Affinity Maturation

Antibodies generated using in vitro or in vivo techniques may have desired biological activity but be deficient in other properties. Specifica has adapted the Generation 3 library platform to affinity mature antibodies from any source, guaranteeing at least 10-fold affinity increases — while simultaneously improving developability.

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- to 200-fold over the starting antibody affinity.

Low affinity is the most frequently required improvement, but Specifica can also provide optimization of developability, cross-reactivity and pH modulation.