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Dec 1, 2010 (Vol. 30, No. 21)

Adoption of Label-Free Technologies Surges

Methodologies Like SPR and ITC Are Saving Researchers Time and Money

  • Click Image To Enlarge +
    Molecular model of coagulation factor X binding to adenovirus type 5 (based on cryoelectron microscopy data): Adenovirus is in blue and factor X in purple. [GE Healthcare]

    There is an explosion of biophysical methods being used in the discovery phase of biotherapeutics, according to Fredrik Sundberg, director of strategic market development at GE Healthcare.

    “Label-free technologies including surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC) are becoming more widespread. This is because scientists are more aware of how to interpret the data from these techniques, and are using them for designing better biological drugs and vaccines. Also, these are real-time assays, which can offer significant time savings,” Sundberg explained at the recent “Developments in Protein Interaction Analysis” (DiPIA) meeting in Barcelona.

    Noxxon Pharma is just one of the many companies using label-free technology for discovery and preclinical development. “Aptamers are oligonucleotides that bind and efficiently inhibit target molecules in a manner conceptually similar to antibodies,” reported Christian Maasch, Ph.D., director of biophysical analysis.

    “They are identified by an in vitro selection process. Conventional RNA or DNA aptamers are susceptible to degradation by ubiquitous nucleases. A stabilized aptamer, Eyetech’s  Macugen, has been approved by the FDA as an intravitreal injection for the treatment of age-related macular degeneration.

    “Noxxon has developed chemical entities based on mirror-image RNA oligonucleotides, which we call Spiegelmers®. These don’t occur in nature, are not metabolized, and do not hybridize with native nucleic acids.

    “We are using SPR to support lead candidate identification and preclinical development, including hit analysis, kinetic evaluation, selectivity determination, and epitope mapping to characterize their binding activities, search for potential antidrug antibodies, and detect plasma protein binding.”

    Using these applications of SPR the company has identified two lead candidates, NOX-E36 and NOX-A12, that have been tested in Phase I trials. NOX E36 (MCP 1 antagonist) is going to be developed to treat diabetic complications such as nephropathy. NOX A12 (SDF 1 antagonist) can be used to mobilize hematopoietic stem cells from bone marrow and to treat hematological and solid tumors.

    “We believe the Spiegelmer technology combines the benefits of small molecule drugs and biopharmaceuticals, including the easily scalable chemical manufacturing process, the exceptional target specificity, and inhibitory potency. In preclinical, as well as clinical studies, we have confirmed that the beauty of Spiegelmers, besides their exceptional stability, is that they don’t activate the innate immune responses like conventional oligos can and are eliminated by the kidneys as intact product with a half-life of more than 40 hours. The recent progress in the clinics shows that Spiegelmers are well suited for further drug development, which is planned to be partnered at later stages.”

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