Biophysical Characterisation of Therapeutic Monoclonal Antibodies – Stability and Forced Degradation Studies

Dynamic interactions involving biomolecules drive and regulate all biological processes, making interaction analysis a key area of academic and industrial research and development. Specificity of binding interactions of biomolecules, and thus their function, is tightly linked to their Higher Order Structure(HOS) and stability. Among biomolecules, antibodies have naturally evolved as a class of proteins with unique ability to bind selectively and tightly to diverse targets. This ability has positioned antibodies as one of the key classes of the biotherapeutics. The integrity of the HOS of an antibody is critical to its binding specificity to antigens and Fc-receptors on immune cells, which are essential for initiating immune responses such as antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis(ADCP). Alterations in HOS can impair these interactions, reducing the therapeutic efficacy of the antibody.

Robust product characterisation throughout all phases of antibody development is required to secure control over its structure and function. Intrinsic complexity of the structural organisation of antibodies poses significant analytical challenges and require domain resolution. By employing biophysical techniques, researchers can probe various aspects of antibody behaviour, from assessing conformational integrity and aggregation propensity to determining binding kinetics and elucidating post-translational modifications.

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