Coformulations containing two therapeutic monoclonal antibodies
(mAbs) could offer various benefits like enhanced therapeutic efficacy
and better patient compliance. However, there are very few published
studies on coformulations and binary mixtures of mAbs. It remains
unclear to what extent mAbs with different physicochemical properties
can be combined in solution without detrimental effects on protein
stability. Here, we present a study including six model mAbs of
the IgG1 subclass that are commercially available. In silico and biophysical
characterization shows that the proteins have different physicochemical
properties. Thus, their combinations represent various scenarios for
coformulation development. We prepared all possible binary mixtures
of the six mAbs and determined several biophysical parameters
that are assessed during early-stage protein drug product development.
The measured biophysical parameters are indicative of the conformational
protein stability (inflection points of the thermal protein unfolding
transitions) and the colloidal protein stability (aggregation onset
temperatures and interaction parameter k
D from dynamic light scattering). Remarkably, all 15 binary mAb mixtures
do not exhibit biophysical parameters that indicate inferior conformational
or colloidal stability compared to the least stable mAb in the mixture.
Our findings suggest that the coformulation of some therapeutic monoclonal
antibodies of the IgG1 subclass could be possible in a straightforward
way as severe detrimental effects on the stability of these proteins
in binary mixtures were not observed.
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