A That Does Not Reactivate Category as Problem: Varicella zoster (VZV) causes varicella () in 4 million children Zoster (Shingles) Vaccine yearly. After varicella, VZV becomes latent but can spontaneously reactivate decades later resulting in zoster (shingles), which is characterized by pain and rash. Such reactivation is Problem especially problematic in elderly or immunocompromised patients and can lead to a variety Current shingles of complications such as (chronic pain), stroke, paralysis, and can reactivate and do not blindness. Although the Zostavax reduces the incidence of shingles by 51%, induce strong immune even if every person more than 60 years old were vaccinated, there would still be at least responses 500,000 patients annually. The oka vaccine virus reactivates asymptomatically and other candidate shingles vaccines do not produce a strong immune response. There is a need for Technology Overview a vaccine that induces a long-lasting immunity and will not reactivate to cause shingles. as Shingles vaccines that Solution: Researchers from the contain mutated University of Colorado have that only replicate under developed mutated viral strains defined conditions that only replicate under defined

conditions and can be used as IP Status shingles vaccines. The inventors  US Patent Issued found that ORF 63 or 70 protein  Available for Exclusive expression is required for varicella or Non-Exclusive virus replication. They used a Figure 1. Effect of TMP on the replication of SVV mutant is Licensing rhesus macaques model to develop reversible. SVV mutant-infected cells were cultured with 100nM mutant viral strains as the primate TMP. Active virus replication was confirmed by GFP expression. Advantages version of VZV, simian varicella After TMP removal minimal GFP was detected.  Prevents zoster virus (SVV), closely parallels VZV infection in humans. They developed a SVV mutant in which reactivation ORF 63 is deleted and ORF 70 is fused to a destabilization domain. Upon translation, the ORF  Protects elderly and 70 protein is typically degraded in this mutant, but in the presence of the antibiotic immunocompromised trimethoprim (TMP), it is stable and promotes virus replication. The ability of TMP to drive individuals susceptible SVV mutant replication in a reversible manner, meaning that after TMP removal the virus to complications stop replicating, is shown in Figure 1. These results suggest that a vaccine comprising of  Prevents conditions conditional SVV or analogous VZV mutants administered with the antibiotic TMP will elicit a cause by reactivation protective immune response against the virus but that replication of the virus can be

reversibly completely “turned off” by the removal of the antibiotic. Contact James Parrett Advantages and Value Propositions [email protected] Each year, 600,000 to 1 million Americans are affected by shingles. The most common Ref#CU3061H complication, postherpetic neuralgia, develops in 200,000 - 300,000 Americans per year. By 2023, the shingles treatment market is expected to register a CAGR of 13.48%. The CU Innovations conditional mutants described here can be used as vaccines that produce good immune 303-724-0221 responses but do not reactivate to produce zoster. This will help prevent conditions such as [email protected] postherpetic neuralgia that can develop after shingles and is especially valuable to individuals of advanced age with who are more susceptible to such complications. Additional Documents and Sources: “Conditional Replication Deficient Varicella Zoster Viral Strains and use Thereof in Vaccines.” U.S. Patent No. 10,232,035 issued March 19, 2019.

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