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September 01, 2010 (Vol. 30, No. 15)

Expression System Re-Targeted to Discovery

Pfenex System Repositioned to Support Early-Stage Research

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    Pfenex expression technology can be applied across the product-development continuum.

    Change is under way at Pfenex as the company works to expand its bacterial-based protein-expression system. Originally used to manufacture biotherapeutics, vaccines, and protein-based reagents, Pfenex had been working with companies to express a protein of interest for late-stage clinical development. Now the company is exploring how the system can be used for discovery.

    “In our initial business model, we developed a production strain and licensed it back to the client for production of clinical materials and commercial products,” explains Patrick Lucy, vp of business development at Pfenex.

    But when Bertrand Liang, M.D., Ph.D., joined Pfenex in 2009 as CEO, he scrutinized the company’s business model. A veteran of big biotech, Dr. Liang recognized that protein-expression problems are not limited to clinical development, but start back in the early drug discovery phase.

    Accordingly, Pfenex has repositioned its protein-expression technology to support early-stage challenges related to the discovery of large and small molecules. Discovery scientists want to move programs forward rapidly to increase the value of a company’s pipeline while minimizing costs. “To do this, scientists need soluble, active protein on demand,” says Lucy.

  • Agricultural Origin

    The Pfenex platform is based on a strain of Pseudomonas fluorescens, first isolated 25 years ago from a lettuce leaf by scientists at Mycogen, part of Dow AgroSciences. Mycogen used the microbe for large-scale production of insecticidal proteins for agricultural use. P. fluorescens adeptly produces large amounts of protein at low costs, according to the company.

    Dow Chemical acquired Mycogen in 1998, and its researchers enhanced the flexibility of P. fluorescens for large-scale production of industrial enzymes. During the past decade, the Pfenex team turned the strain into the Pfenex Expression Technology™ platform for protein production.

    The Pfenex Expression Technology platform assesses the performance of hundreds of host-strain plasmid combinations in a high-throughput, parallel manner to rapidly identify the best strain for high-yield expression of an active target protein. The platform includes an extensive library of expression tools and P. fluorescens host strains with phenotypes designed to enhance quality and stability of proteins expressed recombinantly.

    Prior to launching the platform, Lucy and colleagues at Dow spent several years perfecting it to manufacture large amounts of recombinant proteins efficiently and in a soluble, properly folded form. Dow launched the Pfenex Expression Technology platform in 2004 to perform strain-engineering work for pharmaceutical companies. Then in 2009, Pfenex became independent of Dow.

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