Antimicrobial peptides
Inventors
BACHNOFF, Niv • COHEN-KUTNER, Moshe
Assignees
Publication Number
US-10538559-B2
Publication Date
2020-01-21
Expiration Date
2036-02-17
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Abstract
The invention provides a peptide comprising: a core amino acid sequence, which is identical or similar to the amino acid sequence of a member of the Cecropin family. The invention further provides a nucleic acid sequence encoding the peptide and a vector comprising said nucleic acid. The invention further provides a pharmaceutical composition comprising said peptide or said nucleic acid. The invention further provides methods of treating an infection, overcoming inherent or acquired resistance of a microorganism to an antibiotic agent or disinfecting a wound, the methods comprises administering the peptide to a subject in need thereof.
Core Innovation
The invention provides degradation-resistant peptides based on the Cecropin family of antimicrobial peptides, naturally found in insects, which are potent antibacterial agents. These peptides comprise a core amino acid sequence identical or similar to members of the Cecropin family, extended at their N- and/or C-termini by groups capable of forming covalent bonds, thereby creating cyclic peptides or homomultimer assemblies with enhanced stability. The invention also provides nucleic acid sequences encoding these peptides, vectors containing such nucleic acids, pharmaceutical compositions comprising the peptides or nucleic acids, and methods of treatment involving administration of these peptides.
The problem addressed is the widespread emergence of resistant strains of microorganisms due to extensive use of current antibiotics. Many native antimicrobial peptides, such as natural Cecropins, are sensitive to proteolytic degradation, limiting their therapeutic efficacy and stability. The invention solves this by genetically engineering Cecropin-based peptides to include cysteine residues at their termini, allowing for covalent cyclization which imparts higher stability while maintaining or enhancing antimicrobial activity. This overcomes the rapid degradation issue and yields peptides effective against resistant bacteria.
Claims Coverage
The patent includes one independent claim focused on a specific cyclic peptide and its related pharmaceutical compositions and uses. The main inventive features concern the sequence identity, cyclic nature, pharmaceutical formulations, methods of treating infections, overcoming bacterial resistance, and disinfecting wounds.
Cyclic peptide with high sequence identity to SEQ ID NO: 7
A cyclic peptide that has an amino acid sequence having at least 95% sequence identity to the amino acid sequence set forth in SEQ ID NO: 7, including embodiments with at least 99% identity or the exact sequence.
Pharmaceutical compositions comprising the cyclic peptide
Pharmaceutical compositions that contain the cyclic peptide described, formulated in various dosage forms such as liquids, creams, gels, pastes, emulsions, ointments, lotions, transdermal systems, injections, suspensions, patches, sprays, capsules, or tablets.
Method of treating bacterial infections caused by gram negative bacteria
Administering the cyclic peptide to a subject in need thereof for treating bacterial infections specifically caused by gram negative bacteria.
Overcoming inherent or acquired resistance of gram negative bacteria
A method involving contacting gram negative bacteria, including members of Enterobacteriaceae spp., Pseudomonas spp., Salmonella spp., or Acinetobacter spp., with the cyclic peptide to overcome inherent or acquired antibiotic resistance.
Disinfecting cutaneous abscesses caused by gram negative bacteria
A method for disinfecting a cutaneous abscess by contacting it with the cyclic peptide where the infection is caused by gram negative bacteria.
The claims cover a stable cyclic peptide highly similar or identical to a specified sequence, its pharmaceutical compositions in multiple forms, and methods of treatment addressing bacterial infections including resistant gram negative strains and wound disinfection.
Stated Advantages
The peptides exhibit enhanced stability against proteolytic degradation compared to native Cecropins while maintaining or improving their antimicrobial activity.
The cyclic peptides demonstrate potent bactericidal effects against a broad range of both gram-negative and gram-positive bacteria, including multi-drug resistant strains.
The peptides specifically target bacteria without causing hemolysis or cytotoxicity to mammalian cells, indicating high safety and selectivity.
The invention provides peptides effective in overcoming inherent or acquired resistance of microorganisms to current antibiotics.
The peptides retain antimicrobial activity in physiological conditions, including presence of serum and in vivo infection models.
Documented Applications
Therapeutic use in treating infections caused by bacterial, viral, and fungal pathogens, administering the peptide to subjects in need.
Overcoming inherent or acquired antibiotic resistance of microorganisms by contacting them with the peptides or pharmaceutical compositions.
Disinfecting wounds including blister wounds, soft tissue wounds, cutaneous abscesses, surgical wounds, lacerations, burn wounds, ulcers, oral infections, periodontal diseases, and partial or full thickness burns.
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