As part of Bristol-Myers Squibb (BMS) Company’s continued quest to develop improved production processes for paclitaxel (Taxol), the company will commercialize a proprietary plant cell fermentation process for the drug developed by Phyton Inc. ( Ithaca, NY). Phyton originally licensed this technology to BMS exclusively in 1995. Under the current agreement, BMS retains the rights to produce taxol and related compounds using the fermentation of plant cells. But little Phyton (72 employees) could become a major pharmaceutical player by licensing its production methods for other products, which the company is currently discussing with two other pharmaceutical companies.
Taxol is marketed by BMS in the United States and internationally for the treatment of ovarian and breast cancer. Recent studies have shown that Taxol can prevent breast cancer in women at risk, but the drug’s toxicity obscures this potential high-risk indication.
Plant Cell Fermentation
Taxol was originally isolated from Pacific yew, but the extraction process is expensive and conservationists oppose destroying slow-growing trees to obtain the drug. The total synthesis is out of the question, except as an academic exercise. Since 1994, BMS has used a semi-synthetic method to produce paclitaxel from an intermediate derived from renewable biomass such as twigs and needles of yew trees. This process involves isolating taxol-like molecules and performing several chemical steps on them. Again, this technique is time consuming and expensive because the structure of taxol is so complex and labile.
Due to the complex structure of taxol, total synthesis on a commercial scale is impractical
Phyton’s Plant Cell Fermentation (PCF) technology represents a potentially large-scale method of producing paclitaxel and related taxen molecules without synthesis and harvesting the product from cultivated plants. â€œPCF harnesses a plant’s production of secondary metabolites in response to stress,â€ said CEO Kris Venkat. “Our technology involves selecting cell lines from the right species of yew, cultivating them in a way that does not induce the cells to differentiate into plants, and introducing the right environmental factors to promote taxol production over other phytochemicals. ”
Plant cell fermenters could produce large
amounts of taxol, saving hundreds of
dollars per dose versus semi-
synthetic production by sparing
To this end, Phyton has dedicated 250 person-years. The company’s fermentation facility, located in Germany, uses a 75,000 liter fermenter (the world’s largest PCF), capable of producing hundreds of kilograms of taxol in a single batch.
â€œThe large scale is essential,â€ Venkat told Pharmaceutical Online, â€œBecause taxol is a high dose drug. It’s not like monoclonal antibodies, which are often produced in a 20-liter fermenter or in a small colony of mice. ”
To date Bristol-Myers Squibb has invested over $ 25 million to develop PCF technology with Phyton (taxol sales are expected to exceed $ 1 billion in 1998). Phyton will receive additional funding, milestone payments and royalties on sales of TAXOL products.
For more information: Kris Venkat, CEO, Phyton, Inc., 125 Langmuir Laboratory, 95 Brown Rd., Ithaca, NY 14850-1257. Phone. : 607-257-5058.
By Angelo DePalma