Request For Information for the Discovery of therapeutic countermeasures effective against newly emerging and genetically engineered pathogens.

The Defense Threat Reduction Agency (DTRA) is seeking technologies to enhance the development of medical countermeasures against novel biological threats. The enhanced technologies will enable the DoD to more rapidly respond to a biological event. The Transformational Medical Technologies Initiative's mission is to protect the Warfighter from potent known, naturally emerging, and genetically engineered threats by providing a response capability that begins with identification of pathogens and proceeds through the development of medical countermeasures. High priority organisms include hemorrhagic fever viruses and intracellular bacteria on the CDC Category A and B high priority pathogen list. Information Sought The TMTI program office requests information supporting methods, applications, and technologies that will greatly accelerate discovery of molecules useful as drugs for pre- and post-exposure prophylaxis or adjunctive treatments that contribute to increased survival benefit. Such molecules may focus on pathogen targets or they may concentrate on host (i.e., human cellular) machinery necessary for the pathogen life cycle. Specific topics of interest include: 3D Structural Models: TMTI seeks to: -Obtain models of target molecules (i.e., target proteins or nucleic acids) faster. -Develop higher resolution structures. -Determine how water molecules interact with the target and countermeasure molecules. -Develop a capability that would provide structure determination for membrane-bound proteins ID active site: -Identify more efficient, rapid processes and methods to identify the target active sites (primary & allosteric sites). -Develop a priori methods to identify the active site. ID Molecules: -In silico drug design of novel antimicrobial and antiviral agents. -Develop quantitative structure-activity relationship (QSAR) methods and strategies, including methods to reduce data dimensionality. -Optimize design of experiments (DOE) to decrease the number of inactive molecules before they are synthesized; this may include appropriate simulations, methods, or calculations for high dimensional data common in QSAR's. -Create libraries or databases of druggable molecules before an outbreak of viral or bacterial threats. Synthesize: -Develop strategies or processes to more rapidly synthesize druggable compounds within a short timeframe, which could include the use of robotics. Target Infected Cells: -Develop strategies and processes to more effectively infected target cells. -Develop systems that will selectively release drug payload within infected cells. NCE Delivery: -Solutions from domains outside of biodefense related-research (e.g. HIV, cancer, sepsis, trauma) are encouraged. These technologies may be used as stand-alone technologies or integrated into a larger response architecture. -Develop novel systems that will deliver therapeutic quantities of drugs through both host and pathogen membranes. -Develop novel methods to deliver drug under battlefield conditions, including intramuscular auto-injection, pulmonary delivery, etc. -Discover methods to stabilize NCE's to allow storage at room temperature and above, thus minimizing cold chain requirements. -Improve the pharmacokinetics of NCE's to avoid frequent dosing. Instructions to Responders Sources having the capability and/or concept to meet these requirements are invited to respond to this RFI. Responses should be limited to five (5) pages for any given concept, not including cover page, cover letter and table of contents. Any proprietary concepts of information should be clearly identified as such. Submitted data and information will not be returned. Input on technical aspects of the responses may be solicited by DTRA from non-government consultants/experts who are bound by appropriate non-disclosure requirements. For all RFI responses, an additional, non proprietary cover page is also requested identifying your company name, technical point of contact, and contact information. This is a Sources Sought Synopsis/ Request for Information (RFI). There is no solicitation available at this time. Requests for Solicitation and inquiries related to same will not receive a response. This RFI is published for market research purposes only, and in no way obligates the Government to issue a solicitation or otherwise make a contract award. Any and all information submitted in response to this synopsis is strictly voluntary. The Government will not pay for any information submitted in response to this RFI. Only electronic submissions of information provided to the email address specified will be accepted. RFI responses should be sent to the following email address: contact@example.gov. All emails should include in the subject line the RFI number and the submitting organization's name. Responses should be submitted electronically not later than 5:00 p.m. EST on 01/22/2010.