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Berkeley, CA, United States

Lumiphore, Inc. | Date: 2010-12-23

The invention provides compounds such as chelating agents useful in chelating metal ions, particularly radionuclides, to provide metal ion complexes. The invention also provides methods of using the compounds and complexes of the invention, such as in therapeutic and diagnostic applications.

Agency: NSF | Branch: Standard Grant | Program: | Phase: | Award Amount: 598.88K | Year: 2012

This Small Business Innovation Research (SBIR) Phase II project addresses challenges found with the current methods of microscopic imaging of protein-protein interactions in living cells. These methods rely extensively on Förster Resonance Energy Transfer (FRET) between cyan (CFP) and yellow fluorescent proteins (YFP). These methods are problematic, due to the interference from background noise and the intrinsic photophysical properties of these fluorophores. We have developed a system that uses a lanthanide complex donor in combination with time resolved fluorescent microscopy, which overcomes these limitations. The research objectives of this project are to expand the capability of these luminescent probes, as well as scale-up in order to provide enough material to meet manufacturing needs for initial product sales. By the end of the project, we will have reagents for performing site directed time-resolved measurements in live cells and an operational prototype time-resolved imaging module.

The broader impact/commercial potential of this project, if successful, is the potential to develop a new class of cell imaging reagents and techniques. This innovation will improve the ability of researchers to follow protein-protein interaction pathways with quantitative accuracy that has not been available before. This will impact not only fundamental and applied research but also primary healthcare through the discovery of novel pharmaceutical targets and mechanisms to diagnose and treat disease. The design and use of novel probes to study structure and function at the molecular and subcellular level in living cells is a topic of great importance, with a growing need for new approaches and tools to visualize not only the distribution of molecular species in cells, but the manner in which they interact. Protein-protein interactions and other dynamic events within cells have been largely invisible, but will be increasingly observable with new imaging modalities. In particular, lanthanide probes, with the dramatic lowering of background achieved through time-gating can enable new microscopic imaging, if successfully coupled with cell penetration and molecular targeting and recognition. This new scientific capability is certain to have significant commercial appeal and adoption in the basic science and medical research markets.

Agency: National Science Foundation | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 150.00K | Year: 2010

This Small Business Innovative Research Phase I Project will link analogs of Lumi4

Lumiphore, Inc. | Date: 2011-04-06

The invention provides compositions and methods useful in DNA sequencing. In exemplary embodiments, a detectable label such as a luminescent macrocycle is used.

Agency: NSF | Branch: Standard Grant | Program: | Phase: SMALL BUSINESS PHASE II | Award Amount: 899.31K | Year: 2014

This Small Business Innovation Research (SBIR) Phase II project proposes to develop novel caged macrocyclic chelating groups that display faster and more stable binding as compared to acyclic and mono-macrocyclic chelators currently used. Metallic radioisotopes offer versatile imaging and therapeutic properties, but loss of metallic radioisotopes from their site-directing molecules can lead to deleterious side-effects or reduced contrast and efficacy. There is a recognized, compelling need for improved chelating groups for use in radiopharmaceuticals. Such chelating groups must rapidly bind radioisotopes, so that they are compatible with the practicalities of clinical laboratory preparation. They must also stably bind the cation so that none is released in vivo, at least prior to its decay. The optimized chelating groups to be developed under this project will stably coordinate metal cations currently used for radioisotope-based diagnosis and therapy, display facile complexation kinetics, and provide a convenient synthetic handle for attachment to targeting moieties. By means of this approach, the novel chelators will both improve the utility of existing radiopharmaceuticals and permit the use of radionuclides that are at present underdeveloped in the clinic.

The broader impact/commercial potential of this project, if successful, will be that aromatic macrocyclic bifunctional chelators (AMBFCs) will be developed that will potentially change the landscape in the way cancer is detected and treated. Because the AMBFCs can be used in cancer imaging, the physician benefits from an effective feedback loop on therapeutic progress, remission, and prognosis that could further shorten the time of treatment. AMBFCs in companion radiodiagnostics also could reduce the cost of ineffectual medication, which is a strategic goal of the FDA. Plus, by employing novel radionuclides in the AMBFCs to kill tumors and their metastases, the benefit could materially cut down the time and cost of therapy. All of these features could promote better clinical outcomes and reduce the overall cost of healthcare by saving lives with earlier intervention. Through improved clinical outcomes from this unique science, AMBFCs will advance the national health, prosperity and welfare of others.

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