Evaluation of recombinant monoclonal antibody SVmab1 binding to Na V 1.7 target sequences and block of human Na V 1.7 currents

Identification of small and large molecule pain therapeutics that target the genetically validated voltage-gated sodium channel Na 1.7 is a challenging endeavor under vigorous pursuit. The monoclonal antibody SVmab1 was recently published to bind the Na 1.7 DII voltage sensor domain and block human Na 1.7 sodium currents in heterologous cells. We produced purified SVmab1 protein based on publically available sequence information, and evaluated its activity in a battery of binding and functional assays. Herein, we report that our recombinant SVmAb1 does not bind peptide immunogen or purified Na 1.7 DII voltage sensor domain via ELISA, and does not bind Na 1.7 in live HEK293, U-2 OS, and CHO-K1 cells via FACS. Whole cell manual patch clamp electrophysiology protocols interrogating diverse Na 1.7 gating states in HEK293 cells, revealed that recombinant SVmab1 does not block Na 1.7 currents to an extent greater than observed with an isotype matched control antibody. Collectively, our results show that recombinant SVmab1 monoclonal antibody does not bind Na 1.7 target sequences or specifically inhibit Na 1.7 current.