NCI Frederick Cancer Research and Development Center (NCI-FCRDC), P.O. Box B, Frederick, Maryland 21702-1201

A -- CHIMERIZE OR HUMANIZE MONOCLONAL ANTIBODIES AND OTHER TARGETING AGENTS SOL S00-94 DUE 011200 POC Heather Wells -- 301-846-1520 E-MAIL: Click here to contact the contracting officer via., hwells@mail.ncifcrf.gov. A. The National Cancer Institute (NCI) has established the Rapid Access to Intervention Development (RAID) Program that is designed to assist extramural investigators, by the use of NCI contract resources, in their development of pre-clinical and clinical agents (both drugs and biologics) that will be tested ultimately in human clinical studies. B. As part of the RAID initiative, SAIC Frederick, a Division of Science Applications International Corporation (hereafter "SAIC Frederick" or "SAIC") under its contract with the NCI, Frederick Cancer Research and Development Center, seeks a Contractor to chimerize or humanize monoclonal antibodies and other targeting agents that have shown promise as the murine version, for the treatment of human disease. C. The NCI requires production of mammalian cell clones producing the chimerized form of a murine monoclonal antibody known as 11-1F4, an antibody developed by the Principal Investigator (PI), Dr. Alan Solomon at the University of Tennessee at Knoxville. The PI and his colleagues have used an experimental in vivo model to demonstrate that this antibody binds to and accelerates the removal of human light chain-associated (AL) amyloid extracts implanted subcutaneously in Balb/c mice. The PI intends to test the "amyoidolytic" capacity of the chimeric antibody in this model system and compare its activity with the parental murine construct, for binding affinity to antigen. D. Independently, and not as an agent of the Government, the Contractor shall furnish services, qualified personnel, materials, equipment, and facilities, not otherwise provided by the Government (or from the PI) to perform the Statement of Work (SOW): -- SOW -- General 1. The Contractor shall use proven recombinant genetic methods to construct chimeric immunoglobulin genes, insert these genes into suitable vectors and transfer the vectors to an appropriate mammalian expression system for the production of the chimeric antibody, 11-1F4. 2. The Contractor shall provide the human constantregion genes, all enzymes and other reagents for the completion of the project, including cell culture media, as well as the expression cell lines. Methodology The Contractor shall perform the following specific tasks: 1. Generate clones of cells capable of producing the murine-human chimeric monoclonal antibody 11-1F4. Because of the possibility that these clones will be used to make clinical-grade monoclonal antibody, the use of selection markers and media components must be compatible with current Good Manufacturing Practices (cGMP). 2. Select clones (at least three (3) independent clones) that secrete large enough quantities of chimeric antibody so that scale-up production is practical and cost-effective, i.e., at least 50 mg/ml per 106 cells over four (4) days of stationary culture. 3. Demonstrate that the selected clones produce a momogeneous product, i.e., free of extraneous immunoglobulin chain production and secretion, and that the product is not susceptible to degradation or aggregation. 4. Demonstrate that the selected clones produce a chimeric antibody with the same specificity as the original murine antibody and an affinity equal or greater than the original murine antibody. 5. Demonstrate that the clones are free from adventitious agents as determined by mycoplasma and MAP testing. 6. Deliver 20mg of purified (>95% pure by SDS-PAGE) chimeric 11-1F4 from each of three independent clones. The antibody should be concentrated to 5mg/ml and dispensed into vials at 0.5ml/vial. Posted 12/21/99 (W-SN410647). (0355)

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