Anchored Periplasmic Expression (APEx)

A Powerful Technology for Antibody Discovery and Combinatorial Protein Library Screening

George Georgiou, Dept. of Chemical Eng., Biomedical Eng., Molecular Genetics and

Microbiology and ICMB

Brent L. Iverson, Dept. of Chemistry and Biochemistry, ICMB

APEx opportunities

Non-exclusive licensing available SRA/partnerships for in-house (UT) Ab

development Start-up opportunities for specific

therapeutic fields Commercial status:

• Non-exclusive licenses (therapeutic Ab)

• >$ 1.5 million in royalties from the pharmaceutical industry since 2004

IP status: 2 U.S. patents issued, 3 pending

The APEx platform: fields of use

Antibody discovery Identifying protein:protein interactions

(quantitative) Protein expression maturation Enzyme discovery yes, for hydrolytic

enzymes Discovery of cell internalization/organ

targeting peptides yes

The APEx platform: other features

Freedom to operate in combinatorial protein screening

Quantitative results Employs bacteria and hence technically

facile

APEx: the core technologySpheroplasting

Receptor

Harvey et al., Proc. Natl. Acad. Sci. 101:9193 (2004)

Receptor+

APEx: technology validation

Engineering of antibodies that bind to the anthrax toxin with half-lives >20 hours; proven effective for anthrax prophylaxis and therapy

Engineering of high-affinity diagnostic Ab to methamphetamine

Engineering of Ab exhibiting markedly increased expression yield

Isolation of interacting proteins from libraries => quantitative 2-hybrid screening