IN COMPROMISED HEARTS, muscle contractions are weakened as the protein motor myosin binds too tightly to its regulator MyBP-C. Richard L. Moss , the Senior Associate Dean for Basic Research, Biotechnology and Graduate Studies at the University of Wisconsin School of Medicine, in collaboration with Ariel Fernandez Stigliano, the discoverer of the dehydron (脱水元), invented a drug that disrupts this protein association, releasing the “molecular brakes” that cause heart failure. This invention constitutes the first molecularly targeted treatment of heart failure based on rational design. The molecular physiology that led to the discovery was elucidated by Richard L. Moss, while the underlying science behind the novel molecular design is described in Ariel Fernandez’s book “Biomolecular Interfaces: Interactions, Functions and Drug Design“, with a foreword by the co-inventor in the patent. The activities of Prof. Ariel Fernandez at the University of Wisconsin-Madison (Morgridge Institute for Resarch) enabled this collaboration that ultimately led to the invention. The patent assignee is the Wisconsin Alumni Research Foundation (WARF P120252US02).
You may read the press release for Richard Moss and Ariel Fernandez’ patent US9051387 featured in Yahoo, MarketWatch. in the original form submitted by Ariel Fernandez Consultancy to PR NewsWire, or prior to distribution in WebWire. There is also a video by Ariel Fernandez covering the science behind the invention.
Ariel Fernandez Consultancy serves the biotechnology industry by harnessing fundamental discoveries to broaden its technological base. In line with this goal, Richard L. Moss in collaboration with Ariel Fernandez invented a new drug for the molecular targeted treatment of heart failure. The invention named “Inhibition of MYBP-C binding to myosin as a Treatment for Heart Failure” was awarded the US patent 9,051,387 on June 9, 2015.
The recently awarded US patent number 9051387 describes the first therapeutic disruption of a protein-protein association using a rationally designed man-made ligand, a challenge considered to be the holy grail in drug discovery (see Nature review by James Wells et al.). At the molecular level, the effect of the drug is the disruption of the association between the molecular motor myosin and its modulator MYBP-C by a competitive man-made ligand that binds to MYBP-C. The target was identified by Richard L. Moss, who also conducted the experimental tests, while the drug itself was created by Ariel Fernandez based on his translational ideas on rational design.
The basic scheme descriptive of the molecular action of the invention is shown in the following figure:
The main difficulty in designing the myosin-MYBP-C disruptor is that the 3D-structure of the target MYBP-C is not known. Thus the binding site had to be inferred by detecting regions of the protein in the twilight between order and disorder, using exactly the same methodology developed by Ariel Fernandez in Nature 474, 502-505 (2011).
This invention is featured at: US Patent and Trademark Office page, Espacenet page, Description by the University of Wisconsin-Madison, Ariel Fernandez Consultancy, Academia.edu, Ariel Fernandez’s professional page. This patent marks the dawn of the new paradigm for drug discovery based on epistructural biology, the new discipline introduced by Ariel Fernandez in the latest book Biomolecular Interfaces (Springer, Berlin, 2015).