Qiang Chen

US Patent:

20100021477, Jan 28, 2010

Filed:

Aug 25, 2009

Appl. No.:

12/546850

Inventors:

Ping Tsui - Berwyn PA, US
Lei Shi - Radnor PA, US
Jin Lu - Radnor PA, US
John Wheeler - Radnor PA, US
Brian Whitaker - Radnor PA, US
Lionella Borozdina-Birch - San Diego CA, US
Juan C. Almagro - Radnor PA, US
Bernard Amegadzie - Radnor PA, US
Mark Tornetta - Radnor PA, US
Ramachandra Reddy - Radnor PA, US
David M. Knight - Radnor PA, US
Jinquan Luo - Radnor PA, US
Raymond W. Sweet - Radnor PA, US
Qiang Chen - San Diego CA, US

International Classification:

A61K 39/40
C12N 15/63
C12N 1/21
C07K 14/195
C07K 16/12
C40B 40/02
C40B 30/04

US Classification:

4241641, 4353201, 4352523, 530350, 5303871, 506 14, 506 9

Abstract:

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.