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Will New IP for GPCR Screening Assays Lead to Windfall for Norak Biosciences?

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Norak Biosciences last week strengthened its cell-based assay intellectual property portfolio when it was issued a new US patent for a broad suite of assays used to screen drugs against G-protein coupled receptors.

GPCRs are one of the most widely studied cellular therapeutic targets, as more than 30 percent of the approximately 500 drugs on the market modulate GPCR activity, according to the biotechnology and drug-development company. Agonists and antagonists of GPCRs find therapeutic benefit in conditions such as pain, asthma, peptic ulcers, and hypertension, Norak said.

The increased IP coverage gives Norak a stronger position in a growing marketplace in which it already has a significant presence. According to the company, the 2002 market opportunity for GPCR assays in drug discovery was estimated at $260 million, and was growing at an annual rate of 15 percent.

The new patent “more broadly protects” the underlying basis of Norak’s commercially available Transfluor assay, which was developed by Duke University researchers Marc Caron, Robert Lefkowitz, and Larry Barak. All three subsequently played a role in founding Research Triangle Park, NC-based Norak, which now holds an exclusive worldwide license to the technology.

The basis of Transfluor, Norak’s flagship assay, is the intracellular molecule arrestin, which when bounded to GPCRs triggers its deactivation following extracellular binding of a drug molecule. Consequently, by attaching a reporter molecule to arrestin, researchers can monitor its movement in the cell as an indirect indicator of what’s happening to the GPCR molecule.

According to Carson Loomis, senior vice president of research at Norak, the company already had two US patents, numbers 5,891,646 and 6,110,693, which cover “arrestin-based methods to detect, assay and screen GPCR activity, identify GPCR ligands, and monitor steps in GPCR regulation.”

The newly issued patent, number 6,770,449, “more broadly protects” the Transfluor assays, the company said in a statement. According to Loomis, this means the patent claims “go beyond the Transfluor technology use to cover all other uses of labeled arrestins. Assays that utilize arrestins in the US or Europe, whether Transfluor or others, will require a license from Norak,” he said.

Loomis added that this is applicable to any type of label that is attached to an arrestin molecule, but specifically GFP, B-galactosidase or luciferase — three of the most widely used reporter molecules in drug screening, and in cell biology in general.

With its existing patent estate, Norak has licensing agreements with Merck, Hoffman LaRoche, Eli Lilly, and Lundbeck as major customers, according to Loomis. Each of these deals is on a limited basis through either flat-out technology licensing or screening collaborations in which Norak screens GPCRs against the customer’s or Norak’s own small-molecule collection, the company said. Most companies with in-house screening programs license Transfluor on a “per-receptor” basis, Norak said.

According to a company executive summary provided to Inside Bioassays, Norak’s business strategy is to make Transfluor the “industry standard” for GPCR-based high-content assays and drug discovery.

Loomis said Norak’s biggest competitors here are PerkinElmer and GE Healthcare, adding, however, that “a lot of these [assays] are off patent now.”

Loomis said that although Norak doesn’t endorse the use of any specific screening instrumentation, the company has partnered with almost all of the major producers of these kinds of instruments to validate the assay on their platforms.

These instruments include: GE Healthcare’s IN Cell Analyzer; TTP Labtech’s Acumen Explorer; Cellomics’ ArrayScan; Molecular Devices’ Discovery-I and ImageExpress (formerly an Axon instrument); Evotec’s Opera; Beckman Coulter’s Cell Lab IC 100; CompuCyte’s ICyte; and BD Biosciences’ Pathway HT (formerly an Atto Biosceinces instrument).

The increased market presence of Transfluor would also be a financial windfall for those who hold the IP rights to methods using specific reporter molecules — for instance, GFP and its variants, which are perhaps the most popular tools for conducting live-cell assays from the gene expression level.

“The practice of Transfluor requires the use of a GFP to prepare the beta-arrestin2 GFP construct,” Loomis said. The company has licensed, with rights to sublicense, GFPs from two different sources: Aequorea victoria from GE Healthcare Biosciences and Renilla reniformis from Prolume, he added.

The assay is Norak’s flagship technology, but the company also nurtures a fledgling drug-discovery business. Norak said it has cloned approximately 50 GPCRs and developed approximately 70 stable cell lines for use in its own development activities and its licensed partners, Loomis said.

Approximately 70 percent of Norak’s business is focused on three discovery and development programs designed to leverage its expertise in GPCR research, Loomis said. Two use Transfluor as a tool to investigate desensitization targets, “which have been difficult to explore with existing technologies,” he added.

Norak said it currently has a screening library of approximately 900,000 diverse, drug-like, small-molecule compounds. And like medicinal chemistry company Scynexis, also based in Research Triangle Park, Norak has begun medicinal chemistry efforts for its first compounds of interest.

Currently, Norak has six GPCR targets in various stages of screening and lead generation, but none has advanced any farther down the pipeline as yet.

— BB

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