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APT, Atreus Site-Specifically Label Annexin V, Developing In Vivo Imaging Biomarker

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Advanced Proteome Therapeutics and Atreus Pharmaceuticals have successfully site-specifically modified annexin V using a proprietary chemical approach, APT said this week.

As a result, various chemical entities can now be attached to the protein and thus enable the development of commercial products. The first such product currently under development is a conjugate of 1,4,7-traizacyclononane-1,4,7-triacetic acid, or NOTA, and recombinant human annexin V.

APT, based in Vancouver, BC, and Atreus, based in Ottowa, Ontario, are developing the NOTA-annexin V conjugate as an in vivo imaging biomarker to help evaluate how individuals patients respond to therapies for anti-inflammatory diseases and cancer.

Annexin V is a cellular protein. While its function is unknown, it is thought to play a role in inhibiting blood coagulation. According to a statement from APT, the protein has been the object of "intense efforts" to develop in vivo molecular imaging agents because of its ability to bind to cells undergoing apoptosis and necrosis.

Earlier studies with non-site-specific protein modification have demonstrated the potential of annexin imaging to detect early rheumatoid arthritis, early response in Crohn's disease to anti-cytokine therapy, myocardial damage in acute myocardial infarction, and early response in tumors to oncology therapies, the company added.

The ability to site-specifically label human recombinant annexin V provides a platform for the generation of "numerous bioimaging candidates," said APT. The bioimages would be used initially for diagnostic and eventually for therapeutic ends.

Allen Krantz, CEO of APT, told ProteoMonitor "This is an important initiative because it has a lot of commercial potential starting with kits that can be made and sold to researchers going through diagnostics."

APT’s technology consists of ensembles of proprietary molecules and novel assays. The molecules in the ensembles are of different shapes attached to a constant reactive component. Each ensemble is made up of molecules containing an inert affinity group and a labeling affinity.

The company last year expressed its interest in forging partnerships in order to develop the technology, called protein site-targeting, to improve the efficacy of nontoxic protein therapeutics [See PM 05/22/08].

The company estimates the protein-diagnostic and -therapeutic market will reach $50 billion by 2010.

The R&D deal with Atreus was originally reached November 2007. The initial focus was to develop protein in vivo imaging agents to view the earliest changes associated with rheumatoid arthritis.

The company also is developing protein biochips, which it has been using internally on an application by application basis. There are no current plans to make the chips commercially available, Krantz said.

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