From rapidly obtaining sufficient amounts of active protein in early stage development to cost effectively producing kilogram and even metric ton quantities for commercial supply, protein expression is critical at every stage of biopharmaceutical drug development. Having a high-performance protein expression platform across all stages is invaluable for the speed and success of protein and vaccine development.
Historically, biopharmaceutical researchers and process development scientists have used
Escherichia coli
in their laboratories to generate small quantities of protein. If target expression was low or insoluble, they undertook larger-volume fermentation or performed a refolding step. If a product could not be expressed by
E. coli,
they would investigate alternative hosts (e.g., yeast, insect or mammalian cells). This iterative and linear process is both time consuming and expensive.
Dowpharma’s
Pf
ēnex expression technology platform addresses challenges of speed and cost at every phase of develo...
During the past five years, many biopharmaceuticals have found their way into clinical trials and commercial production (
1–4
). So far, about 60 million patients worldwide have benefited from these new drugs. The market for biopharmaceuticals was estimated at US$33 billion in 2004 and projected to reach US$70 billion by the end of the decade. During the period 2003–2006, regulators in Europe and the United States approved 32 biopharmaceuticals for human use, including hormones and growth factors, therapeutic enzymes, vaccines, and monoclonal antibody (MAb)-based products. An additional 1,600 biopharmaceuticals are being evaluated in clinical trials.
MAbs constitute by far the largest product category, with the number of such product candidates rising from 75 to 400 in the period of 2003–2006. The global sale of MAbs in 2006 were US$20.6 billion (
5–8
), and currently 25 are approved for the market. It is expected that many new MAbs will be approved within the coming years. As Figure 1 shows, demand is ra...
+1Since the 1980s launch of the first recombinant-DNA–sourced protein insulin, the 1990s introduction of interferons and interleukins, and the first commercial approval of MAbs around the turn of the century, the therapeutic protein market has shown a very healthy growth of 15–19% (Figure 1). Between 1980 and 2004, about 300 antibodies and 400 other recombinant proteins entered clinical trials, totaling about 750 products (
1
).
A survey of biopharmaceutical production technologies in 2005 shows that Chinese hamster ovary (CHO) cells and a murine myeloma cell line (NS0) among mammalian cells and
Escherichia coli
(
E. coli
) among microbial systems remain the tested and most commonly used workhorses, with known safety and productivity profiles and capabilities (
2
).
More than 66% of approved biopharmaceuticals are glycosylated proteins that require mammalian cell culture. Examples include monoclonal antibodies (MAbs), blood factors, anticoagulants, thrombolytics, EPO, granulocyte-macrophage colony-stimula...
+4 Mammalian cell expression systems are currently essential for production of glycosylated biopharmaceuticals such as monoclonal antibodies or molecules requiring even more complex glycan structures. Various host cell and vector systems aimed at improving expression levels and quality have been established (
1
,
2
). Development of biopharmaceutical product candidates from genes to clinical trials should be based on technology platforms that will require no major changes in the entire development chain, including manufacturing once a product candidate has successfully progressed through phase 1–2 clinical testing. The intrinsic cost structure thus is widely determined by the category of technology platform chosen very early in development.
Development time is currently considered by modern management to be of utmost importance. Antibody fragments (Fabs) represent an interesting category of potential biopharmaceuticals (
3
,
4
). About 20% of all Fabs have glycosylation sites that putatively might contribu...
+1 
