Self-interaction Assay

The development of new drugs is a long-term, challenging task that needs to be considered in many ways. Antibody drugs have become a promising drug development option due to their high binding ability and binding specificity, long cycle of circulation and very low toxic side effects. Through long-term work, Creative Biolabs has established an advanced drug testing platform to provide technical support to researchers around the world. We can quickly assess the biophysical properties of monoclonal antibodies and identify those most likely to exhibit higher characteristics such as high solubility, low viscosity, and slow serum clearance. Detection of drug self-interaction is an important reference for assessing its hydrophobicity. Our analysis method can evaluate tens to hundreds of mAbs in parallel and requires only a small amount of (microgram) antibodies to identify early mAb candidate with low hydrophobicity and improved biophysical properties.

Self-interaction During the Early Discovery Process

Antibody drugs typically have excellent biophysical properties, including high solubility and folding stability. These properties result in the widespread use of antibodies as diagnostic reagents, which are typically formulated and stored at dilution concentrations (1 mg/mL) for several years without significant loss of activity. However, these dilution concentrations are generally too low for antibody treatment, particularly for those administered by subcutaneous delivery (the preferred route of delivery). In order to achieve typical therapeutic dosages of tens of mgs of antibody per kg of body weight, large amounts of antibody must be delivered subcutaneously in relatively small volumes, resulting in the need for concentrated antibody formulations. However, the subcutaneous delivery process of mAbs tends to be unsatisfactory due to the tendency of self-association after an increase in concentration. This phenomenon can cause the properties of the solution to be inconsistent with expectations, such as aggregation and unusually high viscosity. Therefore, the selection of mAb candidates with low self-association propensity during early antibody discovery can significantly reduce the challenges that may occur during drug development.

Measurements of mAb Self-interactions

In order to solve the problem of abnormal aggregation in antibody drug delivery, direct measurement of the solubility and viscosity of antibodies is the first method scientists think of, but high concentrations of antibodies are expensive and not suitable for use in early drug development. An attractive alternative is to measure the self-interaction of antibodies in solution, which can be achieved at lower concentrations, usually by immobilizing the antibody on various types of surfaces and then detecting it’s self-interaction by flowing antibody solution. In order to increase the sensitivity of the experiment, it is necessary to significantly increase the surface area of the interaction, which is the basis of self-interaction chromatography (SIC).

Self-interaction nanoparticle spectroscopy (SINS) is another microplate assay that has been recently developed for characterizing mAb self-interactions. The utility of this assay has been significantly improved by first coating the gold particles with mixtures of polyclonal antibodies that bind human mAbs and non-specific antibodies that do not bind mAbs. This modified form of SINS, referred to as affinity-capture self-interaction nanoparticle spectroscopy or AC-SINS, enables the amount of immobilized mAb to be varied systematically by immobilizing different ratios of capture and non-capture antibodies. This leads to a significant improvement in assay sensitivity for discriminating between different mAbs.

Creative Biolabs evaluates the stability and abnormal aggregation of drugs during in vivo delivery through the detection of drug self-interaction. This not only helps to reduce the risks and costs of subsequent drug development but also provides a way to further improve the subcutaneous delivery of therapeutic antibodies.

If you have any questions about our manufacturability assessment service, you can contact us by email or send us an inquiry to find a complete solution.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

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