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Norway's Marine Biochemicals Eyes Wider Market for Nucleic Acid Amplification, Sample Prep Products

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By Ben Butkus

Marine Biochemicals, a small Norwegian biotech with a rapidly growing portfolio of enzymes for nucleic acid preparation and amplification, nearly doubled its staff recently as it begins to transition from a strictly B2B company to one that sells research tools directly to end users.

The company, located in the small town of Tromsø in the northernmost reaches of the country, has thus far leveraged a relationship with researchers at the University of Tromsø, who trawl the near-freezing waters of the Arctic Sea to identify and develop enzymes with unique biological properties.

Thus far, Marine Biochem's strategy has met with a modicum of success, as Siemens Healthcare Diagnostics has incorporated the company's specialized heat-labile cod uracil-DNA glycosylase, or Cod UNG, into two of its in vitro diagnostic kits; while another undisclosed international company is currently testing a shrimp-derived DNAse from the company in nucleic acid sample prep kits, Marine Biochem Managing Director Jan Buch Anderson told PCR Insider this week.

"We've been employing a B2B strategy so far, so our products have not been going straight to end users primarily because we haven't had the resources or capacity to go out and reach them," Andersen said. He noted that the firm has recently launched a new website that it hopes will help "generate inquires from end users."

Representatives from the company were seeking to achieve that goal the old-fashioned way — face-to-face networking — at Cambridge Healthtech Institute's XGen Congress, held March 15-19 in San Diego.

At the XGen Congress, Anderson and others manned an exhibition booth and facilitated roundtable discussions in an effort to familiarize attendees with its product portfolio.

Although its latest incarnation is just a year old, the company got its start in the late 1980s by developing enzymes for a variety of uses from waste products from the region's important fishing industry. One of those products was shrimp alkaline phosphatase, an enzyme for purifying PCR products prior to sequencing and genotyping that is still widely used today.

In the 1990s, Norwegian biotech firm Biotec Pharmacon purchased the assets of the nascent company and operated it as a small side business that was "visible but not very profitable" despite solid sales of the SAP enzyme, Andersen told PCR Insider.

Last year, Biotec Pharmacon spun out the company, called Biotec Marine Biochemicals, as an independent subsidiary, and Andersen was brought aboard to lead the company. And just last month, the company dropped the Biotec portion of its name and began a rebranding effort that included the launch of its website.

Still, over the last decade, Marine Biochem, in collaboration with the University of Tromsø and the Norwegian Institute for Fisheries and Aquaculture, broadened its product portfolio to include the Cod UNG and dsDNase from arctic brine shrimp.

Although the products were available as early as 2002, Andersen said that they took some time to gain recognition in the marketplace primarily because of the B2B strategy originally employed by the company.

"We have gone through meticulous scrutiny to be approved as vendors for these companies," Andersen said.

Cindy Wagner, a senior research scientist with Siemens Healthcare Diagnostics, told PCR Insider this week that when it was developing its Versant kinetic PCR-based HIV-1 RNA assay for viral load monitoring, it sought to incorporate a heat-labile enzyme in the assays but was having little success.

"We needed a heat labile [enzyme] for our assays because we run our assays at a lower temperature so we can detect all subtypes of HIV," Wagner said. "One of the big issues with HIV diagnostic tests is that because HIV has so much genomic variability, it's difficult to do a PCR assay and detect all the subtypes."

Wagner added that "just as we were ready to give up," she stumbled across Marine Biochem's Cod UNG via an internet search. "I just happened to find this company in Norway that had put this product on the market," she said. "We ordered some, it worked great, and that was the beginning of our working with them."

One of the unique properties of Marine Biochem's Cod UNG is that it is highly active in the 20 to 40° C range, but its is completely and irreversibly inactivated after a brief incubation at 50° C. Most other enzymes on the market are inactivated above 60 degrees, but reactivate below that temperature, Wagner explained.

"So you can't completely inactivate them," Wagner said. "We needed an enzyme that could be inactivated permanently at 50° C, or around the temperature at which we wanted to run our assay. Being able to run the assay at a lower temperature … decreases [its] specificity so it is more tolerant of mismatch."

Wagner said that Siemens orders the enzyme from Marine Biochem as needed to use in its HIV assay, which is currently CE Marked for IVD use in Europe. Siemens also sells the assay in Canada, South Africa, and Mexico, and is currently preparing to submit it for approval by the US Food and Drug Administration — a step that Andersen said "would be big" for Marine Biochem's business.

Siemens also uses Cod UNG in its Versant kPCR assay for HCV, which is not yet on the market. Wagner said that Marine Biochem is "just terrific to work with. They have amazing customer service and … even though they are so small, they manufacture really high-quality products, which is really unusual in this industry. It's easy to find little research-y things that you can buy, but to be able to use them in an IVD product is great."

Another of Marine Biochem's enzymes, launched earlier this year, is an improved heat-labile version of a double-strand specific DNAse, or HL-dsDNase, obtained from arctic brine shrimp, that the company has sold for several years.

This DNase has a 5,000-fold or more affinity for dsDNA over ssDNA, and as such can be used to specifically degrade dsDNA, leaving ssDNA essentially intact. The heat lability of this enzyme also means that "you can get rid of [dsDNA] during the reverse transcriptase process and first-strand synthesis," Andersen said.

He added that "three or four" undisclosed customers are already buying this product, and that a "large international corporation" is currently testing the product in its sample prep kits. Andersen declined to name the company, citing a confidentiality agreement. Coincidentally, PCR Insider reported separately this week that the University of Texas Health Science Center at Houston is currently testing cell lysis and sample prep products from Roche that incorporate an arctic brine shrimp DNAse (Q&A, this issue).

Marine Biochem's other new product is a salt active nuclease, which Andersen believes is a "first-in-class" product. This non-specific endonuclease has optimum activity at high salt concentrations of 0.5M, is more active at low temperatures and high pH, and degrades DNA over RNA in a 10:1 ratio. These features make the nuclease ideal for removing DNA from cell extracts and protein samples, and Andersen envisions it being used for proteomics applications.

In addition to its new website, the company added three employees to increase its staff to eight and has tapped into additional administrative resources from its parent company, Biotec Pharmacon.

And although Marine Biochem is still a small shop, it has a sizeable R&D resource in the University of Tromsø, with which it has an informal relationship. However, considering that the company and university are co-located in a relatively remote region, and that a large part of the university's research mission is exploring Arctic marine life, it is "common practice" for the entities to work together.

Andersen said that Marine Biochem currently sponsors some research at the university, which "is doing most of our R&D, and often times it takes the right to resulting intellectual property," Andersen said. "If we opt for an exclusive license to any IP, we typically take over the commercialization process."

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