Objective

There are multiple parallels to be drawn between small molecule and antibody discovery, thus unsurprisingly they share many key techniques and methods. The discovery and characterisation of antibodies has its own set of challenges distinct from small molecules. In the initial screening stages small molecules commonly show weak binding but are produced as homogeneous, high concentration defined samples; antibodies however, are characterised in the initial stages as high affinity, heterogenous low concentration samples of imprecise definition. These differences require careful design of assays at the initial hit hunting phase. This talk will detail some of the technologies currently used at UCB for the discovery of pharmacologically active antibodies, including biophysical (SPR, ITC, Octet) and biochemical assays. The eventual function of the antibody is also a key consideration, not only during the hit ID phases, but also during hit characterisation. Like small molecules, there are a plethora of molecular mechanisms through which an antibody may exert its function (competitive, non-competitive, uncompetitive...). The high affinity of lead antibodies may lead to ligand depletion and misinterpretation of mechanistic data. Choice and design of mechanistic assays for antibodies is key to their success. The choice of specific screening cascades and assays can reveal potent, bioactive antibodies which are able to work through surprising mechanisms, often inaccessible to small molecules.