Anti-bacterial compositions and uses thereof

Inventors

FEVRE, CINDY • BLOIS, Hélène • Medina, Mathieu

Assignees

Phaxiam Therapeutics SA

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Publication Number

US-11690885-B2

Patent

Publication Date

2023-07-04

Expiration Date


Abstract

The present invention relates to bacteriophage therapy. More particularly, the present invention relates to novel bacteriophages having a high specificity against Staphylococcus aureus strains, their manufacture, components thereof, compositions comprising the same and the uses thereof in phage therapy and as companion diagnostic.

Core Innovation

The patent describes bacteriophage therapy and antibacterial compositions for Staphylococcus aureus, including bacteriophages having lytic activity against at least one S. aureus strain. The antibacterial compositions include at least two distinct bacteriophages and a pharmaceutically acceptable excipient or carrier, and the phages are selected based on genome nucleotide sequence criteria of SEQ ID NOs: 1 to 4, or sequences having at least 95% identity thereto.

The disclosed scope includes embodiments for treatment and improvement of conditions in a human or animal by administering an antibacterial composition comprising lytic bacteriophages selected by SEQ ID sequence identity. It further includes decontaminating a material contaminated with an S. aureus strain by contacting the material with an antibacterial composition containing lytic bacteriophages selected by the SEQ ID NO: 1 to 4 or at least 95% identity rule, and modifying the microbial flora where the microbial flora comprises the S. aureus strain.

The patent also discloses selection and preparation concepts for bacteriophage cocktails. A method is provided for preparing an antibacterial composition by separately producing at least two lytic bacteriophages selected according to the SEQ ID NOs: 1 to 4 or sequences with at least 95% identity, and then combining the bacteriophages with a suitable carrier or excipient. A further method is provided for determining a cocktail of bacteriophages effective against a target S. aureus strain by separately contacting the target strain, or a sample containing it, with bacteriophages defined by the SEQ ID NOs, selecting bacteriophages that exhibit lytic activity, and optionally selecting combinations showing synergistic activity and/or exhibiting no antagonism, and optionally selecting bacteriophages belonging to different genus before combining the selected bacteriophages.

Claims Coverage

The partial claim set includes five independent claims directed to an antibacterial composition and several related uses and preparation/selection methods. The inventive features are centered on bacteriophages with lytic activity against S. aureus, selection by genome nucleotide sequence identity to SEQ ID NOs: 1 to 4, and the inclusion of formulation components including a preservative in the carrier for the composition claim.

Antibacterial composition with at least two distinct lytic bacteriophages selected by SEQ ID genome criteria

An antibacterial composition comprising at least two distinct bacteriophages having lytic activity against at least one Staphylococcus aureus strain and a pharmaceutically acceptable excipient or carrier, wherein the at least two bacteriophages are selected from bacteriophages having a genome comprising a nucleotide sequence of any one of SEQ ID NOs: 1 to 4 or a sequence having at least 95% identity thereto, and wherein the pharmaceutically acceptable excipient or carrier comprises a preservative in an amount effective to preserve the activity of the bacteriophages.

Treating an S. aureus infection by administering an antibacterial composition with SEQ ID genome-selected lytic bacteriophage(s)

A method of treating a Staphylococcus aureus infection in a human or animal in need thereof, comprising administering an antibacterial composition in an amount effective to treat the infection, wherein the antibacterial composition comprises at least one bacteriophage having lytic activity against at least the S. aureus strain and the at least one bacteriophage is selected from the bacteriophages having a genome comprising a nucleotide sequence of any one of SEQ ID NOs: 1 to 4 or a sequence having at least 95% identity thereto.

Modifying microbial flora to improve condition using lytic S. aureus phage(s) selected by SEQ ID genome criteria

A method of modifying the microbial flora in a human or animal to improve the condition, comprising administering an antibacterial composition in an amount effective to modify the microbial flora or to improve the condition, wherein the antibacterial composition comprises at least one bacteriophage having lytic activity against at least one Staphylococcus aureus strain, the at least one bacteriophage is selected from bacteriophages having a genome comprising a nucleotide sequence of any one of SEQ ID NOs: 1 to 4 or a sequence having at least 95% identity thereto, and wherein the microbial flora comprises the S. aureus strain.

Decontaminating a material contaminated with S. aureus by contacting with SEQ ID genome-selected lytic bacteriophage(s)

A method for decontaminating a material, comprising contacting the material with an antibacterial composition in an amount effective to decontaminate the material, wherein the antibacterial composition comprises at least one bacteriophage having lytic activity against at least one Staphylococcus aureus strain, the at least one bacteriophage being selected from bacteriophages having a genome comprising a nucleotide sequence of any one of SEQ ID NOs: 1 to 4 or a sequence having at least 95% identity thereto, and wherein the material is contaminated with the S. aureus strain.

Determining a cocktail of bacteriophages effective against a target S. aureus strain using SEQ ID genome selections with optional synergy/antagonism and genus constraint

A method for determining a cocktail of bacteriophages effective against a target Staphylococcus aureus strain, comprising separately contacting the target Staphylococcus aureus strain, or a sample containing said strain, with bacteriophages having genomes comprising the nucleotide sequences of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, and/or SEQ ID NO: 4 or sequences having at least 95% identity thereto, selecting bacteriophages which exhibit lytic activity on the strain, optionally further selecting active bacteriophages which, when combined together, exhibit synergistic activity on the strain and/or no antagonism, and/or optionally selecting active bacteriophages which belong to different genus, and combining said selected bacteriophages.

Across the independent claims, the main coverage repeatedly defines lytic bacteriophage activity against S. aureus and constrains the phage selection by genome nucleotide sequence of SEQ ID NOs: 1 to 4 or sequences with at least 95% identity. The independent claims further cover an antibacterial composition with a preservative-containing pharmaceutically acceptable excipient or carrier, treating S. aureus infections, modifying microbial flora to improve a condition where S. aureus is present, decontaminating an S. aureus-contaminated material, and determining an effective bacteriophage cocktail via strain contact, lytic activity selection, and optional selection based on synergy, no antagonism, and different genus.

Stated Advantages

Documented Applications

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