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 technology Spheroplasting 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