Discovering and Developing Antibodies against Difficult Targets

Biologics are the fastest growing class of pharmaceuticals, with hundreds of monoclonal antibodies (MAbs) currently being developed and over thirty MAbs approved for the treatment of conditions ranging from cancer to autoimmune and inflammatory diseases. The most popular molecular targets, however, are heavily pursued, while more difficult targets are often avoided despite their significance and therapeutic need. To enable the isolation, characterization, and engineering of MAbs against challenging membrane protein targets, Integral Molecular has developed the MPS Discovery Engine. The platform uses virus-like particles (Lipoparticles) containing concentrated membrane proteins to isolate conformationally-sensitive, inhibitory MAbs against native protein targets. MAbs are characterized for specificity, binding kinetics, and functional efficacy, enabling the identification of promising lead candidates. Hundreds of epitopes for MAbs against complex membrane proteins have been determined. MAbs are optimized as needed using Shotgun Mutagenesis, a comprehensive mutagenesis platform for structurally complex human proteins, to affinity mature or humanize MAbs for preclinical development. MPS has been used to derive MAbs against integral membrane proteins that have been extremely challenging, including therapeutically-relevant GPCRs, ion channels, transporters, and viral Envelope proteins.