Antibody Technology Program
On August 31, 2009, DARPA solicited proposals for "innovative research towards developing and demonstrating the ability to simultaneously improve antibody stability and control antibody affinity. The goal of the Antibody Technology Program is to enable multiplexed, antibody-based biosensors that have long shelf life and operate in harsh environments that are relevant to the DoD mission." http://www.darpa.mil/dso/solicitations/baa09-69.htm
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According to DARPA's DSO:
Antibody-based biosensors provide the most reliable detection capability across the broadest range of biowarfare agents. They are, therefore, the preferred platform for DoD biosensor applications. However, the fragility of the antibody molecule together with the short shelf life (typically two weeks or less) of antibody-based biosensors severely complicates their use outside of a clinical laboratory environment. In addition, the variability in affinity across various antibody systems has precluded the development of multiplexing antibody arrays for biosensor applications. The vision of the Antibody Technology Program (ATP) is to develop and demonstrate approaches for achieving revolutionary improvements in the stability of antibodies while simultaneously demonstrating the ability to control antibody affinity. DARPA believes that achievement of these goals will ultimately enable the deployment of portable, multiplexing biosensors that operate robustly and reliably in harsh environments relevant to the DoD mission.
Under the ATP BAA, DARPA is soliciting innovative, two-phase research proposals that address the need for developing and demonstrating antibody modification strategies that enable high stability and controllable affinity. The primary goals of the ATP are to develop and demonstrate technologies that will enable antibody-based biosensors that operate in harsh environments and which may be stored at 20-25° C for future use for up to 5 years with no loss in performance. Additionally, the ability to control antibody affinity will enable the development and deployment of biosensor arrays that detect multiple agents in a single platform. It is anticipated that technologies developed under ATP will be readily applicable to a broad range of antibodies with relevance to the DoD mission. DARPA believes that achieving the ATP goals will revolutionize DoD capabilities for detecting biowarfare agents for future missions. DARPA is not interested in research that primarily results in evolutionary improvements to the existing state of practice in biowarfare agent detection.
DARPA seeks innovative, two-phase proposals that incorporate all of the following Areas of Interest:
Phase I
The Phase I program should describe a technology development and demonstration plan of duration not to exceed 12 months that addresses the technical areas listed below in viral antibody molecules that will be provided to performers by the Government.
Technical Area One: Develop and demonstrate strategies for achieving antibody stability from room temperature up to temperatures of 70° C or greater.
Thermal instability and short shelf life are major limitations of antibody based biosensors that largely complicate their deployment outside of a clinical laboratory environment. Strategies for improving antibody stability should be generically applicable to a broad range of antibodies with relevance to DoD applications and should enable antibody function over a wide range of temperatures from 20° C up to at least 70° C which may eliminate the need for refrigeration. The achievement of stability cannot be attained at the expense of antibody function or affinity.
Technical Area Two: Develop and demonstrate strategies for achieving controllable antibody affinity.
Strategies for demonstrating controllable antibody affinity should be generically applicable to a broad range of antibodies with relevance to DoD applications and should result in the ability to tune antibody affinity, as measured by the disassociation constant (Kd), to a value of 10-8, or the enhancement of at least two orders of magnitude increase in affinity of the antibody (provided by the Government). The binding constant for the antibody will also be provided by the Government. The achievement of affinity cannot be attained at the expense of antibody stability.
DARPA is not interested in proposals that describe “brute force” or combinatorial approaches that lead to fortuitous improvements in stability or affinity. The strategies explored in ATP must lead to new understanding of mechanisms for controlling stability and affinity and which can reasonably be assumed to be transferable to other antibody molecules.
Phase II
Technical Area Three: Demonstrate the ability to simultaneously achieve high stability and controllable affinity in a single antibody molecule.
While the Phase I program allows for stability and affinity controls to be demonstrated in separate antibody molecule, the Phase II effort must demonstrate the transferability of the Phase I strategies to a single antibody molecule while still achieving the stability and affinity goals demonstrated in Phase I. To this end, proposers are expected to describe a Phase II program that will demonstrate the ability to simultaneously achieve stability and controllable affinity in a “master” antibody molecule. The choice of antibody/antigen system will be solely at the Government’s discretion and will be made known to the performers prior to any Phase II award.
Technical Area Four: Demonstrate the advantage of the ATP “master antibody” in an existing biosensor platform.
Upon consultation with the DARPA program manager, performers under an ATP Phase II award will have their “master antibody” system assessed by an independent Government laboratory in order to determine the robustness and multiplexing advantages of the antibodies in an existing biosensor platform.
http://www.darpa.mil/dso/solicitations/baa09-69.htm
http://www.darpa.mil/dso/solicitations/baa09-69.htm
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