Janssen Biotech, Inc.

Lionella Borozdina-Birch

David M Knight

Jinquan Luo

Raymond W Sweet

Juan C Almagro

John Wheeler

Ping Tsui

Mark Tornetta

Jin Lu

Brian Whitaker

Qiang Chen

Bernard Amegadzie

Lei Shi

Ramachandra Reddy

Described and claimed herein are combinatorial synthetic Fab libraries displayed on a phage pIX protein. The libraries were built on scaffolds representing the most frequently used genes in human antibodies, which were diversified to mirror the variability of natural antibodies. After selection using a diverse panel of proteins, numerous specific and high-affinity Fabs were isolated. By a process called in-line maturation the affinity of some antibodies was improved up to one hundred-fold yielding low pM binders suitable for in vivo use. This work thus demonstrates the feasibility of displaying complex Fab libraries as pIX-fusion proteins for antibody discovery and lays the foundations for studies on the structure-function relationship of antibodies.

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Lionella Borozdina-Birch