that the most important automated luminescent detection systems are “home-made” devices, followed by Hamamatsu’s FDSS, CyBio’s Lumax, and soon PerkinElmer’s LumiTrak, which he said is not yet officially on the market. PerkinElmer first introduced the system at a conference in 2003. Calls to the company seeking comment on the status of the new system were not returned in time for this publication.
“It’s the penetration of those instruments that really limits chemiluminescent detection at this point,” Gray said. Euroscreen, he added, has worked with MDCC to develop application notes for the use of aequorin cell lines on both FLIPR 3 and FLIPR Tetra.
Molecular Devices clearly sees the importance of adapting luminescent assays to its FLIPR line of instruments, as it has also been working with Axxam to test Photina on FLIPR.
Interestingly, although Euroscreen has worked with PerkinElmer to develop applications in the past, it also sees PE as its number-one competitor for GPCR-related reagents. PerkinElmer assumed this status after it swallowed two of Euroscreen’s competitors, BioSignal and Receptor Biology, several years ago through direct or indirect acquisitions.
GE Healthcare, in an attempt to keep up with PerkinElmer in the GPCR reagent area, struck a deal with Euroscreen last fall, under which Euroscreen provides GE with a full product line of receptor membrane preparations, which it then sells under its own label.