Read this short Q&A with IPD Director Dr. David Baker on the recent Cell publication entitled A computationally designed inhibitor of an Epstein-Barr viral Bcl-2 protein induces apoptosis in infected cells.
Q: What is the IP status of your findings?
A: A patent application has been filed for BINDI protein. Prior patents have been granted for earlier generation copolymer-based delivery vehicles that cover aspects of the intracellular delivery agents used in this study.
Q: What is the licensing status of your work?
A: We have not yet thought about how the BINDI protein would be licensed. The main reason for patent protection is to help protect later generation variants that we are creating to specifically bind all endogenous human BCL-2 family members. These protein variants may be useful in characterizing BCL2-dependency of different cancers, and might be useful therapeutics in a range of cancers if delivered intracellularly. Epsetin-Barr virus (EBV)-positive Burkitt’s lymphoma is rare in the Western world, and is mostly found in areas with endemic malaria, especially equatorial Africa. It is an extremely fast-growing cancer, but that also makes it quite susceptible to current chemotherapies. Hence while BINDI nicely demonstrates the principle of delivering a specific toxin to cancer cells, it is likely in the future that other specific toxins targeting alternative cancer types will find a wider market.
Q: Are there any companies involved with this or future work?
A: Yes. Patrick Stayton (UW) and Oliver Press (FHCRC and UW) who are co-authors on this paper, together with three others, co-founded the company PhaseRx. This company uses copolymer-based micelle carriers to deliver RNA inside target cells, in particular liver cancer. The polymeric carriers combined with the antibody-targeting that we used in our manuscript are exciting advances because we now deliver proteins intracellularly.
Q: What next steps will you be undertaking in order to use BINDI to treat Epstein-Barr virus-associated cancers? Are your first goals to optimize the dosing, the targeting, and the carrier to increase therapeutic efficacy of BINDI?
A: BINDI is already spectacularly tight and specific amongst BCL-2 family members. Whether it inadvertently binds other cellular proteins to cause unwanted toxicity, we do not know. Were we to improve BINDI, we would make it catalytic (i.e. a protease to destroy EBV BHRF1), but our efforts are instead focused on creating other specific BCL-2 family binders (see comments to second question above). In regards to the micelle carrier, there is much room for optimization. This includes optimizing dosing, finding the ideal antibody for receptor-mediated endocytosis, finding the optimum chemical attachment between the copolymer and antibody or payload, and varying the composition and lengths of the copolymer blocks. Many of these experiments are done in mice and therefore take a significant amount of time. Patrick Stayton and Geoffrey Berguig have a manuscript in submission describing some of these ongoing experiments.
Q: Do you have any other comments on the implications on these findings that you would like to share?
A: Computationally designing proteins with desired functions is going to change the face of biotechnology, and open the door to a whole new world of biopharmaceuticals.
The BINDI protein was designed in the laboratory of Dr. David Baker who is the Director of the Institute for Protein Design , a highly collaborative organization operated within the School of Medicine at the University of Washington, and linked to numerous Seattle area collaborating researchers. The goal of the IPD is to design a whole new world of synthetic proteins that address 21st century challenges in medicine, energy, and technology.
To further develop new protein designs like BINDI to the point that they can be commercialized or form the basis for new startup companies , the IPD has established a Translational Research Center supported in part by a $1.4M Opportunity Grant Award from the Life Sciences Discovery Fund, and ~$5.2 M in generous matching fund support from the UW (both the President and the School of Medicine), local philanthropists, and the Washington Research Foundation.
The IPD has established tightly woven interdisciplinary collaborations like that reported in the Cell paper, to produce, test, and validate new protein designs for vaccines, therapeutics, diagnostics, enzymes, nanomaterials, and clean energy. Our collaborative efforts have recently been enhanced with an $8M gift from the Washington Research Foundation (WRF) for the WRF-IPD Innovation Fellows program supporting talented postdoctoral fellows who will learn, improve and apply protein design methods in collaboration with local partner institutes. Additional funding for the IPD has come from Governor Jay Inslee’s 2014 Supplemental Budget (4-13-14) which included $1 million for the Institute for Protein Design.