Combinations of inhibitors of influenza virus replication
Inventors
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Assignees
MemberCocrystal PharmaCocrystal PharmaCocrystal Pharma is a clinical-stage biotechnology company specializing in the discovery and development of novel antiviral therapeutics for serious and chronic viral diseases such as influenza, COVID-19, hepatitis C, norovirus, and other respiratory viruses. The company leverages structure-based drug discovery technology and expertise in structural biology to design direct viral replication inhibitors with broad-spectrum activity. Its pipeline includes candidates in preclinical and clinical development, addressing unmet needs in antiviral medicine.
Cocrystal Pharma is a clinical-stage biotechnology company specializing in the discovery and development of novel antiviral therapeutics for serious and chronic viral diseases such as influenza, COVID-19, hepatitis C, norovirus, and other respiratory viruses. The company leverages structure-based drug discovery technology and expertise in structural biology to design direct viral replication inhibitors with broad-spectrum activity. Its pipeline includes candidates in preclinical and clinical development, addressing unmet needs in antiviral medicine.
Publication Number
US-12233066-B2
Publication Date
2025-02-25
Expiration Date
Abstract
Provided herein are combinations of compounds that can inhibit the replication of influenza viruses, reduce the amount of influenza viruses, and/or treat influenza.
Core Innovation
The invention relates to influenza virus replication-inhibiting combination therapies centered on administering 3-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[2.2.2]octane-2-carboxylic acid, or a pharmaceutically acceptable salt or solvate, together with a second antiviral agent selected from baloxavir marboxil, baloxavir, oseltamivir, oseltamivir acid, and favipiravir, or a pharmaceutically acceptable salt or solvate. The approach is directed to treating influenza virus infection or reducing influenza virus replication in a subject in need thereof.
The patent describes a target rationale in which the bicyclo[2.2.2]octane-2-carboxylic acid acts as a CAP-binding PB2 inhibitor and relates to influenza polymerase cap-snatching endonuclease, while the second antiviral agent is selected from neuraminidase inhibitors and baloxavir or favipiravir. Combination administration is described as therapeutically effective for influenza A and influenza B, including in contexts such as pandemic and drug-resistant strains, with treatment or prophylactic use.
The described combination therapy includes options for timing and formulation, including co-administration at the same time or by administering the bicyclic carboxylic acid before or after the second antiviral agent, and with options for co-formulated administration versus separately administered formulations. The patent further describes use of the combination in humans, including patients having or at risk of influenza infection.
Claims Coverage
The document includes three independent claims. Across these claims, five principal inventive elements are present: the specified bicyclo[2.2.2]octane-2-carboxylic acid scaffold, co-administration with a defined second antiviral agent set, treating or reducing influenza virus replication, a human patient dose range, and the combination format itself.
Influenza treatment by administering CAP-binding PB2 inhibitor with second antiviral
A method of treating influenza virus infection or reducing influenza virus replication in a subject in need thereof comprising administering to the subject a therapeutically effective amount of 3-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[2.2.2]octane-2-carboxylic acid, or a pharmaceutically acceptable salt or solvate thereof, and a second antiviral agent selected from baloxavir marboxil, baloxavir, oseltamivir, oseltamivir acid, and favipiravir, or a pharmaceutically acceptable salt or solvate thereof.
Human patient treatment with specified bicyclic dose and second antiviral selection
A method for treating influenza virus infection or replication, comprising administering to a human patient having or at risk of influenza infection 3-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[2.2.2]octane-2-carboxylic acid, or a pharmaceutically acceptable salt or solvate thereof, in a dose of about 10-1,000 mg/kg and a therapeutically effective amount of a second antiviral agent selected from baloxavir marboxil, baloxavir, oseltamivir, oseltamivir acid, and favipiravir, or a pharmaceutically acceptable salt or solvate thereof.
Combination comprising bicyclic carboxylic acid and second antiviral agent
A combination comprising 3-(2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)bicyclo[2.2.2]octane-2-carboxylic acid, or a pharmaceutically acceptable salt or solvate thereof, and a second antiviral agent selected from baloxavir marboxil, baloxavir, oseltamivir, oseltamivir acid, and favipiravir, or a pharmaceutically acceptable salt or solvate thereof.
Across the independent claims, the coverage centers on influenza virus replication-inhibiting therapy that combines a specified bicyclo[2.2.2]octane-2-carboxylic acid with a second antiviral agent selected from baloxavir marboxil/baloxavir, oseltamivir/oseltamivir acid, or favipiravir, with one independent claim additionally limiting use in a human patient context and specifying a dose range for the bicyclic component.
Stated Advantages
Strong synergism between the specified compound and baloxavir, oseltamivir acid, and favipiravir against influenza A/PR/8/34 (H1N1), as reported using MacSynergy II with Cytopathic Effect (CPE) assay data.
Antiviral activity extending to influenza B.
Documented Applications
Treating influenza virus infection or reducing influenza virus replication in a subject in need thereof.
Treating influenza virus infection or replication in a human patient having or at risk of influenza infection.
Treating an Influenza A or Influenza B infection in a host by administering a therapeutically effective amount of the combination to reduce influenza polymerase endonuclease activity and/or reduce influenza virus replication.
Optionally administering an additional third antiviral agent to a host in an influenza context.
Optionally administering an influenza vaccine to the host before, after, or concurrently with the combination.
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