Protein-based drugs are luxury goods, according to François Arcand, CEO, ERA Biotech (www.erabiotech.com). “Since most have the same market size as Cartier watches, I believe no health system in the world has the financial means to supply its general population with drugs made in mammalian cells. They are just too expensive to be widely prescribed,” he says.
With the average cost of being treated with Herceptin estimated at $60,000– 70,000, for example, it’s not hard to see what Arcand is driving at.
An area where many biotech and pharma companies are looking to reduce expenses is in their manufacturing. Scientists from ERA Biotech and a number of other firms addressed this issue at Cambridge Healthtech’s “Protein Expression Europe” conference in Prague last month. A whole raft of technologies is arising that promise greater yields and as a consequence reduced cost of goods.
One such system from ERA Biotech is a storage organelle technology triggered by assembler peptides of the Zera® family (originally derived from corn) that can accumulate proteins in any eukaryotic cell type.
“Express a genetic fusion of Zera and a protein of interest, and the cell will form membrane-bound structures, or StorPro organelles, containing high concentrations of proteins with the same solubility and structure as the native version,” Arcand explains.
The fact that the recombinant protein is not denatured as it would be in an inclusion body makes Zera technology appealing to manufacturers, Arcand adds.
The first advantage of using a protein accumulation system is that target proteins are encapsulated in vivo by the user’s choice of cell, Arcand explains. “This gives both yield and quality, as the protein is protected from metabolic and proteolytic activities, and the host cell is not exposed to any toxic effects of the recombinant protein. This encapsulation also enables production of difficult-to-express proteins.”
The second advantage is much simpler purification strategies. Since the organelles are so dense, they can be concentrated by homogenization and centrifugation, according to Arcand. This means less downstream processing steps. Further, each remaining step uses much smaller chromatography columns and other equipment, he says.
“When you think of it, the current secretion paradigm implies spending a fortune fishing out proteins from a vast proteolytic soup. Instead, the StorPro organelles allow for accumulation and concentration of an intact protein, and can therefore deliver significantly reduced manufacturing costs.”
Zera technology is currently being explored by 30 academic and commercial partners, Arcand reports. “They confirm that StorPro organelles can be induced to form in most eukaryotic cells including CHO cells, insect cells transfected using baculovirus, filamentous fungi, plant cells, whole insects, and whole plants.”
“The next step for ERA is to allow production scientists to quantify, protein by protein, the dollar-per-gram advantage of Zera/StorPro accumulation over secretion.”