Characterizing the Aggregation Propensity of an Anti-HIV-1 Bispecific Antibody in Two Different Formulation Buffers During Agitation Stress (Dataset)

Wang, Michael; Whitaker, Neal; Kumru, Ozan; Hickey, John M.; Joshi, Sangeeta B.; Volkin, David

Publication

Characterizing the Aggregation Propensity of an Anti-HIV-1 Bispecific Antibody in Two Different Formulation Buffers During Agitation Stress (Dataset)

Wang, Michael
;
Whitaker, Neal
;
Kumru, Ozan
;
Hickey, John M.
;
Joshi, Sangeeta B.
;
Volkin, David

Abstract

There is growing interest in administering bispecific, broadly neutralizing antibodies as a therapeutic strategy to control and prevent HIV-1 infection. Bispecific antibody (BsAb) candidates can be challenging to formulate as stable dosage forms since they are generally more prone to aggregation compared to widely commercialized monospecific monoclonal antibodies (mAbs). The anti-HIV-1 bispecific antibody 10E8.4/iMab is a promising BsAb candidate in clinical trials that is designed to block HIV-1 viral entry into cells. During initial formulation development, visible particles were observed upon storage under certain conditions. In this case study, we evaluated the physical stability of 10E8.4/iMab to better understand the aggregation and particle formation profiles before and after exposure to agitation stress. First, key structural attributes of the unstressed BsAb were determined including primary and higher-order structure, size, and conformational stability. Second, a combination of analytical methods was used to monitor the formation of soluble aggregates, subvisible particles, and visible particulates during agitation studies in Buffer 1 containing a salt (20 mM NaAc, 100 mM NaCl, pH 5.5) and Buffer 2 containing a sugar and a nonionic surfactant (20 mM NaAc, 6.5% sucrose, 0.02% PS80, pH 5.5 . Third, the particulates generated during agitation of 10E8.4/iMab in Buffer 1 were shown to contain structurally altered protein. It was observed that Buffer 2 not only minimized aggregation and particle formation during agitation but also increased the conformational stability of the BsAb compared to Buffer 1. The results from this case study are discussed in the context of enabling future developability and formulation studies with other aggregation-prone BsAb candidates.