The overall goal of the proposed R&D program is to develop improved methodologies and manufacturing processes for the isolation of the marine natural product bryostatin 1 which is derived from the marine byrozoan Bugula neritina. Bryostatin 1 is currently in Phase II clinical trials in the US against melanomas, lymphomas and renal cells. While harvesting the bryozoan with consistent sources of the active agent will become a significant portion of the supply problem, large-scale manufacturing of the natural product agent will also pose significant challenges to processing logistics and manufacturing costs. In our Phase I research effort, we showed that supercritical fluid extraction and chromatography techniques can be utilized to very rapidly isolate bryostatin I from Bugula with several hundred fold (370) improvements m purity in times less than 30 minutes, with very high recovery efficiencies (approximately-100%), and in an environmentally friendly manner. In our Phase II R&D effort, we plan to further improve the supercritical fluid process and modify an existing pilot-plant for the isolation of ultra-pure bryostatin 1. We plan to collaborate with CalBioMarine who will supply both naturally occurring and aquacultured quantities of the """"""""sea moss"""""""" B. neritina.
The developed process will facilitate the manufacturing of bryostatin 1 and therapeutic analogy and increase their availability for preclinical and clinical use by the National Cancer Institute, and pharmaceutical companies such as Bristol-Myers Squibb.
