Therapeutic bacteriophage compositions for treating Staphylococcus infection
Inventors
MORALES, Sandra P. • MEARNS, Gillian • RANKIN, Deborah A. • SMREKAR, Frenk
Assignees
Ampliphi Biosciences Corp • Armata Pharmaceuticals Inc
Publication Number
US-12239677-B2
Publication Date
2025-03-04
Expiration Date
2039-01-02
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Abstract
The present disclosure relates to a bacteriophage composition comprising one or more (suitably two or more, or three) obligately lytic bacteriophages capable of infecting and lysing Staphylococcus aureus, and use of the same for treating Staphylococcus aureus bacterial infections.
Core Innovation
The invention is a bacteriophage composition comprising one or more obligately lytic bacteriophages that target and lyse Staphylococcus aureus, including compositions with two or more or three distinct bacteriophages. These bacteriophage compositions can be substantially free of bacterial endotoxin and host cell proteins and may include a cryoprotectant or other excipient. The invention also covers the use of these compositions for treating S. aureus bacterial infections, particularly those resistant to antibiotics.
The problem addressed by the invention is the rising occurrence of human pathogens, such as S. aureus, that are resistant to antibiotics, leading to an urgent need for new treatments that circumvent traditional antibiotic resistance, are effective against biofilms, and avoid disruption of native gut flora. This issue is compounded by the limited effectiveness of current antibiotics and the clinical challenge posed by multi-drug resistant bacterial strains.
The core innovation further provides methods of treating humans with S. aureus infections by administering compositions containing bacteriophages with genomes sharing at least 93% (or specifically at least 95%) identity with SEQ ID NOs: 1, 2, or 3, with the phages selected to minimize risks of generalized transduction or transmission of antibiotic resistance genes. The invention also encompasses modifying microbial flora in humans by administering these compositions and extends to both pharmaceutical and non-medical, including hygiene and agricultural, applications.
Claims Coverage
The independent claims comprise three core inventive features relating to methods of treating S. aureus infection, compositions for confirmed non-pulmonary S. aureus infection, and modification of microbial flora using specific bacteriophage compositions.
Method of treating S. aureus infection using defined obligately lytic bacteriophage composition
A method for treating a human with a bacterial infection caused by Staphylococcus aureus comprising administration of a composition containing one or more distinct bacteriophages that infect and lyse S. aureus, each having a genome comprising a polynucleotide sequence with at least 95% identity to any one of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3.
Treatment of confirmed non-pulmonary S. aureus infections with a defined bacteriophage panel
A method for treating a human with a confirmed non-pulmonary S. aureus infection by administering a composition comprising at least two distinct bacteriophages, each able to infect and lyse S. aureus and each comprising a genome with at least 95% identity to SEQ ID NO: 1, 2, or 3, explicitly excluding pulmonary S. aureus infections.
Modification of microbial flora in humans using at least two specific S. aureus-lytic bacteriophages
A method of modifying the microbial flora in a human comprising administering a composition containing at least two distinct bacteriophages with lytic activity against S. aureus, each selected to have a genome with at least 95% identity to SEQ ID NO: 1, 2, or 3.
In summary, the claims cover methods and compositions centered around the use of obligately lytic, sequence-defined bacteriophages targeting S. aureus, including treatment of infections (particularly non-pulmonary), and manipulation of microbial flora using these phage compositions.
Stated Advantages
The bacteriophage compositions are effective against a broad spectrum of Staphylococcus species and strains, including strains resistant to chemical antibiotics and multi-drug resistant S. aureus.
The compositions can circumvent traditional mechanisms of antibiotic resistance and are potentially effective against biofilms.
The bacteriophage therapy avoids disruption of the native gut flora.
The use of obligately lytic phages minimizes the risk of generalized transduction and transfer of antibiotic resistance genes.
Compositions can be substantially free of endotoxins and bacterial host proteins, resulting in higher purity and safety.
Combinations of bacteriophages provide broader target bacteria coverage than individual phages and may show synergistic effects.
The compositions have demonstrated clinical efficacy and good tolerability in human patients, with no treatment-related serious adverse events reported.
Documented Applications
Treating Staphylococcus aureus bacterial infections in humans, including multidrug-resistant and antibiotic-resistant strains.
Treatment of non-pulmonary S. aureus infections such as rhinosinusitis, urinary tract infection, intra-abdominal infection, skin infection, skin structure infection, bacteremia, septicemia, endocarditis, cardiac implant infection, prosthetic joint infection, and prosthetic valve endocarditis.
Modification of microbial flora in a human by reducing or eliminating S. aureus using the bacteriophage composition.
Use as a medicament for the treatment of S. aureus infections, including as a co-treatment with antibiotics.
Topical, intravenous, intra-articular, and intra-sinus administration for human therapeutic purposes.
Use of the bacteriophage composition as a disinfectant for surfaces, human skin, medical equipment, bedding, furniture, walls, and floors.
Incorporation into wound dressings or bandages for inhibiting or treating bacterial contamination.
Non-medical use including food hygiene, agriculture or crop protection, and environmental hygiene applications.
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