Methods of treating retroviral infections and related dosage regimes

Inventors

Lanier, Ernest Randall

Assignees

Chimerix Inc

Abstract

The present invention relates to compounds and methods for treating retroviral infections and/or Hepatitis B viral infections. Some compounds of the invention are described by Formula I:or a stereoisomer, a diastereomer, an enantiomer or racemate thereof.

Core Innovation

The disclosed subject matter describes treating or preventing retroviral infections, including HIV and XMRV, and treating hepatitis B virus (HBV) infections in a primate subject. The approach administers a therapeutically effective amount of phosphonate ester tenofovir derivatives, including compounds of Formula I and their stereoisomers, diastereomers, enantiomers, and racemates, or pharmaceutically acceptable salts thereof.

The disclosure provides pharmaceutically acceptable salt and cation scope for the tenofovir derivatives, including M+ cations such as K+, Na+, Li+, Ca2+, Mg2+, and N-containing ammonium-type cations, together with daily or weekly administration. It states that increasing intracellular tenofovir-diphosphate (TFV-PP) levels compared to tenofovir is associated with potency against drug-resistant HIV and activity against XMRV.

The disclosure discusses possible mechanisms and supporting pharmacokinetic/pharmacodynamic claims, including viral binding and uptake into privileged compartments such as CNS, seminal, lymphoid, and testes. It also discusses transporter-related findings, including that tenofovir is an OAT1 substrate while CMX157 is not, and it indicates that this is associated with a lower OAT-mediated nephrotoxicity risk.

Claims Coverage

The partial claim set includes two independent claims directed to methods for treating HBV infection in a primate subject, each based on administering a therapeutically effective amount of a specified tenofovir-derivative compound or its pharmaceutically acceptable salt, with administration daily or weekly in an amount of about 25 mg to about 2000 mg. The independent claims differ in how the compound is defined: one recites the compound structure generally, and the other recites the formula and salt cation definition (M+).

Across the independent claims, the claimed HBV treatment is grounded on daily or weekly administration of a therapeutically effective amount (about 25 mg to about 2000 mg) of a phosphonate ester tenofovir derivative either defined by its structure or defined by an M+ pharmaceutically acceptable salt formula compound with R1–R4 hydrogen or C1-5 alkyl.

Stated Advantages

Documented Applications