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Transcript
Licensing Opportunity Project #1415 Application of a Novel Protein Therapeutic Discovery Platform in Cancer Research The Advantages The Invention: The unique features of these proteins include our ability to optimize the protein sequence to promote binding to a given DNA target sequence creating sequence specificity and binding affinity –resulting in a platform technology. The current invention comprises a unique platform technology used to create highly specific DNA-binding proteins (MHP’s). The technology specifically enables researchers to develop highly efficacious therapeutic compounds that are both selective and competitive in terms of binding affinity. The proteins are based on naturally occurring homo- or hetero-dimer structures that incorporate novel functional design elements that include 1) a DNA-binding region derived from bHLH sequences, 2) a flexible ‘hinge’ region used to optimize the orientation of the binding regions and 3) structural tail units used to provide stability and define whether the protein subunits engage in homo or heterodimerization. These structural units may include leucine zipper dimerization domain from bZIP proteins or other similar leucine zipper sequences. A key feature of this platform technology centres on the programmable nature of the relevant binding and structural sequences of the proteins, which are optimized through a mutagenic evolution to target, with high affinity, specific DNA binding regions with known therapeutic potential. In addition, the resulting proteins are small, welldefined, helical structure of 25-60 amino acids ("minimalist") which have stable and easily characterized protein sequences that can be synthesized at low cost In addition the proteins are based on a small, well-defined, helical structure of 25-60 amino acids providing a stable ("minimalist") protein scaffold that can be synthesized chemically and at low cost Patent Status Two Patents are filed: 1. A U.S Patent Application No.: 11/442,310 entitled: “Minimalist bZIP derivatives that bind to non-canonical gene regulatory sequences” was filed with the US Patent and Trademark Office on May 30, 2007 and is still in prosecution. 2. A U.S Patent Application No. 11/592,186 entitled: “Minimalist bZIP Proteins and Uses Thereof” was filed with the USPTO on November 3, 2007 and has since been granted. Every precaution has been taken to ensure that the information presented in this document is accurate at the time of going to press. However, the University of Toronto makes no warranty or representation, expressed or implied, with respect to accuracy, completeness or usefulness of the information presented in this document. The Business Opportunity: Novel diagnostic and therapeutic strategies are urgently needed to improve the survival and treatment of cancer patients. This would significantly impact patient care, quality of life, and minimize human loss. To fill this gap, our goal is to develop minimalist hybrid protein (MHP) inhibitors to disrupt specific protein:DNA interactions contributing to human disease, including cancer and thereby developing a new class of cancer drugs. Specifically, we aim to develop the MHP platform to inhibit Myc/Max interaction with its E-box DNA-binding site. The Myc/Max heterodimer is a transcriptional regulator involved in the etiology of >50% of human cancers and hence is a pivotal target in the molecular control of tumour progression. The Challenge: In order to demonstrate and validate the efficacy of these proteins in model systems, proprietary delivery systems must be developed and tested. We have currently assembled a team to accomplish all of these goals and overcome this barrier. Efficient tumour cell delivery of MHPs will be achieved through the development of novel non-toxic Nano-MHPs, sub-100 nm metal nanocrystals that will be coated with these small inhibitor proteins to develop a targeting vehicle. MHP target validation will be conducted at the level of Myc/Max gene transcription using chromatin immunoprecipitation (ChIP) technologies in tumour cells. Team: The members of the MHP team possess unique expertise necessary to commercialize this technology. The contribution of each PI’s research efforts to our MHP team will be (1) the generation and optimization of small protein therapeutics (Dr. Jumi Shin), (2) integration of a nanodelivery system (Dr. Warren Chan), and (3) quantitative data on MHPs' inhibitory capabilities including models and assays for myc (Dr. Linda Penn). We are now positioned to use our platform to test our current portfolio of MHPs known to disrupt Myc/Max binding to the E-box, to suppress the proliferation of tumour cells, and ultimately for the basis of a therapy that will improve patient outcomes. Contact: Partnering Opportunity: Ian Stewart, PhD, MBA Senior Manager, Life Sciences The Innovations & Partnerships Office We are seeking industry partners to help us develop this technology and ultimately license the inventions. Specifically, we will use our platform for the rational design and selection/directed evolution to identify and select short MHP’s lead candidates that block the Myc/Max:E-box interaction, validate our nanotech vehicle to deliver the MHP into the nucleus of mammalian cells and evaluate the efficacy of Nano-MHPs to block tumourigenesis of human cancer cells and inhibit Myc binding to E-box DNA in tumour cells. Phone: (416) 946-7734 Email: [email protected] Every precaution has been taken to ensure that the information presented in this document is accurate at the time of going to press. However, the University of Toronto makes no warranty or representation, expressed or implied, with respect to accuracy, completeness or usefulness of the information presented in this document.