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Novel Agents for Gram-Negative Biodefense Pathogens (CRADA Final Report)

Technical Report ·
DOI:https://doi.org/10.2172/1084458· OSTI ID:1084458
 [1];  [1];  [2]
  1. Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
  2. Truis Therapeutics, San Diego, CA (United States)

This was a collaborative effort between Lawrence Livermore National Security, LLC as manager and operator of Lawrence Livermore National Laboratory (LLNL) and Trius Therapeutics, Inc. ("Trius") to develop novel agents for gram-negative biodefense pathogens. LLNL and Trius jointly responded to a U.S. Health and Human Services (National Institutes of Health) request for proposals (solicitation # BAA NIH-NIAID-DMID 08-20) to develop new therapeutic countermeasures with a proposal entitled "Development of Therapeutic Agents for Select Biodefense Pathogens" which resulted in this CRADA, with a goal of developing gram-negative, dual-target antibacterial agents that show no cross-resistance to existing drugs. Trius was awarded Contract HHSN272200800042C to accomplish the goals in the proposal, with LLNL as a major subcontractor. The technical objectives of this CRADA project were to develop a new therapeutic entity with activity against gram-negative category A and B biothreat agents. The therapeutic would be a small molecule that could be administered intravenously (i.v.), preferably once- or twice-a-day and would be available for use both as a prophylactic and as a therapeutic against a wide range of biodefense pathogens. These included the gram-negative biodefense pathogens: Escherichia coli, Salmonella (enterica and Typhi), Shigella dysenteriae, Yersinia pestis, Burkholderia pseudomallei, Campylobacter jejuni and Francisella tularensis, as well as potentially the Category A gram-positive pathogen Bacillus anthracis. This new therapeutic will act through inhibition of bacterial DNA topoisomerase IV and DNA gyrase (ParE and GyrB, respectively).

Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States); Truis Therapeutics, San Diego, CA (United States)
Sponsoring Organization:
USDOE; National Institutes of Health (NIH)
DOE Contract Number:
AC52-07NA27344
OSTI ID:
1084458
Report Number(s):
LLNL--TR-638984; LLNL--TR-745528-Rev.2; TC02128.0
Country of Publication:
United States
Language:
English

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