Generating antibodies against G Protein-Coupled Receptors and ion channels is challenging. In fact, only one GPCR-targeting therapeutic antibody has been approved in the entire world. Over the years a number of antibody discovery techniques have been explored, including screening of recombinant antibody libraries with wild type proteins, or more classical in-vivo immunizations using peptide-conjugates and genetic immunization. These approaches, as well as others involving preparations of protein detergent complexes, proteoliposomes or nanoparticles, typically fail to generate specific, high-affinity or functional antibodies since the presented antigens lack molecular homogeneity, conformational relevance, as well as properly accessible extra-cellular domains.
Abilia Bio is able to generate EMPs™, which not only have increased Tms (melting temperatures), but also are stable when formulated in buffers compatible with typical immunization protocols and library screenings. Our selection method allows for identification of variants in apo form (unbound), as well as variants stabilized in agonist, or antagonist-bound conformations, thereby maximizing the probability of discovering antibodies that not only bind, but also have agonistic or antagonistic functions. Lastly, EMPs™ do not necessitate the use of loop fusions or loop deletions.