Thermo Fisher Scientific and Intrinsic Bioprobes announced this week an agreement to develop and market a method for the detection of parathyroid hormone, or PTH, based on IBI's mass spectrometric immunoassay platform.
The collaboration aims to turn IBI's technology, called MSIA, from a tool it has offered exclusively for contract-research into a turnkey product available to clinical research laboratories around the world, IBI founder and President Randall Nelson told ProteoMonitor.
"We've been making a living off of doing MSIA for the last 15 years," he said. "We've just been doing it in a contract research mode pretty much under the radar. Now it's time to see if we can move this stuff out into the clinic."
MSIA relies on a patented pipette immunoenrichment technology that uses a high-throughput, high-binding-capacity microcolumn activated with antibodies to isolate low-abundance proteins in complex samples. Researchers analyze the isolated proteins via single reaction-monitoring mass spec, which enables them to quantitate protein variants.
In the case of PTH, MSIA enabled researchers, including Nelson and several Thermo Fischer scientists, to identify a number of new protein variants associated with the hormone that could be useful in developing biomarkers for various skeletal and endocrine diseases. The results of their work were published in a paper in the February 2010 issue of Clinical Chemistry.
"When we applied mass spec immunoassay to it, we found that PTH is several different variants. People knew that, but they didn't know how broad it was," Nelson said. "There are about 10 different versions of it in your body. And you can capture information on those 10 versions, or however many there are, using mass spectrometry."
Certain variants "will tell you something slightly different about the disease state you're in," he added."'So you're really looking for these slight idiosyncrasies in these hormones [and asking] 'Did it truncate, did it phosphorylate?"
Mary Lopez, director of Thermo Fishers' BRIMS Center, told ProteoMonitor that "most clinically relevant analytes are present in more than one form, and this is extremely important for the disease progression. None of the traditional approaches using ELISA can show this."
"They just don't have the specificity," she said. "Coupling traditional [immunocapture approaches] with mass-spec detection gives the added level of specificity where we can now look at these protein variants "
The decision to transform MSIA technology from a contract research tool into an off-the-shelf commercial platform stems from proteomics' ongoing shift in focus from discovery to clinical applications, Nelson suggested.
"What's happened is that proteomics has driven to the point where it's gone beyond a "discovery entity," he said. "It's produced discovery data that somebody now needs to do something with."
According to IBI CEO Dobrin Nedelkov, "in the last few years the proteomics community has come to terms [with the notion] that trying to determine how many proteins are in the human blood or plasma or serum is a pointless approach."
So researchers in the community are "focusing more on individual proteins, studying them one at a time with targeted proteomics approaches," Nedelkov told ProteoMonitor. "And when that became the modus operandi in the proteomics community, our approach, among others, was brought into focus.
According to Nelson, "suddenly the market has opened up for us," and the partnership with Thermo is meant to capture it.
"IBI has been working for 15 years on these mass-spec immunoassays, always with the intent to take them into the clinic," he said. "But we're just a small company, and to move things to a higher level we have to start working with bigger companies."
The deal with Thermo "would be the first example of that," Nelson added. "To do it right you've really got to industrialize it, standardize it. You're really talking about big industry here."
Nedelkov agreed, saying IBI has "a lot of parties interested in getting access to the technology. And we had limited resources to address this interest. So we said, 'OK, we need to partner with somebody who has access and instruments, workflow, sample prep and everything, to help us get the technology to everybody who's interested in it.'"
Thermo Fisher plans to roll out a beta version of the platform sometime this year and to begin commercial sales shortly thereafter, according to Lopez.
'PTH is a Start'
Terms of the alliance call for Thermo Fisher to license IBI's KTH assays, which will initially be run on Thermo's TSQ Vantage triple-stage quadrupole machines and its Exactive benchtop machines. The technology is also compatible with Thermo's Orbitrap machines for discovery-based workflows, Lopez said.
Going forward, IBI plans to develop assays for an additional five to 10 clinically relevant analytes, Nedelkov said.
"PTH is a start, and we have a few more targets in mind that we're going to start working on in the next month or so," he said. Nedelkov noted that IBI was focusing not on biomarker discovery but on applying the MSIA platform to established targets that "have already been proposed to be biomarkers or have been accepted and FDA approved."
The companies' current deal covers only the PTH assay, but Nedelkov said IBI and Thermo Fisher plan to discuss future assays and eventually to work on them "jointly". IBI is not currently developing the MSIA platform for use with any other mass spec, but Nelson said the company would be open to working on MSIA assays with other instrument makers in the future.
Thermo Fisher is working to develop the system with input from a small group of clinical labs, Lopez said.