Antimicrobial peptides and compositions, methods, articles and kits relating thereto
Inventors
Bishop, Barney • van Hoek, Monique • BARKSDALE, Stephanie
Assignees
Publication Number
US-11180528-B2
Publication Date
2021-11-23
Expiration Date
2039-11-26
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Abstract
Peptides are described herein, in particular peptides having antimicrobial properties, as are compositions, articles, and kits comprising such peptides, and methods for using the peptides.
Core Innovation
The invention provides peptides, specifically those with antimicrobial properties, which are characterized by defined amino acid sequences and their variants as described in Formula (I) and exemplified in SEQ ID NO:2, 4, 5, 6, 7, or 8. These peptides may include conservative or non-conservative substitutions, insertions, additions, or deletions but exclude the native Apo6 APOC167-88 sequence. The peptides and their compositions, articles, and kits are designed for diverse uses, including therapeutic and prophylactic treatment.
The problem addressed by this invention stems from the increasing ineffectiveness of existing antimicrobial agents against pathogens, particularly those classified as biodefense risks or exhibiting single- or multi-drug resistance. Francisella tularensis, a Gram-negative bacterium and causative agent of tularemia, is a noted example with both naturally high virulence and evolving antibiotic resistance, for which current treatments can be insufficient.
The peptides disclosed demonstrate potent activity against a wide range of microbial organisms, including Gram-negative and Gram-positive bacteria and other microbes. These peptides are incorporated into compositions, devices, and kits, and the invention further includes methods for using them in treating and preventing infections, promoting wound healing, preventing or treating endotoxemia, determining and diagnosing lipopolysaccharide (LPS), and reducing or eliminating LPS from compositions.
Claims Coverage
The patent contains several independent claims, each directed to a distinct inventive feature relating to antimicrobial peptides and their use.
Peptide with defined antimicrobial sequence
A peptide comprising the amino acid sequence set forth in SEQ ID NO:2, 4, 5, 6, 7, or 8. - The peptide may include substitutions, insertions, additions, or deletions, except that it does not comprise the native Apo6 APOC167-88 sequence. - These sequences are designed for antimicrobial activity.
Composition comprising antimicrobial peptide
A composition comprising the peptide as defined above. - The composition may further comprise an excipient. - Intended for antimicrobial use or other stated applications.
Article of manufacture containing antimicrobial peptide
An article of manufacture comprising the defined antimicrobial peptide. - The article may be a hygiene product, wound dressing, or an invasive device with the peptide attached to its surface.
Kit comprising antimicrobial peptide
A kit comprising the peptide as defined, possibly with instructions for use. - Enables convenient therapeutic, diagnostic, or preventative applications.
Method for treating microbial infection in a subject
A method for treating infection by a microbial organism in a subject by administering to the subject the defined peptide. - The method covers different dosages and may include use against drug-resistant organisms.
Method for preventing or inhibiting growth of microorganisms or biofilm on a surface
A method comprising contacting a surface with a composition containing the peptide to prevent, reduce, or inhibit growth of a microbial organism or biofilm.
Method for promoting wound healing in a subject
A method comprising administering the peptide to a subject to promote wound healing.
Method for treating or preventing endotoxemia in a subject
A method comprising administering an amount of the peptide effective to treat or prevent endotoxemia.
Method for determining lipopolysaccharide in a sample
A method comprising contacting a sample with the peptide so that LPS binds to the peptide to form a complex, and detecting the complex.
Method for diagnosing an LPS-associated disorder
A method comprising forming a complex between LPS and the peptide so that the LPS binds, and detecting the complex in a subject.
Method for treating a composition comprising LPS
A method comprising contacting a composition with the peptide so that LPS binds to the peptide to form a complex, and separating the complex from the composition to reduce or eliminate LPS.
The claims collectively provide broad coverage of peptides with defined antimicrobial sequences, their compositions and articles, and various therapeutic, prophylactic, diagnostic, and preparative methods utilizing these peptides.
Stated Advantages
The peptides provide new and effective antimicrobial agents against pathogens, including drug-resistant and biodefense-relevant organisms.
They can reduce or inhibit the growth of microbial organisms and biofilms on surfaces, including medical devices and wounds.
Certain peptides can treat or prevent endotoxemia by binding endotoxins such as LPS.
They allow for rapid detection and diagnosis of LPS or LPS-associated disorders via specific binding interactions.
Peptides or compositions can promote wound healing in both infected and uninfected wounds.
Compositions and methods provide alternatives when resistance to conventional antibiotics is determined or suspected.
Documented Applications
Treatment of infection by microbial organisms in humans and animals, including those resistant to antibiotics.
Prevention, reduction, or inhibition of growth of microorganisms or biofilms on surfaces such as medical devices, prosthetics, implants, catheters, staples, sutures, and tubing.
Promotion of wound healing in subjects (humans, companion animals, livestock), including infected and uninfected wounds.
Treatment or prevention of endotoxemia in subjects by binding and neutralizing endotoxins.
Detection of lipopolysaccharide (LPS) in biological samples by binding and forming detectable complexes.
Diagnosis of LPS-associated disorders in subjects via formation and detection of LPS-peptide complexes.
Treatment of compositions containing LPS (e.g., parenteral solutions, cell culture reagents, blood products) by removing or eliminating the LPS through peptide binding.
Inclusion in kits and articles of manufacture (such as wound dressings or hygiene products) for antimicrobial and wound-healing uses.
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