As the high-content cell-based screening market heats up, another publicly traded company has joined the fray.
Instrument giant PerkinElmer announced recently that it will collaborate with Danish biotechnology firm BioImage to develop cell-based assays on the PerkinElmer EnVision HTS plate reader. BioImage said that it has already developed a suite of assays called GRIP for measuring protein-protein interactions in living cells, and that those assays have been validated on the EnVision. Financial terms of the agreement were not disclosed.
For PerkinElmer, the deal represents a clear step in the direction of high-content screening for an instrument company that doesn’t yet offer truly HCS instruments. According to Dan Sutherby, a PerkinElmer spokesperson, the BioImage deal is part of an overarching strategy by the company to stake a claim in the HCS space.
“We think that pharma has been shifting more to high-content,” Sutherby said. “What we’re trying to do here, and in discussions we’re having right now with other [companies], is to strengthen the capabilities within our existing technologies.
“Pharma wants us to help them fail faster — they’re tired of flushing down millions of dollars down the drain in Phase I or Phase II clinical trials,” he added. “This is one of the ways we can do this. Let’s take a very good high-throughput screening platform … a good set of plate readers … and let’s make them smarter.”
From BioImage’s standpoint, the agreement is an opportunity to more widely introduce GRIP, a relatively new variation on its fluorescent assay technologies. Founded in 1999, BioImage has steadily built a patent portfolio centered on a core technology termed Redistribution. In a Redistribution assay, researchers take protein targets, fuse them with GFP, and follow their translocation in drug screening.
According to Len Pagliaro, vice president of business development at BioImage, about five years ago the company began developing ancillary assays based on protein-protein interaction pairs.
“There are several different strategies, but one basically uses a bait and prey, if you will, where there are two suspected interacting proteins, and you take one and anchor it in the cell,” Pagliaro said. Depending on what subcellular structure is used to anchor the protein, it forms specific localization patterns in the cell, he added. “Then you take a prey molecule and fuse it to GFP, and if it interacts, it will take that pattern in the cell.”
Typically, Pagliaro said, in small molecule screening, “you then look for molecules that interrupt that interaction.”
BioImage worked on variations of that assay for years, Pagliaro said, and just over a year ago filed a patent application for the GRIP method, “giving us a system that is much more stable and reproducible.”
“Under appropriate conditions … when you have quenching compounds in the medium, there is an apparent difference in fluorescence intensity,” he said. “Typically, there is a quenching effect, and the apparent intensity read by a high-quality plate reader is less.
“Now you go from needing a very expensive high-content platform — the GE Healthcare IN Cell Analyzer, the Evotec Opera, the [Cellomics] ArrayScan, and so forth — to a plate reader,” Pagliaro added. “Then you have a much less expensive screening platform, which of course is very desirable.”
This is where PerkinElmer comes in, as the EnVision is a relatively inexpensive, high-throughput, and intensity-based fluorescence plate reader.
“From 1998 through now, we’ve spent a lot of money on sizeable acquisitions, whether it was Packard Biosciences, or NEN Biosciences,” Sutherby said. “So we’ve got a full suite of products we’re providing to biotech or pharma customers. We believe we have a very strong, if not the top position in high-throughput screening.”
Sutherby added that the BioImage deal is “not atypical” of how other alliances might develop. “We know what our strengths are, and we try to pursue people that complement our strengths. This was in discussions for a while … more to validate the technology, and then come to an agreement on the business front. This is highly technical stuff, so there was a long period of validation.”
It doesn’t hurt that Patrick Dahlén, BioImage’s CEO, is the former president of PerkinElmer Life Sciences, and is quite familiar with the company’s instrumentation platforms.
For an entity whose instrumentation branches out into just about every biological application area, PerkinElmer’s Life Sciences division has just started its foray into high-content cellular analysis. Its UltraVIEW confocal-based live-cell imaging instrument has been available for some time, but is primarily used for multi-parameter examination of live cells on slides for basic research applications.
More recently, the company introduced ImageTrak, an epifluorescence-based imaging system that uses fiber optics, and has automated liquid handling and data analysis capabilities for performing both kinetic and end-point assays on cells in 96-, 384-, or 1536-well microplates.
In May, when PerkinElmer signed a drug screening agreement with Australian biotechnology firm Bionomics, the company told Inside Bioassays that ImageTrak is particularly well-suited for calcium and calcium flux assays, membrane potential assays, and ion channel assays. (see Inside Bioassays, 5/18/2004)
But the BioImage deal is one of PerkinElmer’s first major steps for high-throughput — if not high-content — analysis of protein-protein interactions. It is unclear whether the company is developing a single higher-end instrument for this purpose, although Sutherby said that PerkinElmer will continue to look for ways to integrate and improve its current instruments to meet needs as they arise.
“Believe me, it is a key focus of the strategy, clearly in cellular sciences, systems biology, and more of the high-content screening, which includes proteomics,” Sutherby said. “It has been for a while, and we believe it will continue to be in the future.”
From here, BioImage will continue to build upon its GFP Redistribution patent portfolio, the history of which is as convoluted as the inner workings of a cell. Currently, Pagliaro said, the company has three main families of GFP-related patents. The first is for the molecule itself — or, more specifically, the use of it in the relatively high temperatures found in mammalian cells. Invitrogen holds the rights to it now, which it acquired from Aurora and Vertex Biosciences. Columbia University also holds related intellectual property, and GE Healthcare recently cross-licensed all the related patents for what Pagliaro termed “one-stop shopping.” (see Inside Bioassays, 6/15/2004)
The second is the Redistribution assay, to which BioImage holds patents in Europe, the US, and Canada. For drug discovery purposes, Pagliaro said, this covers any assay that broadly looks at the translocation of proteins using GFP. GE Healthcare also has sublicensed these methods from BioImage.
Finally, the company continues to work on getting wider intellectual property coverage for the GRIP assays and another type of “complementation” fluorescent assay that uses fragments of fluorescent proteins to investigate protein-protein interactions. Although patents have not yet been awarded for these techniques, Pagliaro said that BioImage has filed several applications.