Improved understanding of the thermal stability of a monoclonal antibody and its modified version by use of DLS/Raman spectroscopy

The combination of Dynamic Light Scattering (DLS) with Raman Spectroscopy provides the capability to investigate a wealth of chemical, structural, and physical parameters about biotherapeutic proteins under formulation conditions.

Here, we demonstrate that by simultaneously monitoring both the colloidal (DLS) and conformational (Raman) stability of a template monoclonal antibody (mAb) and a modified monoclonal antibody (mmAb) provides significant insights into the mechanistic effects of thermal stress on the mAb and the mmAb.

In particular, this combined DLS/Raman technique has revealed that the lower thermal stability (early oligomerization) of the mmAb compared to the template mAb, is initiated by a tertiary structural change in a tyrosine side chain residue; a mechanistic observation that could not have been revealed fully by the separate use of these techniques.