Aphios Granted United States Patent for the Crystallization of Complex Molecules such as Taxol
May 07, 2001
Woburn, MA — Aphios Corporation today announced that it was granted United States Patent No. 6,221,153, entitled "Method for Producing Large Crystals of Complex Molecules," on April 24, 2001.

This invention relates to methods for making highly ordered, large-size crystals of complex molecules such as paclitaxel (Taxol™) and Bryostatin 1, both potent anticancer drugs. The methods, by virtue of the nature of the crystal product, have utility in purification processes, quality control, material handling and as tools for qualitative analysis and rational drug design. The invention features the use of critical, supercritical or near-critical fluids, compressed gases, and/or liquefied gases that are utilized as antisolvents. Such antisolvents are added to a solution containing a solute such as paclitaxel. The addition of critical, supercritical or near-critical fluids, compressed gases, and/or liquefied gases changes the nature of the solution, forcing the solute to leave the solution as large-size, highly ordered crystals.

Crystallization is an important step in the purification of organic materials, in particular, natural therapeutics. Improved crystallization processes can provide routes to higher purity final products. Such high quality, pure crystals are of great value for a variety of industrial and research applications. They can be utilized to resolve a frequent problem in pharmaceutical research - the difficulty of obtaining large single crystals for X-ray structural analysis to determine molecular conformations.

Crystallization is also frequently used as a method of purification in the biotechnology and pharmaceutical industries. Higher ordered crystals will typically result in a more highly purified product. Larger crystals can also impart advantages in packaging and handling operations, and in the manufacturing of controlled release materials.

Through the use of supercritical and near-critical carbon dioxide with small molar quantities of a cosolvent (SuperFluids™), Aphios has crystallized the anticancer drug paclitaxel (molecular weight 854) in considerably larger crystal size, improved morphology, higher purity and improved yields than can be achieved by conventional organic phase techniques. The worldwide marketplace for Taxol™ was in excess of $1.6 billion in 2000. Dr. Trevor Castor, President and CEO of Aphios Corporation, states, "To our knowledge, these are the largest and most well-ordered paclitaxel crystals grown to date." The SuperFluids™ CRY (crystallization) process was also successfully utilized to crystallize Bryostatin 1 (molecular weight 905), a marine natural product and an anticancer compound now in Phase II clinical trials sponsored by the National Cancer Institute.

Additionally, Aphios isolates and manufactures an all-natural Taxol™ from the needles (leaves) of the yew tree by utilizing a SuperFluids™ process that is cost-effective and environmentally friendly [US Pat. No. 5,440,055, Aug. 08, 1995]. The Company is developing an enhanced liposomal formulation of paclitaxel called Taxosomes. Research has demonstrated that Taxosomes are more effective and less toxic than Taxol [US Pat. No. 5,554,382, Sept. 10, 1996, and US Pat. No. 5,776, 486, July 07, 1998].

Taxol™ - Registered Trademark of the Bristol-Meyers Squibb Company

SuperFluids™ - Trademark of Aphios Corporation