A key challenge in developing therapeutic monoclonal antibodies (mAbs) is their complex self-association behavior at high concentrations (>50 mg/mL). Unfortunately, the low purities, small quantities and large numbers of mAb candidates available during antibody discovery are incompatible with conventional methods of measuring mAb self-association. We are developing a method (affinity-capture self-interaction nanoparticle spectroscopy, AC-SINS) for identifying mAbs with low self-association propensity that is robust at extremely low antibody concentrations (<0.05 mg/mL) and in the presence of contaminants. Gold nanoparticles are conjugated with polyclonal antibodies specific for human mAbs, and these conjugates are used to capture mAbs from dilute solutions. We find that the interparticle distance-dependent plasmon wavelength of the gold conjugates redshifts in a manner that is well correlated with light scattering measurements conducted at orders of magnitude higher antibody concentrations. We are currently using AC-SINS for identifying mAb candidates with high solubility during antibody discovery as well as for improving mAb formulation during antibody development.

Optimizing monoclonal antibody selection and formulation using self-interaction nanoparticle spectroscopy

247th National Meeting (2014)

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