Many widely used therapeutically important peptide drugs and hormones (annual international sales: $13 billion) are cyclized by means of disulfide bridges. However, the production of these peptides is difficult and expensive, due to formation of numerous by-products. Current technology requires extensive purification, which leads to lower yields and purities and results in high annual production costs. Our Phase I study produced a solid polymer-supported oxidant, termed CLEAR-OX(TM), that successfully forms cyclic peptides. These improved synthetic conditions allow rapid purification through simple filtration. Product yields and purities were often better than those obtained by existing strategies. Since this SBIR program was last reviewed, additional studies have been carried out on particularly challenging cyclizations; these showed how use of CLEAR-OX(TM) led to increased purities and yields with dramatic decreases in reaction times. Together, these improvements will significantly lower annual production costs. Our Phase II prototype will be developed and tested in discrete steps in the following manner: (1) prototype optimization of the polymer-supported oxidant to demonstrate broad applicability; (2) quality control testing measured by the successful synthesis of bioactive drugs; (3) manufacturing process scale-up; and (4) commercial product usage studies of CLEAR-OX(TM). Our successful Phase I study indicates a commercially viable polymer-supported reagent will result from a Phase II project. We envision a successful commercialization plan to produce CLEAR-OX(TM) for leading pharmaceutical and research organizations developing disulfide-bridged peptide drugs. Currently, no such commercial product exists. The commercial impact of this product could reach as much as $50 million.
