Mayo Patent Watch: Fighting Cancer, Autoimmune Disease With Bioengineered Viruses

Top researchers James Russell, Moses Rodriguez cited as inventors of virus tech platforms.

Mayo Patent Watch: Fighting Cancer, Autoimmune Disease With Bioengineered Viruses
The Mayo Foundation for Medical Education and Research, the nonprofit parent entity of the Mayo Clinic, is a worldwide research powerhouse that is assigned scores of U.S. patents each year. Mayo scientists and doctors are at the scientific forefront of many medical specialties, and the breadth of their activities is widely varied.
As part of its healthcare industry coverage, TCB is taking occasional looks at recent patents awarded to the Mayo Foundation and its inventors in a feature called Mayo Patent Watch. This installment of the series includes patents assigned to Mayo in late August 2016.

Patent No.: 9,428,736
Title: Vesicular Stomatitis Viruses
Inventor: Stephen J. Russell, M.D., Shruthi Naik
Dr. Stephen Russell, a professor of molecular medicine at Mayo Clinic and CEO of Rochester biotech start-up Vyriad, has made headlines over the last several years in connection with his efforts to harness the potential of bioengineered oncolytic viruses to attack cancer cells.
Among the most promising candidates are vesicular stomatitis viruses (VSVs). In nature, VSVs can be isolated from insects and livestock and are not considered human pathogens. However, they can be engineered to selectively replicate in tumor cells and destroy them without harming healthy cells.
Russell’s work is based on the demonstrated ability of such viruses to target and destroy cancer cells while also stimulating the body’s adaptive anti-tumor immune response to continue killing cancer cells. This anti-tumor immune response is more powerful when the virus has been bio-engineered to include a tumor antigen.
Russell’s now-patented VSV platform has been licensed by Mayo to his own spinoff company, Vyriad, which is a Mayo Clinic Ventures portfolio company and is housed in its Business Accelerator in downtown Rochester.
The company was originally known as Omnis Pharma. In January 2015 it signed a licensing deal with pharmaceutical giant AstraZeneca and its subsidiary MedImmune to study, improve and potentially commercialize Omnis’ VSV technology by pairing it with its own anti-cancer immunotherapy drug candidates. The idea is that by pairing engineered viruses with drugs that enhance the body’s natural immune response, the anti-cancer effect can be amplified.
In March, Omnis Pharma merged with another Rochester start-up, Magnis Therapeutics, to form Vyriad. It boasts a pipeline of eight oncolytic virotherapies in clinical trial phases and seven in late-stage pre-clinical development. The eight clinical products include Phase II candidates targeting ovarian cancer and multiple myeloma, as well as Phase I programs in glioblastoma, mesothelioma, head and neck cancer, blood cancers, endometrial cancer, hematologic malignancies, and gastrointestinal cancer.

Patent 9,421,242
Title: Methods and Materials for Reducing the Severity of Viral Infections
Inventors: Moses Rodriguez M.D., Allan Bieber, Arthur E. Warrington Jr., Meghan McGee-Lawrence, Eric Poeschla M.D.
This patent comes out of work performed at Mayo Clinic’s Center for Multiple Sclerosis and Autoimmune Neurology, headed by Dr. Moses Rodriguez, which is searching for cures to autoimmune diseases such as MS. More generally, they’re seeking nothing less than a broad-based vaccine that could function against all viruses in the world.
Mayo’s new patent relates specifically to the use of a bioengineered expression of a gene contained in the Theiler's Murine encephalomyelitis virus (TMEV), known as 3-D polymerase. The expression was engineered in connection with a project called Development of a Broad-Spectrum Antiviral Agent, which grew out of concern about the global health threat posed by viruses (such as could be used by bio-terrorists) for which there are no known pharmaceuticals.
Dr. Rodriguez's team of investigators recently discovered that 3-D polymerase used in inbred mice resulted in a mouse that is resistant to virus infections. These mice were able to withstand lethal doses of encephalomyocarditis virus, which causes fatal heart disease in humans, as well as infection with herpes viruses, which can cause a variety of disabling diseases in humans, including fatal encephalitis.
The mice also survived infection with vesicular stomatitis virus (see above patent), which is typically transmitted by insects and causes ulcers in the mouths of animals. They bred perfectly well in the laboratory and lived normal lifespans without diseases. Essentially, the mice are normal -- except for being highly resistant to virus infection.
Yet another promising result from the studies is that the subject mice don’t develop autoimmune diseases. The significance to human health in this work are potentially enormous – creating immunity either before or after exposure to potentially lethal virus infections as well as a cure for MS and other autoimmune diseases. 
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