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-11654166-B2
Publication Date
2023-05-23
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 provides bacteriophage compositions comprising two or more obligately lytic bacteriophages, at least one of which has a nucleotide sequence with at least 90% identity to SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3. These compositions are substantially free of bacterial components, such as endotoxins and bacterial host proteins, and may include a cryoprotectant or other excipient. The bacteriophages are capable of infecting and lysing Staphylococcus aureus, including methicillin-resistant strains, and the compositions can include naturally occurring or non-naturally occurring bacteriophages, mutants, or identity variants.
The compositions may comprise a storage medium suitable for storage at or below 8°C, are formulated for compatibility with multiple modes of administration (including intravenous, topical, aerosol, and intra-articular), and contain specific ratios and concentrations of bacteriophages to achieve broad activity against Staphylococcus aureus. Each individual bacteriophage is not prone to generalized transduction and does not carry antibiotic resistance genes, thereby enhancing the safety and efficacy of the composition.
The problem addressed by this invention is the increasing resistance of human pathogens to antibiotics, including Staphylococcus aureus strains that are resistant to multiple drugs. Current treatments can fail due to antibiotic resistance, and there is a need for alternative therapies that can effectively treat infections, including biofilm-associated infections, and do not disrupt native flora. The disclosed bacteriophage compositions offer a targeted, potentially synergistic approach to treating Staphylococcus aureus infections, including those unresponsive to standard antibiotic therapy.
Claims Coverage
The patent claims primarily cover three inventive features relating to bacteriophage compositions for targeting Staphylococcus infections.
Bacteriophage compositions comprising two or more obligately lytic bacteriophages with defined sequence identity
The invention specifies compositions substantially free of bacterial components and comprising at least two obligately lytic bacteriophages. At least one bacteriophage in the composition must have a nucleotide sequence with at least 90% identity to any one of SEQ ID NO: 1, SEQ ID NO: 2, or SEQ ID NO: 3. These bacteriophages are selected to infect and lyse methicillin-resistant or methicillin-sensitive Staphylococcus aureus, and the composition may further include pharmaceutically acceptable carriers, excipients, or cryoprotectants. The compositions may be in various formulations including liquid, lyophilized, or frozen forms and are designed for therapeutic use against Staphylococcus infections.
Bacteriophage composition including non-naturally occurring and transduction-resistant phages
The claims cover compositions containing one or more obligately lytic bacteriophages where at least one is not naturally-occurring, and each individual bacteriophage is not prone to generalized transduction and does not carry antibiotic resistance genes. The inventive feature requires sequence identity to SEQ ID NO: 1, 2, or 3, and emphasizes biosafety attributes such as the absence of genes for antibiotic resistance and the reduced potential for genetic material transfer.
Bacteriophage compositions used in defined storage and dosage parameters
The claimed compositions are formulated for storage at or below 8°C and comprise a storage medium (typically with cryoprotectant, such as glycerol or sucrose). The inventive features specify the dosages (from 1×10^5 to 3×10^11 PFU per milliliter), and the compositions can be administered in various formulations. This feature ensures stability during storage and administration, maintaining efficacy and sterility for clinical application.
The claims collectively establish inventive features of bacteriophage compositions defined by obligately lytic phages with sequence identity to reference phages, biosafety features preventing resistance transmission, and practical storage and formulation parameters to ensure clinical usability.
Stated Advantages
The bacteriophage compositions are effective against a broad spectrum of Staphylococcus species and strains, including multi-drug resistant Staphylococcus aureus.
The compositions are substantially free of bacterial components such as endotoxins and host cell proteins, enhancing safety for clinical use.
As obligately lytic phages, the bacteriophages are not prone to generalized transduction and do not carry antibiotic resistance genes, reducing potential safety concerns.
The compositions are efficacious in treating infections that do not respond to one or more antibiotics, offering an alternative to conventional antibacterial agents.
A combination of bacteriophage composition and antibiotic therapy can provide a synergistic therapeutic effect.
The compositions are compatible with multiple modes of administration (intravenous, topical, aerosol, and more), increasing their clinical versatility.
Documented Applications
Treatment of Staphylococcus aureus bacterial infections, including those caused by both methicillin-resistant and methicillin-sensitive strains.
Use in treating non-pulmonary Staphylococcus aureus infections such as rhinosinusitis, urinary tract infection, intra-abdominal infection, skin infections, bacteremia, endocarditis, implant infections (including cardiac implant, prosthetic joint, and prosthetic valve infections).
Use as an adjunct or alternative to antibiotic therapy for infections that do not respond to antibiotics or standard-of-care antibiotics.
Treatment of infections characterized by bacterial biofilm formation.
Formulation as a disinfectant or topical composition for application to skin, medical equipment, wound dressings, or surfaces.
Application in non-medical areas such as food hygiene, agriculture, crop protection, and environmental hygiene.
Modification of the microbial flora in humans by targeted lysis of Staphylococcus aureus.
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