Rationally Engineered human antibody libraries and their use for the selection of therapeutic monoclonal antibodies

• Library design and construction in scFv and Fab formats for improved developability and functional
  diversity. Based on a single framework, we have developed several generations of antibody libraries. In its last design, the library is essentially devoid of potential post-translational modification sites and gives rise to highly expressed antibody molecules. The synthetic design also facilitates the selection pathway in particular when using next generation sequencing to analyze antibody repertoires.  
• We will describe some selections with the available libraries like pH-dependent antibodies for improved cancer targeting. A new display system to couple phage display in Fab format with IgG selection in mammalian cells. We have developed a new phage display system in E coli that allows a direct reformatting of the antibody fragments as full-length IgG in mammalian cells. The system permits an initial screening by phage display for the first panning steps followed by a second selection on mammalian
  cell by surface display in a IgG format, and a test of the full-length glycosylated antibodies produced in the supernatant. By coupling phage display and mammalian cell expression, the system associates the better of both worlds, that are the use of very large libraries of antibodies with direct functional characterization in the final therapeutic human IgG format.  

Pierre Martineau, Team leader, IRCM & Scientific Advisor, Mabqi