A -- Development of a Final Drug Product for a Mixture of Monoclonal Antibodies for Types A, B and E Botulinum Neurotoxins

The National Institute of Allergy and Infectious Diseases (NIAID), NIH, DHHS, intends to negotiate a multiple-year contract to develop a monoclonal antibody (MAb)-based treatment for botulism caused by botulinum neurotoxin serotypes A, B and E (BoNT/ A/B/E) with XOMA, LLC, under the authority of 41 U.S.C. 253(c)(1), as set forth in FAR 6.302-1(b)(1) and HHSAR 306-302-1(b)(1) -- unique supplies or services available from only one source. XOMA is currently developing three MAbs (NX01, NX02 and NX11) that potently neutralize BoNT subserotypes A1 and A2 under contract N01-AI-60008. The proposed contract will identify MAbs that potently neutralize BoNT/B and E (and their major subserotypes), develop those MAbs for commercial production, and formulate a final drug product that potently neutralizes BoNT/A/B and E and includes the three BoNT/A MAbs (NX01, NX02 and NX11). XOMA is in a unique position to immediately continue the development of this high priority biodefense product. To develop NX01, NX02 and NX11, XOMA fused human variable region sequences (generated by Dr. James Marks, UCSF and accessed through a material transfer and evaluation agreement with UCSF) to XOMA's proprietary modular antibody expression vectors containing light and heavy chain constant regions. The use of this same antibody framework for new BoNT/B and E MAbs may significantly increase the likelihood that the additional MAbs will share physical/chemical characteristics with NX01, NX02 and NX11, and, therefore increase the likelihood that they can be formulated together. The co-formulation of a large number of MAbs is novel and could present a technical hurdle to this program and thus any technical approaches that increase the likelihood of successfully co-formulating the MAbs should be pursued. The proprietary XOMA framework has been used in MAbs that have been evaluated in humans for safety and immunogenicity and were shown to be safe and relatively non-immunogenic. XOMA has experience with all of the assays that are required to characterize the MAbs, including the mouse neutralization assay. XOMA's proprietary technology includes the commercial expression cell line that was used to produce the Master Cell Bank and the Working Master Cell Bank for the three BoNT/A MAbs. The use of the same cell line for expression of the BoNT/B and E MAbs will streamline the regulatory pathway for the approval of these MAbs to be evaluated in humans. In summary, applying identical technology to the new BoNT/B and E MAbs will reduce the timeframe for their development, increase the likelihood that all the MAbs can be formulated together, reduce the risk of safety/immunogenicity problems, and streamline the regulatory review. This project has not been reviewed by the Board of Scientific Counselors as required. Such review will occur prior to technical evaluation. Thus potential offerors are cautioned that cancellation of this RFP due to disapproval by the Board of Scientific Counselors is a possibility. If there are responsible sources who feel that they are able to perform the requirement, they must respond by the closing date noted above. See Numbered Note 22. No collect calls will be accepted.