U.S. ARMY MEDICAL RESEARCH ACQ ACTIVITY, ATTN: MCMR-AAA-J, 820 CHANDLER STREET, FORT DETRICK MD 21702-5014

A -- DEVELOP: 1) A SCALEABLE PURIFICATION PROCESS, AND 2) AN OPTIMAL FERMENTATION PROCESS -- FOR BONT F (HC) VACCINE CANDIDATE SOL W23MYC-8125-N014 POC Contracting Officer Daniel R. Signore (301)619-7423 dan_signore@ftdetrck-ccmail.army.mil (Site Code DAMD17) (Site Code DAMD17) The U.S. Army Medical Research and Materiel Command anticipates awarding a sole source order for commercial services with Covance Biotechnology Services, Inc. for a period of 14 weeks to: 1) develop optimal fermentation conditions for producing maximal expression of an intact vaccine product from the Government provided clone, and 2) develop analytical ELISA or other method for determining levels of product resulting from expression of product when conditions for the fermentations are varied. The proposed work will consist of The Government providing the contractor with a Pichia pastoris clone harboring the synthetic gene encoding a non-toxic fragment C (Hc) region of a botulinum neurotoxin (BoNT) serotype F. This clone has been shown to express a product having the expected molecular weight of rBoNTF(Hc) on Western blot analysis. The Government will also provide immunological reagents for assaying the rBoNTF(Hc). The contractor will determine optimal fermentation conditions for this Pichia pastoris clone such that fermentation of this clone using these conditions will provide optimal conditions for maximal expression of an intact vaccine product from the clone. The contractor will also develop a purification process that shall remove contaminating host proteins, nucleic acids, and other host cell components from the recombinant vaccine product. The level of purity to be greater than 95% homogeneous. Methods used to purify the recombinant product will be conventional chromatography such as cation and anion exchange chromatography, hydrophobic chromatography, or other methods acceptable to the Center for Biologics Evaluation and Research (CBER). The purification process developed by the contractor shall be tested at a scaled-up level processing at least 1 to 3 kg of yeast cells. Justification: Covance is the planned recombinant botulinum vaccine subcontractor to DynPort, the Army's prime contractor for vaccine development, licensure, and production. If the above project were awarded to anyone other than Covance, it would result in a duplication of effort at a future date by Covance. All responsible sources must provide written documentation demonstrating identical capabilities with Covance Biotechnology Services, Inc. to the above address by 1 July 98. (0169)

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