Phage therapy of E coli infections

Inventors

Pouillot, Flavie • BLOIS, Hélène

Assignees

Phaxiam Therapeutics SA

Abstract

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

Core Innovation

The disclosed subject matter concerns novel Escherichia coli (E. coli)-specific lytic bacteriophages, identified as BP539, BP700, BP753, BP814, BP953, BP954, BP970, BP1002, BP1151, BP1155, BP1168, BP1176, BP1197, BP1226, and BP1229 (SEQ ID NOs: 1–15), and their use in antibacterial compositions. The bacteriophages are described as exhibiting high selectivity, in that lysis is not observed for various non-E. coli species, and as having a potent productive lytic effect (PLE), with PLE values reported as <15, often <10.

The document further describes compositions that include at least two distinct lytic bacteriophages selected for genomic membership in SEQ ID NOs: 1 to 15, or sequences having at least 99% identity thereto. The compositions are characterized by lytic profiles against E. coli strains, including strains from the ECOR collection and pathogenic and antibiotic-resistant E. coli strains, and are described in the context of defined lysis coverage thresholds, including coverage reported as more than 90% of all bacterial strains of the EcoR collection.

In addition, the document reports use of the disclosed phage compositions in in vitro and in vivo contexts, including killing of MDR/hemorrhagic/clinical hospital isolates and performance in a mouse burn infection model with reported survival rates. The document also describes composition aspects such as pharmaceutically and veterinary acceptable excipients, formulation types including liquid, solid, and lyophilized forms, bacteriophage concentration ranges, and diagnostic and predictive testing based on in vitro lytic activity against subject-derived E. coli isolates.

Claims Coverage

The independent claims identify four categories of claimed subject matter: treating an infection in a mammal, improving a mammal’s condition by modifying the microbial flora, decontaminating a material, and an antibacterial composition with a pharmaceutically acceptable excipient/carrier and preservative. Across these independent claims, the inventive features center on selecting at least two distinct lytic bacteriophages active against E. coli strains, with the phage genome defined by SEQ ID NOs: 1 to 15 or at least 99% identity thereto.

Across the independent claims, the claimed core coverage is the use of an antibacterial composition containing at least two distinct lytic bacteriophages active against an E. coli strain, where selection is defined by genome nucleotide sequence matching SEQ ID NOs: 1–15 or sequences having at least 99% identity thereto. This phage-selection feature is implemented in methods for treating an E. coli infection in a mammal, improving a mammal’s condition by modifying microbial flora containing the E. coli strain, decontaminating a material, and in a corresponding composition claim that includes a pharmaceutically acceptable excipient/carrier with a preservative.

Stated Advantages

Documented Applications