Generation of human de novo pIX phage display libraries

US9062305B2 · kind B2 · utility

Assignee

• JANSSEN BIOTECH, INC. · US

Inventors

• Ping Tsui · Gaithersburg, US
• Lei Shi · Radnor, US
• Jin Lu · Boothwyn, US
• John Wheeler · Spring House, US
• Brian Whitaker · Krugerville, US
• Lionella Borozdina-Birch · San Diego, US
• Juan Carlos Almagro · Brookline, US
• Bernard Amegadzie · Radnor, US
• Mark Tornetta · Collegeville, US
• Ramachandra Reddy · Conshohocken, US
• David Knight · Berwyn, US
• Jinquan Luo · Malvern, US
• Raymond Sweet · Via Enrico Fermi, US
• Qiang Chen · Sollentuna, SE

Key dates

• Filing date: Aug 25, 2009
• Grant date: Jun 23, 2015
• Expiry date: Aug 20, 2032

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C40B30/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

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.