Agency: Department of Defense | Branch: Defense Threat Reduction Agency | Program: STTR | Phase: Phase I | Award Amount: 150.00K | Year: 2015
Future vaccine development should focus on rapid upscale production, long-term and broad protection, and sufficient global distribution to prevent and reduce the impact of many infectious diseases and potential epidemics. Agave BioSystems proposes to develop a novel whole-microorganism vaccine inactivation strategy involving high-throughput screen of extensive radio-protectant matrices and radiation doses using synchrotron X-ray irradiation, and subsequent in vitro analyses to determine the ideal condition for large-scale production on a gamma irradiator. To demonstrate the safety and efficacy of the resulting vaccines, Agave BioSystems will collaborate with our STTR partner Dr. Gary Whittaker and Dr. David Topham to use influenza viruses for proof-of-concept validation in Phase I. Our rapidly adaptable vaccine development strategy is applicable to a broad range of viruses and microorganisms, especially those particularly pathogenic and unsuitable for other conventional inactivation methods. The whole-organism based inactivation strategy enables both immediate and long-term immune protection. The process can be easily scaled up on a continuous irradiator to accommodate increased global needs.
Agency: Department of Defense | Branch: Air Force | Program: STTR | Phase: Phase II | Award Amount: 711.62K | Year: 2014
ABSTRACT: Protection of first responders who are exposed to hazards including chemical warfare agents (CWAs) is a very critical need. The need is derived from not only their welfare but their ability to respond, protect the community and provide logistical support to the response. A simple exposure monitor would provide critical information to the first responder and allow them to respond accordingly and to also help to monitor the environment. Exposure monitoring would also provide a more realistic picture of the threat with multiple points of sampling. Therefore, it would be useful to develop systems that could harness the body"s own chemistry to help detect the presence of CWA exposure in the field. CWAs are toxic because of their direct and indirect impact on biological processes in the human body. Agave BioSystems, in collaboration with Dr. Carl Batt of Cornell University are exploring nanoscale materials specifically tailored to create a new class of highly sensitive, robust and personal platform to determine military personnel exposure to OP CWAs. Agave BioSystems has demonstrated that the dye impregnated NPs are responsive to CWA simulants in a cellular environment. During the Phase II program, improved dye impregnated NPs and a prototype NP detector will be developed. The fluorogenic NPs will be incorporated into tattoos to create an in vivo biosensor capable of rapid detection of OP CWA exposure. BENEFIT: The possibility of CWA troop exposure to CWA agents is of major concern to the US military. A variety of systems exist to detect the presence of CWA agents in non-biological settings, but the exposure of humans to these agents can often go undetected until symptoms begin to appear. The development of a simple, biologically based system for detecting either acute or chronic CWA exposure would be of significant benefit to deployed military troops. In this STTR Phase II program, Agave BioSystems, in collaboration with Dr. Carl Batt of Cornell University, propose to develop a fluorogenic nanoparticle sensor that can be imbedded into the dermal layer of military personnel as a tattoo. This tattoo would have the unique characteristic of becoming fluorescent upon exposure to low levels of organophosphate CWAs. A small, hand-held optical sensor would then be used to record changes in fluorescence emitted from the tattoo, rapidly indicating exposure to potential CWAs. In addition to military personnel, civilian first responders are also at risk of exposure to organophosphate agents, either as CWAs dispersed by terrorists or as insecticides present in high concentrations at agricultural and industrial sites. First responders can include police, fire, and EMS personnel, as well as search and rescue, and National Guard troop. While the exact number of first responders in the US is not known, some estimate that there may be as many 10 million people who could be characterized as first responders. According to the Bureau of Labor Statistics, there were over 1.3 million professional and volunteer fire personnel, about 800,000 police, and about 250,000 EMTs and paramedics in the US alone. While it may not be necessary to use an implantable tattoo biosensor for detecting OP exposure in every first responder, the market for tattoos and fluorescence monitors for US military and National Guard troops, as well as police, fire and EMS personnel could be well over 1 million individuals. If even a small fraction (1%) of this number requires monitoring, the market for fluorescent biosensor tattoos and handheld monitors could exceed $10 million. In addition to the detection of OP CWAs and pesticides, implantable biosensors such as those described in this proposal, adaptation of this technology could readily yield biosensors capable of detecting a wide range of chemical contaminants, such as volatile organic compounds (VOCs) and toxic industrial chemicals (TICs). Potential diagnostic markets for VOC and related compound detection include homeland security, law enforcement and the military. The chemical modularity of the approach described herein should ably address the need for real time, field deployable sensors potentially capable of detecting myriad families of chemical toxicants in a multitude of settings. Upon completion of the Phase II program, Agave BioSystems will develop a detailed Phase III plan for the commercialization of the resulting technology.
Agency: Department of Defense | Branch: Army | Program: STTR | Phase: Phase II | Award Amount: 375.00K | Year: 2013
The chloroperoxidase enzyme from the filamentous fungus Caldariomyces fumago has applications in industrial chemical synthesis and the detection and inactivation of chemical warfare agents. Chloroperoxidase is capable of regio- and enantioselective oxygenations and halogenations of organic substrates. When performed chemically, these reactions typically require aggressive reagents and reaction conditions, and lead to the formation of undesired by-products. Widespread adoption of enzyme-catalyzed synthetic strategies is hindered by the high cost of purified proteins, and by the challenges of retaining the native activity of proteins expressed using heterologous host systems. In the Phase I, Agave BioSystems and collaborators from Cornell University achieved high level production of highly active recombinant Caldariomyces fumago chloroperoxidase (rCPO) in Aspergillus. The current not fully optimized levels of expression are five-fold higher than previously reported. They are also 100 fold lower than potential levels which have been achieved with other Aspergillus systems providing enormous upside potential that will be realized upon completion of the Phase II tasks. The result will be an expression system that meets or exceeds the sponsor"s specifications.
Agency: Department of Defense | Branch: Army | Program: SBIR | Phase: Phase II | Award Amount: 780.00K | Year: 2011
Dengue viruses are transmitted by mosquito vectors throughout tropical and subtropical regions of Asia, Africa, and Central and South America. Four serotypes circulate, DEN-1 through -4, and immunity to one type does not preclude illness from another type and can exacerbate subsequent disease with another type. While dengue fever can be a mild infection, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) cause death at a high rate and are associated with multiple serotypes worldwide. Dengue fever symptoms, especially at the early acute stage, can resemble infection with other disease agents, such as malaria and rickettsial diseases, with different treatment regimens. Loop-mediated isothermal amplification (LAMP) is a recently developed technique with similar or better detection sensitivity and specificity compared to PCR assays, but allows a single temperature incubation and simple readout more suitable to field devices. LAMP also offers the potential of detection in less pure samples, such as blood, facilitating quick field sample preparation. Therefore, Agave BioSystems proposes to develop a real-time reverse-transcriptase loop-mediated isothermal amplification (real-time RT-LAMP) diagnostic for detection of Dengue viruses in human serum.
Agency: Department of Defense | Branch: Army | Program: SBIR | Phase: Phase II | Award Amount: 780.00K | Year: 2012
Field testing of water samples is needed for broad and sensitive detection of toxic industrial chemicals, or TICs. The use of unicellular organisms in cell-based detection systems is particularly advantageous both because these organisms have developed a natural ability to respond to environmental changes, and because several methods for long-term storage with minimal maintenance requirements have been established and tested. Long-term storage of packaged freeze-dried cells with no need for significant environmental controls such as temperature eliminates limitations in the development of a rugged field-deployable device perfectly adapted to logistical requirements in a military setting. The need for a toxicant of interest to cross the natural barriers such as cell walls or membranes is perhaps the only significant limitation to the detection capability of any cell-based system. This will be addressed as part of the proposed effort by testing known genetic and biochemical approaches to the permeabilization of the bacterial cell wall to develop novel biosensors with broader and more sensitive detection capabilities. The Phase I established proof-of-concept for this novel biosensor. In the Phase II, a complete prototype will be developed ready for field testing.
Agency: Department of Health and Human Services | Branch: | Program: STTR | Phase: Phase I | Award Amount: 150.00K | Year: 2013
DESCRIPTION (provided by applicant): Agave BioSystems and Professor Makoto Kuro-o at the University of Texas Southwestern Medical Center are proposing a collaborative effort to screen for novel small molecules acting as agonists or antagonists of the Klotho and Klotho- dependent endocrine Fibroblast Growth Factors. The expected outcome of this Phase I effort will be the validation of a high-throughput screening methodology and the identification of confirmed hits which modulate the activity of endocrine Fibroblast Growth Factors FGF21 and FGF23. The effect of each hit will be confirmed in FGF- specific cell-based assays verifying changes in known activities of the Fibroblast Growth Factors. The small scale proof of concept screening campaign of the Phase Iwill be followed by a larger campaign in the Phase II do identify series of novel agonists and antagonists offering to uncover a broader set of structures and mechanisms of action for this novel effectors of endocrine Fibroblast Growth Factors. Selected hits will undergo early hit-to-lead optimization and be evaluated for cytotoxicity prior t small animal testing. Rodent disease models will be treated and the expected molecular, cellular and physiological changes of endocrine FGF activity modulation will be verified. This translational research project for therapeutic target validation will lead to the development of potential new drugs against chronic kidney disease, diabetes, obesity and cancer. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE:Agave BioSystems and Professor Makoto Kuro-o at the University of Texas Southwestern Medical Center are proposing a collaborative effort to screen for novel small molecules acting as antagonists of the Klotho-dependent endocrine Fibroblast Growth Factor FGF23 and as agonists of the Klotho-dependent FGF21. The identification of such compounds will be used for therapeutic target validation and potentially lead to the development of novel drugs against chronic kidney disease, diabetes, obesity and aging.
Agency: Department of Defense | Branch: Navy | Program: STTR | Phase: Phase I | Award Amount: 80.00K | Year: 2013
Agave BioSystems, with their academic partners at the Mote Marine Laboratory, proposes to develop probiotic pharmaceuticals from indigenous commensal microbes to enhance gastrointestinal health in the bottlenose dolphin (Tursiops truncatus). The dolphin gastrointestinal microbiome will be characterized by 16S rRNA deep sequencing, and culturable commensals will be isolated by plating dolphin gastric and fecal samples on a range of media. Cultured microbes will be tested for their ability to inhibit pathogen growth using a panel of known dolphin infectious agents, while qPCR assays will be developed to confirm the presence of the selected probiotic candidates in a sample dolphin population. A process for encapsulation of probiotic candidates will be developed to extend shelf life and confer resistance to degradation in gastric and bile environments. A Phase II plan will be developed to demonstrate the safety of the probiotic and evaluate its efficacy in the treatment of gastrointestinal disease in dolphins. Candidate probiotics will be characterized for colonization and adhesion and for their ability to modulate the host inflammatory response. Agave BioSystems will work with the US Navy Marine Mammal Program in the Phase II to demonstrate the performance of the probiotic at colonizing the dolphin intestine and promoting gastrointestinal health.
Agency: Department of Defense | Branch: Defense Advanced Research Projects Agency | Program: SBIR | Phase: Phase II | Award Amount: 1.00M | Year: 2013
Wound management becomes increasingly challenging due to bacterial infections, especially from epidemic drug-resistant strains. To address this problem, Agave BioSystems proposes to develop a RANT (Rapidly Adaptable Nanotherapeutics) breadboard system built upon the modules successfully established in Phase I of this work. The proposed breadboard system will use genomic sequencing data generated from wound pathogens to identify unknown pathogens and gene targets. These targets will serve as the basis for design of antisense PNA sequences to be incorporated into a PNA-CPP modified DNA nanoparticle. The pathogen-specific, ad hoc-developed nanoparticles are anticipated to possess characteristics of high efficacy, stability and penetration abilities to facilitate effective and specific elimination of emerging drug resistant microbes.
Agency: Department of Defense | Branch: Army | Program: SBIR | Phase: Phase II | Award Amount: 1.05M | Year: 2013
Bacterial enteric pathogens causing travelers diarrhea (TD) in developing countries include enterotoxigenic E. coli (50%), Camplyobacter jejuni, Shigella sonnei and Shigella flexneri, while Norovirus is a common viral cause. High risk regions for TD include areas where US service members are deployed. The rapid identification of immune responses to enteric pathogens would be advantageous to discovering potential vaccine candidates and defining exposures to enteric infections of interest. Enzyme linked immunosorbent assays (ELISA) are the current gold standard to measure serum antibody titers in response to enteric pathogens. However, ELISAs have significant limitations preventing their application in high-throughput screening of large sample numbers for multiple pathogens simultaneously. The difficulty of multiplexing ELISAs in a single well leads to increased usage of serum sample as well as reagents. Therefore, an assay is needed that can be multiplexed to detect several different pathogens in a single well and requires minimal technician time to perform. In this Phase I, Agave BioSystems demonstrated proof-of-concept for the use of flow cytometry microspheres in a multiplex assay to determine immunogenicity of candidate vaccines as well as prior pathogen exposure in blood. This novel multiplex microsphere-based assay will cover the most common causative pathogens of diarrhea.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2014
Clostridium difficile infection (CDI) results in excess of 14,000 deaths and over $1 billion in excess healthcare costs annually. Early and reliable diagnosis is key for both improving treatment outcomes, and instituting precautions to prevent transmission. Antibiotic therapy can actually increase the odds of coming down with a hospital-acquired infection, especially when the cause is a bacterium named Clostridium difficile. Currently there are no serologic assays for C. difficile toxins A and B. Such an assay would be advantageous for defining the epidemiology of CDI and selecting patients in whom to target future vaccines. The ideal serologic assay for CDI would measure circulating IgG and IgA antibodies to C. difficile toxin A and B as well as detect early and specific immunologic responses to these toxins. Agave BioSystems proposed to develop microsphere-based diagnostic assays to meet these objectives and to further develop the microsphere-based assay such that a single blood sample in a single well can detect toxin antibodies and early immunogenic responses to these toxins. These C. difficile microsphere assays will be developed sufficiently enough to differentiate patients that are susceptible for primary infection (asymptomatic), positive for colonization only and those that are likely to have CDI recurrence.