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With BioHelix Acquisition, Quidel Brings Isothermal Amplification Tech in House

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With its acquisition this week of privately held molecular diagnostic developer BioHelix, clinical diagnostics firm Quidel adds to its portfolio of technologies to enable its burgeoning molecular diagnostics business.

Specifically, Quidel will bring in house BioHelix's helicase-dependent amplification, or HDA, technology, an isothermal amplification technology that Quidel was already using as part of its recently launched AmpliVue line of handheld, disposable molecular diagnostic products. The acquisition also provides Quidel with BioHelix's isothermal molecular assay development and enzyme manufacturing expertise.

In addition, Quidel officials noted that the HDA technology would benefit Savanna MDx, a benchtop sample-to-answer molecular diagnostics platform still under development at the company. Quidel is developing the system, previously named Project Wildcat, in collaboration with Northwestern University with initial applications in point-of-care HIV testing in remote and resource-poor areas of the world. Longer term, Quidel sees the platform being used for decentralized molecular testing in more developed countries (PCR Insider, 4/14/2011).

Under the terms of the acquisition, Quidel, which trades on the Nasdaq, will pay BioHelix shareholders $10 million in cash, plus additional amounts in connection with an R&D earn-out based on the completion of a designated number of assays and a commercial earn-out dependent on product sales over a defined period.

San Diego-based Quidel plans to operate BioHelix, which is headquartered in Beverly, Mass., as a wholly owned subsidiary. BioHelix CEO Huimin Kong will remain as president of the subsidiary.

BioHelix is a 2004 spinoff from New England Biolabs. In October 2009, it entered into a collaborative R&D agreement with Quidel under which the companies were to co-develop a number of handheld, disposable molecular assays using BioHelix's proprietary helicase-dependent amplification technology. The agreement called for BioHelix to develop the assays and for Quidel to manufacture, market, and sell new products developed under the agreement while retaining exclusive, worldwide commercialization rights to the products.

In October 2011, Quidel disclosed that its handheld molecular diagnostic tests would be sold under the brand name AmpliVue, and that it had restructured an existing deal with Alere for that company's lateral flow strip technology, which Quidel combines with the HDA chemistry in its AmpliVue assays (PCR Insider, 10/27/2011).

One of the major benefits of HAD technology for molecular diagnostics is that the entire amplification process can take place at a single temperature. Thus, rather than using heat to denature the DNA as in PCR assays, HDA uses a heat-stable helicase that enzymatically unravels the two complementary strands. As a result, it can be performed directly on extracted DNA and requires only one primer set.

Besides engaging in its collaboration with Quidel, BioHelix has in the past licensed the HDA technology to other molecular diagnostic developers.

For instance, in 2008 Qiagen licensed the HDA technology from BioHelix in order to combine it with its hybrid capture 2 technology for various molecular diagnostic tests, including assays for chlamydia and gonorrhea.

However, in 2011 Qiagen abandoned the isothermal amplification method in favor of real-time PCR-based technology for assays to be run on the next generation of its fully automated QIAensemble molecular testing platform (PCR Insider, 5/12/2011).

In addition, molecular diagnostics firm Great Basin has a license to the HDA technology, which it uses as part of a cartridge-based sample-to-answer molecular testing platform called the Portrait Analyzer. Great Basin received US Food and Drug Administration approval in May 2012 for its first Portrait Analyzer assay, for Clostridium difficile (PCR Insider, 5/3/2012).

Meantime, BioHelix has also been developing molecular diagnostic assays of its own using the HDA chemistry on a platform nearly identical to Quidel's. In October 2011 PCR Insider reported that BioHelix had scored a two-year grant from the National Institute of Allergy and Infectious Diseases to develop a handheld device also based on HAD and lateral flow, and to develop associated assays for infectious diseases including gonorrhea and chlamydia. As part of that project, BioHelix was working with the laboratory of Boston University's Catherine Klapperich to integrate its microfluidics and sample prep technology into the device (PCR Insider, 10/13/2011).

Around that same time, BioHelix won 510(k) approval from the FDA for its first HDA-based assay, a test to detect herpes simplex virus in genital and oral lesion specimens from symptomatic patients (PCR Insider, 10/20/2011).

BioHelix is also working under a Phase I Small Business Innovation Research grant from NIAID to develop a low-cost, rapid, quantitative test for HIV-1 that will use zip nucleic acid, or ZNA, technology to enhance the speed and sensitivity of the HDA technique (PCR Insider, 3/15/2012). And, finally, the company said in September that it was working on a low-cost, handheld, real-time fluorescence detection system called FireFly that would be capable of running quantitative HDA assays (PCR Insider, 9/6/2012).

It is unclear whether BioHelix will continue all of these initiatives as a Quidel subsidiary, or whether Quidel will take over the development and marketing of BioHelix's more mature assay products, such as the HSV test. BioHelix's Kong declined to comment, and emails and calls to Quidel were not returned.

Quidel said in a statement that acquiring BioHelix will accelerate the development of its own AmpliVue isothermal assays and lower the associated manufacturing costs for those assays, presumably because it will now own the HAD technology instead of licensing it from BioHelix. Quidel currently sells the AmpliVue C. difficile Assay, which received clearance from the US Food and Drug Administration in December of 2012 and was CE marked in March 2012 (PCR Insider, 12/20/2012 and 3/29/2012).

"With the launch of AmpliVue C. difficile, we have demonstrated customer receptivity to a hand-held, disposable molecular platform, which gives us confidence that this additional investment in BioHelix and its isothermal amplification technology is warranted," Quidel President and CEO Douglas Bryant said in a statement.

Quidel is also developing AmpliVue tests for herpes simplex virus, Bordetella pertussis, Group B Streptococcus, and trichomonas, among other targets.