# Government-Owned Inventions; Availability for Licensing
**AGENCY:**
National Institutes of Health, HHS.
**ACTION:**
Notice.
**SUMMARY:**
The inventions listed below are owned by an agency of the U.S. Government and are available for licensing in the U.S. to achieve expeditious commercialization of results of federally-funded research and development.
**FOR FURTHER INFORMATION CONTACT:**
Licensing information may be obtained by contacting Michael Shmilovich, Esq, MS, CLP; 301-435-5019; *[email protected],* at the National Heart, Lung, and Blood, Office of Technology Transfer and Development Office of Technology Transfer, 31 Center Drive Room 4A29, MSC2479, Bethesda, MD 20892-2479. A signed Confidential Disclosure Agreement may be required to receive any unpublished information.
**SUPPLEMENTARY INFORMATION:**
This notice is in accordance with 35 U.S.C. 209 and 37 CFR part 404. Technology description follows. Prazole-Based Antiviral Therapeutics:
Available for licensing and commercial development is a patent estate that covers prazole based compounds and their methods of use as antiviral therapeutics. Prazoles are benzimidazole derivatives generally marketed as stomach-acid reducers, owing to their ability to inhibit the H+/K+ ATPases (proton pumps) of the parietal cells in the stomach epithelium. Prazoles can inhibit the egress of several viral targets: HIV-1, HSV-1 and -2, MAYV, and EBV by interfering with the ESCRT complex in the formation of exosomes. In that respect, the target for inhibition of these viruses is Tumor susceptibility gene 101 (Tsg101), a member of the ESCRT-I complex. The N-terminal ubiquitin E2 variant (UEV) domain of Tsg101 has both ubiquitin and P[T/S]AP motif binding sites, where the prazole binds to C73 in the middle of the ubiquitin-binding site, sterically inhibiting the Ub-Tsg101 interaction. By way of example, and not limitation, a prazole compound according to this invention can take on the follow core structure:
Where L is optionally present and is a C <sub>1</sub> -C <sub>6</sub> alkyl group, a C <sub>1</sub> -C <sub>6</sub> alkoxy group, a -(CH <sub>2</sub> CH <sub>2</sub> O) <sub>n</sub> - group where n is an integer from 1 to 6, a phenyl group, or a benzyl group, each of which is optionally substituted. B is a substituted or unsubstituted aromatic or heteroaromatic substituent, and where
X <sub>1</sub> is S(=O) or S;
Y <sub>1</sub> is N or CR <sub>4</sub> ; and
each of R <sub>1</sub> -R <sub>7</sub> is independently selected from hydrogen, C <sub>1</sub> -C <sub>6</sub> alkyl, C <sub>1</sub> -C <sub>6</sub> alkoxy, perfluoro C <sub>1</sub> -C <sub>6</sub> alkyl, perfluoro C <sub>1</sub> -C <sub>6</sub> alkoxy, halo, -CN, -OH, -COOR <sub>8</sub> , substituted or unsubstituted aromatic, or substituted or unsubstituted heteroaromatic, and
each R <sub>8</sub> independently is hydrogen, C <sub>1</sub> -C <sub>6</sub> alkyl, phenyl, or benzyl.
*Potential Commercial Applications:*
• antivirals
• therapeutics
• ESCRT complex formation
• prazole
• antifungal
*Development Stage:*
• Early stage
*Inventors:* Nico Tjandra (NHLBI), Carol Carter (Stonybrook), Rolf E. Swenson (NHLBI), David Nyenhuis (NHLBI), Natarajan Raju (NHLBI), Chandra Mushti, (NHLBI), and Venkata Sabbasani (NHLBI).
*Intellectual Property:* HHS Reference No. E-239-2023-0; U.S. Provisional Patent Application No. 63/545,080 filed October 20, 2023.
*Publication:* D. A. Nyenhuis, S. Watanabe, R. Bernstein, R. E. Swenson, N. Raju, V. R. Sabbasani, C. Mushti, D.-Y. Lee, C. Carter, N. Tjandra, “Structural Relationships to Efficacy for Prazole-Derived Antivirals.” *Adv. Sci.* 2024, 2308312. *https://doi.org/10.1002/advs.202308312.*
*Licensing Contact:* Michael Shmilovich, Esq, MS, CLP; 301-435-5019; *[email protected].*
Dated: April 2, 2024.
Michael A. Shmilovich,
Senior Licensing and Patenting Manager, National Heart, Lung, and Blood Institute, Office of Technology Transfer and Development.