Antibacterial composition and a method of treating staphylococcal infections with the antibacterial composition
Inventors
Yoon, Seong Jun • JUN, Soo Youn • Jung, Gi Mo • Kang, Sang Hyeon
Assignees
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Publication Number
US-11229677-B2
Publication Date
2022-01-25
Expiration Date
Abstract
A method of treating staphylococcal infections includes administering to a subject an effective amount of an antibacterial composition having a broad bactericidal activity. The antibacterial composition includes a first antibacterial protein consisting of the amino acid sequence as set forth in SEQ. ID. NO: 1 and/or a second antibacterial protein consisting of the amino acid sequence as set forth in SEQ. ID. NO: 2.
Core Innovation
The invention describes an antibacterial composition and a method of treating staphylococcal infections by administering an effective amount of the antibacterial composition to a subject. The antibacterial composition has broad bactericidal activity against a panel of Staphylococcus species including Staphylococcus arlettae, Staphylococcus aureus, Staphylococcus epidermidis, Staphylococcus hemolyticus, Staphylococcus lugdunensis, Staphylococcus saprophyticus, Staphylococcus warneri, and Staphylococcus xylosus, as well as additional Staphylococcus species listed in the document.
The composition is based on two endolysin-derived antibacterial proteins. The antibacterial composition includes a mixture of a first isolated recombinant antibacterial protein having the amino acid sequence of SEQ ID NO: 1 and a second isolated recombinant antibacterial protein having the amino acid sequence of SEQ ID NO: 2, and the mixture is defined by specific mole-percent ranges including 15–35 mole % of SEQ ID NO: 1 and 55–85 mole % of SEQ ID NO: 2, with an example mole-percent ratio of 25/75.
The invention further includes at least one selected from L-histidine, D-sorbitol, CaCl2, and poloxamer 188. A post-translationally modified form of one of the proteins is described, specifically an initiator methionine-deleted form, and the document indicates that this form is obtained without requiring a cleavage step.
The provided experimental support indicates rapid bactericidal activity in a panel of Staphylococcus strains, with measured outcomes expressed in TOD50 values, and specificity described as activity against tested Staphylococcus strains with no activity against tested non-Staphylococcus strains. In vivo mouse models are described for single and mixed staphylococcal bloodstream infections, reporting increased survival and bacterial clearance.
Claims Coverage
One independent claim is provided (clm-00001). It covers a treating method defined by broad bactericidal activity across a specified Staphylococcus species panel, a two-protein mixture based on SEQ ID NO: 1 and SEQ ID NO: 2 with defined mole-percent ranges, and inclusion of at least one formulation additive selected from L-histidine, D-sorbitol, CaCl2, and poloxamer 188.
Treating staphylococcal infections with a broad bactericidal composition
A method of treating staphylococcal infections comprising administering an effective amount of an antibacterial composition that has broad bactericidal activity against all Staphylococcus species listed in the claim.
Two-protein antibacterial mixture defined by SEQ ID NO: 1 and SEQ ID NO: 2
The antibacterial composition includes a mixture of 15–35 mole % of a first isolated antibacterial protein consisting of the amino acid sequence of SEQ ID NO: 1 and 55–85% of a second isolated recombinant antibacterial protein consisting of the amino acid sequence of SEQ ID NO: 2.
Formulation additives selected from L-histidine, D-sorbitol, CaCl2, and poloxamer 188
The antibacterial composition further includes at least one selected from L-histidine, D-sorbitol, CaCl2, and poloxamer 188.
The claim coverage centers on treating staphylococcal infections with a defined two-protein endolysin-derived antibacterial composition (SEQ ID NO: 1 and SEQ ID NO: 2) formulated with at least one selected additive, while requiring broad bactericidal activity across a specified list of Staphylococcus species.
Stated Advantages
Broad bactericidal activity against the listed Staphylococcus species.
Rapid bactericidal activity within the reported TOD50 timeframe in multiple Staphylococcus strains.
Activity against tested Staphylococcus strains with no activity against tested non-Staphylococcus strains.
In vivo efficacy in mouse models for single and mixed staphylococcal bloodstream infections, including increased survival and clearance of bacterial counts.
Documented Applications
Treatment of staphylococcal bloodstream infections in mouse models, including single and mixed staphylococcal bloodstream infections.
Treatment of specific staphylococcal infection categories listed in the dependent claims, including skin infections, soft-tissue infections, toxic shock syndrome, purpura fulminans, endocarditis, osteomyelitis, pneumonia, infections related to prosthetic devices, and urinary tract infections.
Treatment of skin infections selected from folliculitis, furuncles, impetigo, wound infections, and scalded skin syndrome.
Treatment of staphylococcal infections related to prosthetic devices including prosthetic joints and heart valves, vascular shunts, grafts, or catheters.
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