Thursday, April 17, 2014
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Mice with directed
integration of human immunoglobulin transgenes to produce chimeric antibodies
with fully human variable domains
Transgenic mice that
produce chimeric antibodies with human variable domains could be used for
therapeutic antibody discovery. Previous development of transgenic mice with
humanized immunoglobulins was limited by size of and random integration of
human transgenes. In mouse embryonic stem cells, the entire human
immunoglobulin variable-gene repertoire was inserted into the corresponding
mouse loci using bacterial artificial chromosome-based targeting vectors. The
resulting transgenic mice had functional immune systems that, when inoculated
with human IL-6
produced antibodies with a wide range of binding affinities for the antigen.
Ongoing work includes testing in clinical studies a high-affinity anti-CD126
antibody in which the mouse constant domain has been exchanged with the human
Published online April 17, 2014
licensed to Astellas Pharma Inc.
to use the mice to discover human mAbs; partnership with Sanofi to
discover and commercialize human mAbs; Academic VelocImmune Investigators
Program established to provide academics with access to the mice
Macdonald, L.E. et al.
Proc. Natl. Acad. Sci. USA; published online
March 25, 2014;
Murphy, A.J. et al. Proc. Natl. Acad. Sci. USA; published online March
Contact: Andrew J. Murphy, Regeneron Pharmaceuticals, Inc., Tarrytown,
Contact: George D. Yancopoulos, same affiliation as above
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