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 C₁ -C₆ alkyl group, a C₁ -C₆ alkoxy group, a -(CH₂ CH₂ O)_n - 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

X₁ is S(=O) or S;

Y₁ is N or CR₄; and

each of R₁ -R₇ is independently selected from hydrogen, C₁ -C₆ alkyl, C₁ -C₆ alkoxy, perfluoro C₁ -C₆ alkyl, perfluoro C₁ -C₆ alkoxy, halo, -CN, -OH, -COOR₈, substituted or unsubstituted aromatic, or substituted or unsubstituted heteroaromatic, and

each R₈ independently is hydrogen, C₁ -C₆ 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.

89 FR 24023