Nucleotide analogs

Inventors

Hostetler, Karl Y.Beadle, James R.Valiaeva, Nadejda

Assignees

US Department of Veterans AffairsOffice of General Counsel of VAUniversity of California San Diego UCSD

Publication Number

US-10702532-B2

Publication Date

2020-07-07

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 and methods of using these analogs for treating and/or ameliorating papillomavirus infections. Specifically, the invention includes antiviral agents that selectively inhibit and/or block viral DNA synthesis and/or the production of virions of high-risk human papillomavirus (HPV) types, thereby eradicating the infection before cellular changes lead to invasive cancers.

The problem being addressed is the lack of approved antiviral treatments for human papillomavirus infections, especially for early HPV infections that have not progressed to cancer. Papillomaviruses cause conditions ranging from warts to cancers such as cervical, vaginal, anal, and oropharyngeal cancers. Existing HPV vaccines provide limited benefit after infection, and current antiviral nucleoside or nucleotide analogs have limitations such as poor oral bioavailability or toxicity.

Claims Coverage

The patent claims encompass one independent method claim directed to treating human papillomavirus infection via administration of a specific compound. The main inventive feature involves the compound's use and administration methods for treating HPV.

Method for treating human papillomavirus infection

A method for the treatment of human papillomavirus in a human in need thereof, comprising administering an effective amount of a specified acyclic nucleotide analog compound of a defined chemical structure to inhibit viral replication by inhibiting viral DNA synthesis.

Administration methods of the compound

The compound can be administered topically and formulated as a cream, gel, suppository, or vaginal ring for effective treatment of HPV infection.

Targeting specific HPV types

The method includes treatment of specific HPV types, including HPV-16, HPV-18, HPV-52, and HPV-58, covering both high-risk and low-risk HPV strains.

The claims focus on the use of novel acyclic nucleotide analog compounds for treating HPV infections via various administration routes, targeting specific HPV types, and inhibiting viral DNA replication, representing a selective antiviral approach.

Stated Advantages

The invention provides antiviral activity against papillomavirus by selectively inhibiting viral DNA synthesis without significant antiproliferative effects on host cells.

The compounds can eradicate HPV infection before cellular changes lead to invasive cancers.

The presence of moieties that neutralize phosphonate charge improves cell membrane penetration, oral bioavailability, aqueous stability, and reduces byproduct-related toxicity compared to prior analogs.

Compounds can be metabolized to active diphosphate forms acting as chain terminators of DNA synthesis, thus blocking viral replication.

Documented Applications

Treatment or amelioration of human papillomavirus infection, including both high-risk HPV types (such as HPV-16, HPV-18, HPV-31, HPV-33, HPV-35, HPV-39, HPV-45, HPV-51, HPV-52, HPV-56, HPV-58, HPV-59, HPV-68, HPV-73, HPV-82) and low-risk types (such as HPV-6 and HPV-11).

Use in pharmaceutical compositions for preventing or treating viral infections caused by papillomaviruses.

Topical applications such as creams, gels, suppositories, and intravaginal rings for localized delivery against HPV infections.

Potential use in combination therapy with other agents to treat papillomavirus infection.

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