When we undertake an antibody discovery campaign for you, our goal is to generate as many different target-specific antibodies fulfilling your requirements as possible.
Using three powerful coordinating technologies, we first carry out selections from our Generation 3 phage display libraries to obtain an initial pool of antibody leads with maximum diversity. We then use yeast display to narrow this down to a diverse, high affinity fully binding population, reflecting requirements for cross-reactivity, ligand antagonism or additional specificity needs. Finally, we evaluate selection outputs with next generation sequencing and AbXtract, Specifica’s NGS analysis software.
The sequences obtained by NGS are analyzed by machine learning to group antibodies into different clusters expected to bind the same epitope. Our selected antibodies have high affinities, inherently developable biophysical properties and broad diversity, making your transition from lead to drug that much faster.
The final product can be a panel of antibodies in any format, or an extensive list of different antibody clonotype sequences you can make and test in house.
Specifica has adapted the Generation 3 library platform to affinity mature antibodies from any source. The process involves the initial creation of phase 1 libraries based on the antibody to be matured in which HCDR1/2, LCDR1/2, LCDR3, and HCDR3 if needed, are replaced with scaffold-matching CDRs from the Generation 3 platform. This is followed by yeast display, with the best outputs after sorting for improved affinity combined in a phase 2 library. As sequence liabilities are purged from the CDRs used, developability improvement occurs simultaneously with affinity maturation, which ranges from 10-200 fold over the starting antibody affinity.