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Singulex Receives US Patent for Cardiovascular Biomarker Assay, Begins Planning FDA Submission

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By Adam Bonislawski

Alameda, Calif.-based biotech firm Singulex this week announced it has been granted a US patent related to a cardiovascular disease biomarker assay using its Erenna single-molecule immunoassay platform.

The patent follows on one the company received last year for the Erenna platform itself, and comes as it begins efforts to develop the assay as a clinical diagnostic that it hopes to submit for US Food and Drug Administration approval within the next two years.

The Erenna platform uses a capillary flow system to enable counting of single molecules in immunoassays. According to CEO Philippe Goix, the technology can quantitate target proteins with sensitivity one to two orders of magnitude greater than a standard ELISA. That, he noted, allows researchers to quantify known protein biomarkers at previously undetectable levels – potentially opening up new uses for established markers.

US Patent No. 7,572,640, awarded in August 2009, covers the flow system method used in the Erenna platform to achieve single-molecule counting. Singulex's second patent, US No. 7,838,250, awarded last month, covers the measurement of the protein cardiac troponin-I at low-abundance concentrations – the key to the cardiovascular disease diagnostic the company is developing.

Troponin-I is a well known biomarker for cardiac tissue damage, often used in acute settings to determine whether a patient has had a heart attack. It has been less useful for long-term monitoring purposes, however, because of the difficulty in measuring it at low enough concentrations to establish a baseline for normal subjects.

This, Goix told ProteoMonitor, is where Singulex hopes to apply the Erenna technology.

"If you can pick up troponin-I [in a patient], you can rule them in [as having suffered heart damage], but it's very difficult to rule anyone out, because to rule them out you have to measure [troponin-I] at normal levels," he said. "With our technology we can measure the concentration of [troponin-I] at very low levels, and now we can use that information to really monitor people and the risk that they will develop cardiovascular disease."

Conventional ELISAs can quantify troponin-I at concentrations around 30 to 40 picograms per mL, Goix said. The Erenna platform, on the other hand, measures the protein in a range of approximately 1 to 10 picograms per mL.

Equally important for cardiovascular monitoring purposes, he said, is the platform's resolution.

"Say a person measures [troponin-I levels] of 2 picograms. Normally it stays at that level give or take 50 percent. Now let's say you measure it at 5 picograms. That's 250 percent higher – so that's big," he said. "We have a technology that can measure not only 2 picograms, but that can measure [changes from] 2 picograms to 5 picograms to 10 picograms very accurately, and it turns out that there is a lot of clinical utility to that."

Singulex is not alone in the cardiovascular biomarker space. This week a study published in the European Journal of Heart Failure demonstrated that the Verisens troponin-I assay from molecular diagnostics firm Nanosphere was able to stratify patients at risk of heart failure. Other companies like BG Medicine (PM 12/03/2010) and Insilicos (PM 09/24/2010) are also investigating biomarkers for cardiovascular disease.

As part of its planned FDA submission, Singulex is working on a new version of the Erenna platform for use in clinical settings, including, potentially, at the point of care. Currently, the company offers the troponin-I assay out of its CLIA-certified lab. It offers CLIA-certified assays for the proteins IL-17A, IL-6, and TNFα, as well, which are related to inflammation and cytokine pathways. Additionally it sells a variety of non-CLIA assays for use on the Erenna platform that Goix characterized as "research grade."

Singulex also works with a variety of large pharmaceutical companies, he said, including Roche, Novartis, and Pfizer. In these partnerships, the company applies its technology to the high-sensitivity quantification of biomarkers that these firms have developed as part of their drug development efforts.

"We're very complementary to, say, a mass spec company where you have, in discovery, say, 500 biomarkers you need to look at," he said. "The next level is where you have maybe 10 biomarkers and you want maybe two fully validated. You'd use our technology for that. We develop a clinical-grade answer; we're more in the diagnostic-grade development."

Bringing high-sensitivity quantification to established markers has been a trend for single-molecule detection firms. Much like Singulex's work with troponin-I, single-molecule analysis company Quanterix has used its Single Molecule Array – or SiMoA – technology to measure the established biomarker prostate specific antigen in the blood of radical prostatectomy patients at concentrations far lower than that allowed by conventional ELISA-based tests. A study using the company's technology published in the June issue of Nature Biotechnology suggested that such high-sensitivity measurements of PSA could be useful in assessing the risk of cancer recurrence (PM 06/11/2010).

In addition to cardiovascular disease, Singulex is now looking to apply its platform to autoimmune disorders, Goix said. The company is working with researchers at New York University on rheumatoid arthritis, and in September won part of a €2.2 million ($2.9 million) grant from France's Single Inter-Ministry Fund for an R&D program headed by Indicia Biotechnology in collaboration with the Hospital of Lyon, TxCell, and Novartis, to develop biomarkers for Crohn's disease on the Erenna system. It began work on the project this month.

The company is also working to develop offerings in oncology, Goix said, as well as considering assays aimed at Alzheimer's disease. In particular, the Erenna platform has had success detecting the Alzheimer's cerebrospinal fluid biomarker amyloid-beta 42 in serum, raising the possibility of a blood-based test that could obviate the need for more invasive lumbar punctures.

"We have plans to be a diagnostic player. We definitely have plans to go that route," he said. He noted, however, that right now the company is focused on building a profitable business based on its assay offerings and services work for academic and pharma partners.

Singulex is venture funded, with backing from firms JAFCO, OrbiMed Advisors, and Fisk Ventures. It closed a $19 million financing round in January 2009. Goix said it would likely raise additional funds as it worked toward commercializing the patented technologies but declined to give further details.


Have topics you'd like to see covered in ProteoMonitor? Contact the editor at abonislawski [at] genomeweb [.] com.

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