Nucleotide analogs
Inventors
Hostetler, Karl Y. • Beadle, James R. • Valiaeva, Nadejda
Assignees
US Department of Veterans Affairs • University of California San Diego UCSD
Publication Number
US-12350274-B2
Publication Date
2025-07-08
Expiration Date
2035-09-15
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Abstract
Disclosed herein, inter alia, are acyclic nucleotide analogs and methods of using an acyclic nucleotide analog for treating and/or ameliorating a papillomavirus infection.
Core Innovation
The invention discloses acyclic nucleotide analogs, specifically compounds of Formula (I), pharmaceutical compositions containing these compounds, processes for their synthesis, and methods of treating diseases, particularly viral infections caused by papillomaviruses. The compounds selectively inhibit viral DNA synthesis and production of virions of high-risk human papillomavirus (HPV) types without significant antiproliferative effects on host cells. This antiviral activity targets the replication mechanism of HPV to eradicate infection before precancerous cellular changes occur.
The problem addressed by the invention is the lack of approved antiviral treatments for early HPV infections that have not progressed to cancer. HPV is known to cause various warts and cancers, including cervical cancer, and current vaccines are only effective if administered before HPV exposure. Existing antiviral nucleoside or nucleotide analogs are poorly absorbed orally, limiting their clinical use. The invention provides new acyclic nucleotide analogs that overcome these limitations, offering selective inhibition of HPV replication and a potential early treatment option.
Claims Coverage
The patent contains one independent claim that defines a compound with a specified chemical structure featuring inventive moieties.
Compound structure with defined substituents targeting papillomavirus
A compound of Formula (I) having a bicyclic base structure (B1) and variable substituents Z1, Z2, R1, R2 that can be independently oxygen or nitrogen atoms, alkyl, alkenyl, aryl or heteroaryl groups, or forming cyclic moieties with the phosphorus atom, designed to inhibit viral DNA synthesis selectively.
The claim covers a class of nucleotide analog compounds characterized by specific chemical groups and linkages that enable selective inhibition of HPV DNA replication, constituting the core inventive feature of the patent.
Stated Advantages
Selective inhibition of viral DNA synthesis of high-risk HPV types without significant antiproliferative effects on host cells.
Potential to eradicate HPV infection before progression to invasive cancer.
Improved oral bioavailability and stability through the presence of moieties that neutralize phosphonate charge.
Sustained and extended efficacy due to resistance to in vivo degradation.
Documented Applications
Treatment and/or amelioration of papillomavirus infections in subjects, including both high-risk and low-risk HPV types such as HPV-16, HPV-18, HPV-6, and HPV-11.
Use in pharmaceutical formulations suitable for various administration routes including topical, oral, intravaginal, and targeted delivery systems.
Methods for treating human papillomavirus infection by administering an effective amount of the compound to inhibit viral replication and synthesis of viral DNA.
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