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Proteome Sciences Inks Deal with Thermo Exchanging TMT IP for Cash, Aid in SysQuant Clinical Work

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Proteome Sciences said this week that it has signed an agreement with Thermo Fisher Scientific providing access to patents related to its Tandem Mass Tags isobaric tagging reagents in exchange for cash and a no-cost lease from Thermo Fisher for mass spectrometry equipment.

The company plans to use that equipment to further develop its SysQuant assays for measuring activation of cancer signaling pathways with the ultimate goal of building clinical test for guiding personalized cancer treatment, Proteome Sciences COO Ian Pike, told ProteoMonitor.

Proteome Sciences put the value of the deal at $2.1 million, making it the largest contract the company has won to date.

The TMT portion of the agreement concerns patents covering the use of MS3 fragmentation with these reagents.

Isobaric labeling uses stable isotope tags attached to peptides of interest to enable relative or absolute quantitation of proteins via tandem mass spectrometry. Typically, digested peptides are labeled with tags that fragment during MS2 to produce signals corresponding to the amount of peptide present in a sample.

Recently, however, researchers – particularly Harvard University's Steven Gygi – have begun using MS3 level quantitation to eliminate certain precursor interference problems inherent in the isobaric tagging process (PM 10/14/2011). In July, Proteome Sciences introduced an MS3 workflow for use with its TMT reagents.

A major drawback of these MS3 approaches, however, has been that the extra cycle time required for this additional level of fragmentation significantly reduces the number of peptides researchers are able to measure in an experiment. The improved duty cycle of Thermo Fisher's new Fusion Tribrid mass spectrometer – released this week at the American Society of Mass Spectrometry annual meeting (see story this issue) – largely eliminates this problem, which perhaps explains the timing of the company's deal with Proteome Sciences to obtain access to its MS3 IP.

Sold through an exclusive license to Thermo Fisher, the TMT reagents are one of Proteome Sciences' main businesses. In 2012, the company posted £431,492 ($675,414) in sales of the reagents, more than one third of its total 2012 revenues of £1,152,967, and a 41 percent increase over the £306,659 in TMT sales it reported in 2011.

Proteome Sciences currently offers TMT reagents capable of 10-plex experiments and plans to add reagents capable of 20-plex and 30-plex experiments sometime in 2014.

More significant for the company than the TMT portion of the deal, Pike said, is the opportunity it presents for expanding and refining its SysQuant phosphoproteomic assays. These assays use mass spec and TMT to quantify protein phosphorylation levels with the aim of measuring activation of cancer signaling pathways. Currently, Proteome Sciences has assays for measuring roughly 11,000 phosphosites across more than 2,500 proteins.

Under the new agreement with Thermo Fisher, the companies will collaborate on increasing the number of phosphosites covered by the assays and improving analysis of this assay data as well as developing more targeted clinical panels measuring activation levels of specific cancer signaling pathways, Pike said.

"The concept is that the clinician takes the tumor, sends it to the lab, gets it analyzed [via SysQuant], and the profile that is given is a priority-ranked list of the most likely signaling networks driving that tumor," he said. "Then you can go within those [pathways] to individual proteins and say, 'These are the top five most increased or decreased phosphorylation events in that pathway... and we know [for instance] this one is a target for dasatinib, this one a target for trastuzumab,' and you can help the clinician make a better [treatment] decision."

In its clinical ambitions for SysQuant, Proteome Sciences is entering an area that has until now been largely the domain of immunoassay approaches, and reverse phase protein array-based methods, in particular.

Last week, for instance, researchers associated with breast cancer charity the Side-Out Foundation presented pilot study data at the American Society of Clinical Oncology's annual meeting, demonstrating the ability of phosphoproteomic cancer signaling data generated via RPPA to aid in guiding therapy in metastatic breast cancer patients (PM 6/7/2013).

Also at last week's ASCO meeting, biotech firm Theranostics Health, which was co-founded by Side-Out researchers and RPPA inventors Emanuel Petricoin and Lance Liotta, introduced a commercial phosphoproteomic assay for guiding therapy in breast cancer patients – the TheraLink HER Family Assay, a test intended as a supplement to conventional HER2 testing.

RPPA has advantages over mass spec for such work due to its greater sensitivity and ability to work with smaller sample sizes – in many cases a key requirement for clinical work. Pike acknowledged these advantages, but said that mass spec offered potential advantages, as well – specifically, its potential for greater comprehensiveness and the elimination of antibodies and the accompanying issues of non-specificity and cross-reactivity.

"We can do about 11,000 unique phosphorylation sites at the moment with the SysQuant workflow," he said. "So that means a density of signaling networks we can cover is much greater than [antibody-based methods]. That is really the power of the mass spec."

For its current SysQuant workflows, which it runs on an Orbitrap Velos, the company requires around 3 mg of protein. Pike suggested, however, that the improved sensitivity of newer mass specs would bring down that requirement. He declined to say which mass specs Proteome Sciences planned to obtain from Thermo Fisher via the new agreement, noting that the company would likely make an announcement regarding this later in the year.

The company is collaborating with a number of researchers on applying the SysQuant assays to clinical research, including King's College Hospital researcher Nigel Heaton, with whom they recently used the assays to study recurrence in 12 pancreatic cancer patients, Pike said.

In that work, he said, the researchers were able with SysQuant to build phosphoproteomic profiles identifying five out of six patients who suffered recurrence and five out of six who did not.

Proteome Sciences also has collaborations surrounding SysQuant underway with one unnamed pharmaceutical firm and is in discussion with several others, Pike said.

The company currently offers SysQuant commercially as a contract research service, he said, adding that he thought it would be possible to commercialize it as a clinical assay within the next several years.

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