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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.