Cell Therapeutics, Inc. (CTI, Seattle, WA, www.ctiseattle.com), has formed a new spin-off company, Aequus BioPharma, Inc., to develop a novel process to extend the half-life of proteins. According to the company, the new process will be a cheaper alternative to existing technologies.
For years, biopharmaceutical manufacturers have been using chemical modification techniques to increase the relatively short plasma life of protein therapeutics. The most commonly used method is chemical conjugation with polyethylene glycol (PEG) after the protein is expressed.
In CTI’s technology, a polymer is attached to the therapeutic protein during the expression process, thus eliminating the need for later steps. “CTI’s technology doesn’t require chemical modification, so it comes at a lesser cost,” says CTI’s President and CEO James A. Bianco, MD. “This is a single-step biological process, as compared with multistep chemical conjugation, which involves expressing and purifying the protein, modifying it chemically, and purifying it again before production,” he adds. “So manufacturing costs are lower.”
The company’s “genetic polymer” technology is a recombinant DNA process that combines three components—a signal sequence, a biologically active protein sequence, and a polyamino acid sequence—to form a novel gene. “You are essentially making a new vector that has the entire sequence,” explains Bianco. “When you transfect the cell and that entire sequence is read, you produce a long-acting protein recombinantly.” According to Bianco, the Genetic Polymer technology has the potential to extend the half-life of a protein from 1 to 30 days.
The polymer technology can be used for multiple molecules, which may eliminate the need to develop individualized technology for extending the plasma half-life of each biopharmaceutical, says Bianco. Also, because the polyamino acid sequence produced is biologically inactive, it could speed up the development and commercialization of follow-on biologics if the US Congress approves the legislation. “The new sequence doesn’t change the active ingredient but only affects the half-life,” says Bianco. “Therefore, the new protein would be comparable and need only an expedited clinical route.”
This recombinant technology also might be used to develop novel biologics and deliver small inhibitors of RNA (siRNA) to their cellular targets in a wide array of malignant, inflammatory, or infectious diseases. CTI has begun recruiting a scientific and management team with the requisite experience in protein therapeutics to take the lead on this new venture to speed follow-on biologics to market and patients.
CTI says it has demonstrated a preliminary proof of principle of the genetic polymer technology and that Aequus BioPharma plans to generate additional experimental data to validate the technology. The first biologics the company plans to move into preclinical study include a long-acting granulocyte-colony stimulating factor (G-CSF), interferon, and erythropoietin.