Engineering Catalytic Bioscavengers

Background: The Joint Science and Technology Office (JSTO) of the Defense Threat Reduction Agency (DTRA) is interested in catalytic bioscavenger technologies that would eventually become FDA licensed products to protect the Warfighter against multiple organophosphorus nerve agents (OPNAs). To date, only one protein, human Butyrylcholinesterase (HuBChE), demonstrates the desired efficacy against all desired nerve agent target tested so far by binding OPNAs on a one to one basis. However, HuBChE requires administration of large quantities (hundreds of milligrams) of protein to confer protection against modest levels of OPNAs. A complementary or alternative approach is the development of bioscavengers that can catalytically degrade multiple OPNAs with a near diffusion-limited efficiency conferring an overall increase in protection against OPNA exposure. In addition to high catalytic efficiency, enzyme mutants must exhibit activity against all OPNA categories of interest and be similarly efficient in neutralizing all stereoisomers of each OPNA. Furthermore, the enzyme mutants must be able to afford at minimum an in vivo protective ratio ? 2LD50 for Soman or 4LD50 for Paraoxone. To date, bacterial organophosphate hydrolase (phosphotriesterases; PTEs), as exemplified by the recombinant PTE mutants (e.g., C23 and A53 scaffolds variants), have shown the most promise for the development of new MCM capability to afford protection against all G-type and V-type OPNAs. Capability Sought: The Respondent shall communicate its capability for the production and delivery of recombinant PTE mutants (e.g., C23 and A53 scaffolds) in accordance with the following criteria: 1. Employ a multidisciplinary approach combining computational design, directed evolution, and site-directed mutagenesis based on visual inspection of docked OPNA models, to enhance the catalytic activity of recombinant PTEs towards all G-type OPNAs and all V-type OPNAs and to increase thermal stability of the most active variants. 2. Produce recombinant PTEs with a threshold catalytic efficiency (kcat/KM) of ? 1 x 107 M-1min-1 towards different classes and stereoisomers (i.e. Rp-/Sp-isomers) of OPNAs. Response Instructions: Respondents shall address the information described above (and any additional information the respondent shall deem appropriate) via a Capabilities Statement (five-page limit) in Microsoft Word format. A rough order of magnitude (ROM) cost estimate for the services outlined above over a three-year period shall be provided. In addition, respondents shall include their name, address, CAGE code, and DUNS, and submit company size standard under the 541711 NAICS code. The information shall be submitted via e-mail to ayodele.o.olabisi.mil@mail.mil and devon.r.byrd.civ@mail.mil with a cc: to brian.d.nuckols.civ@mail.mil. Hard copy submissions will not be accepted. Submissions shall be submitted by no later than 2:00 pm local Ft. Belvoir time on the date specified within this notice. Disclaimer: This Sources Sought notice is solely for the purpose of gathering information and does not constitute a solicitation or the issuance thereof. All information received in response to this notice that is marked proprietary will be handled accordingly. Responses to this notice are not offers and cannot be accepted by the Government to form a binding contract. Any information submitted will not be returned, and no payment will be made by the Government for such information. No formal RFPs or other solicitations regarding this announcement are available at this time. Information provided herein is subject to change and in no way binds the Government to solicit for proposals or award contracts. It is the respondent's responsibility to monitor FedBizOpps at http://www.fbo.gov for the release of any subsequent information. DTRA is accepting questions regarding this notice but will not be providing responses. Primary Point of Contact: LCDR Ayodele Olabisi S&T Manager Chemical/Biological Technologies Department Defense Threat Reduction Agency ayodele.o.olabisi.mil@mail.mil