Protein arrays may still be on the fringe of the microarray world in terms of marketing power, but they managed to generate plenty of excitement at the annual Chips to Hits conference held last week in Boston. This week ProteoMonitor caught up with five companies that presented on various kinds of protein arrays at the meeting to see what they’ve been up to, where they’re going next, and what they make of the protein array market.
Zyomyx, which announced a deal this week with the National Eye Institute for the use of its recently released Protein Profiling Biochip System in the study of ocular disease, has gone through a “tremendous change” since the February launch of the profiling system, said Peter Wagner, Zyomyx’ chief techno-logy officer. The Hayward, Calif., company, he said, has gone from a five-year-long R&D phase to a full-fledged marketing drive.
“This is what we have been building over the last four or five years with $90 million, and now what we’re doing this year is building a commercial setting,” Wagner said, explaining that this new setting would include the “ramping up of manufacturing, sales, and support teams.”
Zyomyx’ focus, Wagner said, is on marketing its products to pharma companies that are working in the expression profiling market and “want [them] ready to use out of the box.” That suite of products will include validated traditional antibody arrays with accompanying reagents and accessories for doing quantitation studies.
The company has so far released only one content-bearing chip on the market — a human 30-cytokine array — but Wagner said that Zyomyx will now begin releasing three to four new chips a year. “The idea is to have a substantial number of chips out there within the next 24 months. We’ve already started and will intensify next year,” he said. The next chip to come out of the pipeline will be a mouse cytokine chip, set for release in the first quarter of 2004. The company also has plans to release a chip with 100 human cytokines, as well as a signal transduction array and a whole “information suite” of chips with functional subsets, such as a growth factor chip (see PM 4-7-03).
While Zyomyx is launching these products at full speed, Wagner said he believed the protein array market would not take off until pharma accepts arrays as an important part of the drug discovery process. “The field is going from a process of early-stage curiosity into delivering solutions. You really only get [this] when you deliver to pharma and they start running clinical samples and realize the power of multiplexing,” he said. The lengthy, tedious, and costly process of validating even a 30-antibody array for quantitative analysis was a limiting factor, Wagner noted.
Schleicher & Schuell BioScience
Michael Harvey, vice president of R&D at S&S, said that the Keene, NH-based company would be releasing an anti-cytokine array called Fast Quant — containing nine interleukins associated with the Th1-Th2 immune response — that would allow for the quantitation of the cytokines present in a given sample. The product will launch in the first quarter of 2004, and will have as its base a nitrocellulose-coated slide called a Fast Slide, which S&S markets for both DNA and protein arrays, although Harvey said the slide was particularly valuable for protein arrays. The company has been focusing primar-ily on making the slides more quantitative and reproducible for use with all types of protein arrays.
Harvey said that a major obstacle to the growth of the protein array market was content — that is, “deciding which collection of specificities people really need so they can take advantage of multiplexing.” He said that Protometrix’ plans for proteome chips (see below) would help to solve that problem. The sheer breadth of potential applications for protein arrays, when compared with the more straightforward use for DNA arrays, was also slowing the market down, he said, because it “takes time to solve some of the problems that are associated with all the different applications.”
Markus Ehrat, CEO of Zeptosens, said that the Witterswil, Switzerland-based biochip company had just sold the first system that incorporates its recently launched reverse protein array. So-called reverse arrays, also being developed by Emanuel Petricoin at the FDA-NCI, immobilize the sample on the array — rather than immobilizing a set of antibodies, as is the case with conventional capture arrays. “The advantage is, if you’re interested in only 10 or 20 proteins to detect, but you have many samples, you can have multiplexing of sample and not of the protein. … Also, you have only one antibody so you don’t have too much problem with cross reactivity,” Ehrat said.
Ehrat also said that Zeptosens, which launched a DNA array based on a light propogation system called planar waveguide technology last summer (see BioArray News, 8-2-02), had adapted the high-sensitivity array system for proteins and had “just started” commercializing it.
According to Ehrat, the biggest difficulty in the expansion of the protein array market — in addition to the need to improve upon precision, sensitivity and reproducibility — was “convincing people that these protein microarrays really can provide good information.” This is no small task, Ehrat said, because protein scientists were used to a higher level of precision in their work than DNA scientists were, and “in multiplexing, they are afraid to lose this precision,” he said.
Protometrix, which was spun out two years ago based on work done at Michael Snyder’s lab at Yale (see PM 1-28-02, 4-7-03), this month began selling its yeast proteome chip, which contains 4,500 yeast proteins spotted in duplicate on one array, according to Hollis Kleinert, the CEO, and Paul Predki, the vice president for R&D. The Branford, Conn.-based company is in the “final stages” of a deal with a distributor that will do the majority of the marketing for the yeast array beginning in 2004, according to Predki. Shortly after the distributor begins selling the yeast chips, the company will begin releasing a series of sub-proteome chips for human proteins followed by chips for mice, rats, dogs, and other common model systems. “All of the key animal models that are used routinely in drug safety and efficacy-testing in pharma companies will be sub-proteomes or full proteomes that we will address,” Kleinert said.
Rather than attempting to build a whole proteome array for humans, Predki said that the company would build several sub-proteome arrays categorized according to function (such as an apoptosis array); localization in the body (such as a liver array); localization in the cell (such as a membrane array); or family (such as a kinase array). Predki added that the company currently has several thousand human proteins in stock, and that various sub-proteome chip possibilities are being tested in collaborations, at beta test sites, and in-house. Protometrix is also already “actively working on” custom arrays for particular clients, for which it will both draw from its current stock of human proteins as well as generate new content, according to Predki.
Also, the company “made an unexpected discovery” in the spring, Predki said, that led to current efforts to market arrays for the multiplexed measurement of enzymatic activity using proteins arranged in a similar format to the proteome arrays. These “activity arrays” are set to be commercialized soon as well, Predki said, noting that potential commercial value was in the area of drug discovery.
While acknowledging that there was still some resistance on the part of researchers to the concept of protein arrays, Predki took the unusual stance of suggesting that the expansion of the protein array market would be a faster and easier process than it was for DNA arrays. “We’re in a much easier situation, because a lot of the work has been done for us already,” Predki said. He noted that unlike Zyomyx, Protometrix is purposely marketing arrays with “open platforms:” Rather than selling a whole system for reading and analyzing the array, users could use DNA array-type scanners or other common labora-tory readers to read the protein arrays. Also, Predki said, users were now “conditioned” by DNA arrays to think about experiments on a multiplexed scale, so acceptance of the new technology would come more easily and quickly than it did for DNA arrays.
PerkinElmer — which launched an array analysis software tack-on to its ProteinArray workstation at Chips to Hits — has “active research going on in-house for the development of [content] arrays,” said Sandra Rasmussen, PerkinElmer’s business unit leader for proteomics and array systems. Rasmussen wouldn’t say when such arrays might reach the market, but said the company was working both on determining what type of content to put on the arrays — antibodies versus cellular proteins, for example — as well as how to put the content down so that it is stable and sensitive. “We have a team recognizing that protein arrays are more difficult than DNA arrays,” Rasmussen said.
PerkinElmer licensed the ProteinArray workstation, which automates the process of making an array, from NextGen Sciences in March 2002 (see PM 3-18-02). The newly launched analysis software, which will ship in the fourth quarter of this year, uses a standardization curve based on cytokine proteins to convert signal intensity data from the array into concentration-based data for quantitation analysis. PerkinElmer also recently released Piezoarray, a non-contact array spotter (see PM 5-12-03).