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Publication Number
US-12134640-B2
Publication Date
2024-11-05
Expiration Date
Abstract
The present invention provides polypeptides comprising or consisting of an amino acid sequence derived from collagen type VI or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant of derivative thereof, wherein the polypeptide, fragment, variant, fusion or derivative is capable of killing or attenuating the growth of microorganisms. Related aspects of the invention provide corresponding isolated nucleic acid molecules, vectors and host cells for making the same. Additionally provided are pharmaceutical compositions comprising a polypeptide of the invention, as well as methods of use of the same in the treatment and/or prevention of microbial infections and in wound care. Also provided are a method of killing microorganisms in vitro and a medical device associated with the pharmaceutical composition.
Core Innovation
The invention relates to collagen type VI-derived antimicrobial polypeptides, including polypeptides, fragments, variants, and derivatives of a sequence selected from the group consisting of an SEQ ID NO: 2 sequence derived from the α1(VI) chain of collagen type VI, a fragment of SEQ ID NO: 2 comprising at least 20 contiguous amino acids, and a variant of SEQ ID NO: 2 with at least 80% sequence identity. The polypeptide length is between 20 and 200 amino acids.
The collagen type VI-derived polypeptide, fragment, or variant is capable of killing or attenuating the growth of microorganisms. The document further describes an antimicrobial mechanism associated with membrane binding and disruption, including membrane disruption effects such as blebbing and cytoplasmic exudation, as well as membrane permeabilization and leakage observations.
The document also states functional outcomes including an antimicrobial spectrum against microorganisms such as Gram-positive and Gram-negative microorganisms, and multidrug-resistant strains, and includes comparative antimicrobial activity relative to LL-37. In addition, the document describes an anti-endotoxic effect against LPS, including suppression of nitrite (Griess reagent), and wound-healing activity, including promoted wound closure and epithelial regeneration.
Claims Coverage
The independent claim is directed to collagen type VI (α1(VI) chain)-derived antimicrobial polypeptides having defined sequence selection criteria and a specified length range, with the functional requirement of killing or attenuating microorganism growth.
Collagen type VI-derived antimicrobial polypeptide sequence selection
A polypeptide comprising an amino acid sequence selected from the group consisting of: SEQ ID NO: 2 derived from the α1(VI) chain of collagen type VI; a fragment of SEQ ID NO: 2 comprising at least 20 contiguous amino acids of SEQ ID NO: 2; and a variant of SEQ ID NO: 2 with at least 80% sequence identity to SEQ ID NO: 2, wherein the polypeptide, fragment, or variant is capable of killing or attenuating the growth of microorganisms.
Defined polypeptide length range
The polypeptide is between 20 and 200 amino acids in length.
Overall claim coverage centers on collagen type VI (α1(VI) chain)-derived antimicrobial polypeptides defined by SEQ ID NO: 2 selection, constrained by a 20–200 amino acid length requirement, and defined by capability to kill or attenuate microorganism growth.
Stated Advantages
Kills or attenuates the growth of microorganisms.
Provides antimicrobial activity with an antimicrobial spectrum that includes Gram-positive and Gram-negative microorganisms and multidrug-resistant strains.
Exhibits antimicrobial activity relative to LL-37.
Provides an anti-endotoxic effect, including suppression of nitrite induced by LPS.
Promotes wound closure and wound healing, including epithelial regeneration.
Documented Applications
Medical uses in infection prevention and wound care, including medical devices coated, impregnated, or covalently linked with the polypeptides, and kits including such devices/materials.
Pharmaceutical compositions formulated for administration using pharmaceutically acceptable excipients, including optional oral, parenteral, and topical routes.
Sterilising solutions described as containing or involving the polypeptides for killing/attenuating microbial growth.
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