Antibody Discovery: Sourcing of Monoclonal Antibody Variable Domains
William R. Strohl
Affiliation: VP, Biologics Research, Biotechnology COE, Janssen Research & Development, LLC, Pharmaceutical Companies of Johnson & Johnson, SH22-22462, 1400 Welsh & McKean Rds., PO Box 776, Spring House, PA 19477, USA.
Keywords: B cells, camelid, chicken, human, monoclonal antibodies, mouse, non-human primate, phage display, rabbit, shark,
therapeutic antibodies, transgenic mice, variable domains.
Historically, antibody variable domains for therapeutic antibodies have been sourced primarily from the mouse
IgG repertoire, and typically either chimerized or humanized. More recently, human antibodies from transgenic mice producing
human IgG, phage display libraries, and directly from human B lymphocytes have been used more broadly as
sources of antibody variable domains for therapeutic antibodies. Of the total 36 antibodies approved by major maket regulatory
agencies, the variable domain sequences of 26 originate from the mouse. Of these, four are marketed as murine antibodies
(of which one is a mouse-rat hybrid IgG antibody), six are mouse-human chimeric antibodies, and 16 are humanized.
Ten marketed antibodies have originated from human antibody genes, three isolated from phage libraries of human
antibody genes and seven from transgenic mice producing human antibodies. Five antibodies currently in clinical trials
have been sourced from camelids, as well as two from non-human primates, one from rat, and one from rabbit. Additional
sources of antibody variable domains that may soon find their way into the clinic are potential antibodies from sharks and
chickens. Finally, the various methods for retrieval of antibodies from humans, mouse and other sources, including
various display technologies and amplification directly from B cells, are described.
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