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With New GPCR Patent in Hand, Odyssey Thera Looks at High-Content Receptor Signaling


Odyssey Thera said this week that the US Patent and Trademark Office has granted it a patent covering an assay for GPCR and fluorescence-based protein complex analysis.

In addition, Odyssey, which has traditionally used its assay technology in R&D alliances with pharmas and biotechs, is “currently investigating strategies” to make it available to a wider customer base on a fee-for-service basis.

The technology expands Odyssey’s position in complex-based assays, and strengthens its IP coverage in these two areas, an Odyssey official told CBA News this week.

US Patent 7,488,583, “Fragment Complementation Assays for G Protein-Coupled Receptors and Their Signaling Pathways,” adds “a lot more depth to the concept covered by Odyssey’s core IP” portfolio, which is centered around measuring the existence and location of protein complexes that are “simply lacking in other profiling strategies,” according to Odyssey Thera CEO John Westwick.

The new patent covers canonical and non-canonical GPCRs that signal in the Wnt and hedgehog pathways. “In the patent, we go to some length in describing downstream events in the GPCR pathway, so its not just GPCRs and β-arrestin here,” according to Westwick.

It also covers other proteins that are known to interact with GPCRs, but prior to the patent being issued, assays did not exist for looking at these events, said Westwick.

“For example, Odyssey now has assays to look at protein kinases such as protein kinase C and [GPCR] kinase that are known to interact with, and have profound effects on, GPCR activity,” he said.

The patent also covers the ubiquitination of proteins in GPCR signaling pathways. “We discuss those events in the patent, and we have created assays that are covered in the new patent … to look directly at the ubiquitination of proteins in GPCR pathways,” said Westwick.

According to Westwick, the protected assays are compatible with “any instrument that allows you to discriminate at the subcellular level.” He said Odyssey has tested them on the PerkinElmer Opera, the MDS IsoCyte, the TTP Labtech Acumen Explorer, and the MDS Discovery-1 platforms.

They will also support primary ultra high-throughput screening in high-density formats — “say, 1,536 [wells] or perhaps beyond that,” Westwick said. “We have demonstrated that they will work in the 1,536-well formats.”

“As long as you are capturing that subcellular localization, you will be able to image these sorts of assays,” he said. And with platforms designed to scan whole wells, the throughput is going to be “extremely high and compatible with screening large chemical files.”

In the future, Odyssey plans to “accelerate our discussions with companies that are really interested in improving GPCR-targeted drug development,” said Westwick, without elaborating. “The ability to better understand the biology of GPCRs is not lost on any company working in this area, and this capability has attracted a lot of interest.”

He also said that he expects the new patent to put Odyssey “even more on the radar screen” of companies working in this space, and hinted “there would be some significant announcements from Odyssey on the R&D alliance front in the first half of 2009.”

In an e-mail this week to CBA News, Westwick said that biotechs and pharmas are taking a widespread interest in GPCR screening, and “the trend is going rapidly to contextual assays.”

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In particular, the role of GPCR dimers and heterodimers is now recognized as essential, and “the technology described in our patent is the only feasible way to screen these events at the present time,” Westwick wrote. He also said that he expects “novel therapeutics to emerge from these strategies.”

According to Westwick, Oddesey is “currently investigating strategies for bringing [its assay] technology to the broad audience that wants it, while maintaining our internal focus on drug development and deep R&D alliances.”

The company’s business model was not originally designed to market kits or offer fee-for-service-style screening and profiling, and it “now realize[s] that the demand for our technology outstrips our ability to deliver to the wide range of researchers seeking access” to it, he added.

Assay Dynamics

Most of the dynamics of GPCR signaling events that the assay is meant to study “require high-content analysis to capture them,” said Westwick. If a researcher is looking at GPCR dimers, heterodimers, or complexes with β-arrestin, for example, all of their dynamics are associated with the subcellular translocation of those complexes.

However, GPCRs’ interaction with one another or with accessory proteins like β-arrestin are “not very dynamic, or, in some cases, not dynamic at all,” said Westwick.

And since GPCR complexes, which are pre-existing, move around radically in the cell following agonist stimulation, if their movement is not captured on a high-content instrument or an automated microscope, it cannot be seen.

Other “currently available methods” can only measure the existence of these protein complexes, but not their subcellular localization, Westwick said. By comparison, the technology covered by Odyssey’s new patent can be used to visualize this localization.

“Probably the most important application of the patented technology is the fluorescence-based assays based on these GPCR complexes,” Westwick said. “So I think the fact that we protected that is really the key value here [for Odyssey].”

The patented technology allows Odyssey to continue its R&D alliances with pharmaceutical and biotech companies that are “focused on and want to go deeper into the GPCR field, or essentially improve drugs targeting GPCRs,” said Westwick. He added that it is important to be able to target these dimeric complexes, which is how GPCRs work in organisms.

For example, GPCRs are important in Odyssey’s core areas of oncology and neuroscience, said Westwick. For instance, it is known that the pathology of, and potential therapy for, Parkinson’s or Alzheimer’s disease will require researchers to understand dopamine signaling at a more sophisticated level than they currently do.

“So companies working in these fields will be interested in these GPCR capabilities,” he said.

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