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Code · REGISTER · 2024-04-05 · National Institutes of Health, HHS · Notices

Notices. Notice

573 words·~3 min read·/register/2024/04/05/2024-07278·

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BILLING CODE 4140-01-P DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health 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; *michael.shmilovich@nih.gov,* 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A signed Confidential Disclosure Agreement may be required to receive any unpublished information.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: EN05AP24.048 Where L is optionally present and is a C <sup>1</sup> -C <sup>6</sup> alkyl group, a C <sup>1</sup> -C <sup>6</sup> alkoxy group, a -(CH <sup>2</sup> CH <sup>2</sup> O) <sup>n</sup> - 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 <sup>1</sup> is S(=O) or S; Y <sup>1</sup> is N or CR <sup>4</sup> ; and each of R <sup>1</sup> -R <sup>7</sup> is independently selected from hydrogen, C <sup>1</sup> -C <sup>6</sup> alkyl, C <sup>1</sup> -C <sup>6</sup> alkoxy, perfluoro C <sup>1</sup> -C <sup>6</sup> alkyl, perfluoro C <sup>1</sup> -C <sup>6</sup> alkoxy, halo, -CN, -OH, -COOR <sup>8</sup> , substituted or unsubstituted aromatic, or substituted or unsubstituted heteroaromatic, and each R <sup>8</sup> independently is hydrogen, C <sup>1</sup> -C <sup>6</sup> 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; *michael.shmilovich@nih.gov.* Dated: April 2, 2024. Michael A. Shmilovich, Senior Licensing and Patenting Manager, National Heart, Lung, and Blood Institute, Office of Technology Transfer and Development. [FR Doc. 2024-07278 Filed 4-4-24; 8:45 am]
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