Accelerated Monoclonal Antibody Bio-fermentation (AMAB)

Accelerated Monoclonal Antibody Bio-fermentation (AMAB) RFI DARPA-SN-09-21; Responses due March 20, 2009. POC Michael Callahan, DARPA/DSO; Phone: (571) 218-4596 Fax: (703) 807-4945 DESCRIPTION The Defense Sciences Office (DSO) of the Defense Advanced Research Projects Agency (DARPA) is seeking ideas that may support a new DARPA program to demonstrate innovative concepts and technologies that dramatically shorten the timelines for production and purification of monoclonal antibodies at >5 g/(kilogram wet biomass or liter bioreactor). The first anticipated AMAB goal, should a program be established, would be to identify novel expression technologies suitable for the accelerated production of large quantities (5 million doses using 400 mg/dose each) of low-cost (<$10/dose) IgG full length monoclonal antibodies (mAb) in less than 10 weeks. The description of ideas for realizing such a platform should emphasize cost per dose, folding, glycosylation, and di-sulfide bond formation. The second anticipated goal of AMAB would be to identify novel protein purification processes and technologies that can be scaled to accommodate the production of 10-50 thousand doses of mAb per day while maintaining the low cost of goods manufactured. Although not a major goal, DARPA is also interested in purifications processes that do not require protein A for IgG purification. DARPA is interested in detailed submissions that provide ideas on new approaches to achieving the maximal possible production titer (>5 g/ (kilogram wet biomass or liter bioreactor) that can be achieved within a 6-month period of performance or less. Ideas related to automated and high-throughput applications of pre-existing processes and technologies and incremental advances of current technologies should not be submitted. REQUESTED INFORMATION DARPA appreciates responses from all capable and qualified sources, including but not limited to, universities, university affiliated research centers, and private or public companies. To ensure that all technically relevant aspects of the RFI are fully addressed, technologies and capabilities should target the following criterion: 1. Novelty: Of particular interest are novel expression platforms and innovative purification technologies uniquely suited for expression of monoclonal antibodies. Intellectual property should be clearly established and allow full freedom of operation. Specifically excluded from this RFI are mammalian production systems. 2. Resiliency: Platform should have documented ability to produce properly folded and disulfide bonded monoclonal antibodies. Proper glycosylation is encouraged, but is not required. Primary data is strongly encouraged. 3. High quality: Resultant monoclonal product should be soluble, free of fragments, and have proper folding verified by biophysical analysis (CD, NMR, Crystallography, Cryo-EM). 4. Low cost: Documented cost analysis, including an estimate for production under cGMP, should be available for review. The responsiveness of cost to production titer should be indicated. All major cost areas including subcontracted cGMP contract manufacturing organization (CMOs; if applicable) must also be included. 5. Speed: To address the pressing need to produce large quantities of novel medical countermeasures on an abbreviated timeline, successful submissions should have the capability to start with non-optimized cDNA to produce batches of >10,000 doses (400mg/dose) in 12 weeks or less. 6. Market readiness: As the goal of this RFI is to identify novel technologies for the expression of proteins for use as therapeutics, information describing a pathway to cGMP production is relevant and should be included. Additionally, a cGMP risk analysis specific to the expression system will support a successful submission. This should include common adventitial agents, possible sources of contamination, and possible sources of pyrogenic material. INSTRUCTIONS TO RESPONDERS When responding to this RFI, please include examples of successful protein expression, titers of purified proteins, and approaches that might improve titer. Experimental demonstration of efficacy in animal models or information about currently licensed products is of particular interest. Acknowledged technological barriers to accomplishing this goal include protease susceptibility, DNA optimization, promoter development, biofermentation conditions, scale-up, and purification. An analysis of unique, limiting, and/or hard to find reagents required for the expression platform or purification technology should be discussed in order to develop a risk mitigation strategy. FORMAT Responses should adhere to the following formatting and outline instructions: 1. Format specifications include 12 point font, single spaced, single-sided, and 8.5 by 11 inches paper, with 1-inch margins. All submissions must be electronic, adhere to the format described below and use one of the following formats: Adobe PDF or Microsoft Word. 2. Cover Page (1 page) a. Title b. Organization c. Responder's technical and administrative points of contact (names, addresses, phone and fax numbers, and email addresses) 3. Technical areas (up to 8 pages) a. A technical description of the platform including but not limited to its novelty, resilience, and limiting reagents (4 pages) b. Examples of success (1 page) c. Identify the clinical and toxicological data (if any) (1 page) d. Cost estimate per dose and market readiness (2 pages) BUDGET This is a Request for Information (RFI) only. A budget does not need to be included at this time. Additionally, we request that you submit a Microsoft PowerPoint slide presentation, not to exceed six slides, addressing the technical aspects of the response. SUBMISSION Responses to this RFI should be submitted to CallahanMeeting@darpa.mil. Please refer to the "AMAB RFI" in all correspondence. All technical and administrative correspondence and questions regarding this announcement should also be submitted to the same email address. DISCLAIMERS AND IMPORTANT NOTES This is an RFI issued solely for information and new program planning purposes; it does not constitute a formal solicitation for proposals. In accordance with FAR 15.201(e), responses to this notice are not offers and cannot be accepted by the Government to form a binding contract. Submission is voluntary and is not required to propose to a subsequent Broad Agency Announcement (BAA) (if any) or other research solicitation (if any) on this topic. DARPA will not provide reimbursement for costs incurred in responding to this RFI. No proprietary or classified information should be submitted. Respondents are advised that DARPA is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted under this RFI. In the event of a subsequent BAA or other solicitation, all information submitted in response to this RFI will be considered public information and will be provided on a public website. NO PROPRIETARY OR CLASSIFIED INFORMATION SHOULD BE INCLUDED IN THE RFI RESPONSE. It is the responder's responsibility to ensure that the submitted material has been approved for public release by the organization that funded the research.