Generating therapeutic monoclonal antibodies to complex multi-spanning membrane targets: Overcoming the antigen challenge and enabling discovery strategies

•G protein-coupled receptors, ion channels and transporters, are important targets for drug discovery.•Monoclonal antibodies and related molecules may selectively target these integral membrane proteins.•Isolation of antibodies which modulate the function of these targets has proved challenging.•Novel antigen formats and antibody isolation strategies are leading to functional monoclonal antibodies.•Antibody discovery strategies with a focus on membrane protein antigen formats are reviewed.