(743g) Rapid Antibody Discovery Platform for Antibody Drug Conjugates and Bispectific Antibodies

The development of novel antibody therapeutics, especially antibody-drug conjugates (ADCs) and bispecific antibodies, is often a challenging and time-consuming process. Utilizing Sutroâ??s cell-free protein synthesis (CFPS) system, we describe an antibody discovery platform for the selection, screening, and characterization of antibodies for novel drug targets in approximately four weeks. Using ribosome display technology, we can select binders from billion-member libraries and directly screen the clonal output in CFPS. Because CFPS allows the rapid expression of variants at high titers, we have the ability to screen thousands of variants for desirable antibody characteristics such as cell binding, cell internalization, binding affinity, thermostability, and epitope. Top leads can be further optimized for non-natural amino acid incorporation and drug conjugation for the generation of homogeneous ADCs. Alternatively, variants can be combined and evaluated as bispecific antibodies. Sutroâ??s antibody discovery platform enables rapid candidate generation and characterization for making the most efficacious and safe ADCs and bispecific antibodies.