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Publication Number
US-11136374-B2
Publication Date
2021-10-05
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 or 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 polypeptides, including polypeptides comprising an amino acid sequence selected from SEQ ID NO: 5 derived from the α1(VI) chain of collagen type VI, fragments of SEQ ID NO: 5 comprising at least 20 contiguous amino acids, and variants of SEQ ID NO: 5 having at least 80% sequence identity. The polypeptides, fragments, or variants are between 20 and 200 amino acids in length and are capable of killing or attenuating the growth of microorganisms.
The disclosed functional properties include antimicrobial activity associated with killing or attenuating growth of microorganisms, with the polypeptide described as binding to microorganism membranes and disrupting those membranes. The document also describes promoting wound closure and exhibiting antimicrobial activity greater than or equal to LL-37. In addition, the polypeptide is described as exerting an anti-endotoxic effect, including suppression of LPS-induced nitrite.
The invention further covers related compositions and uses, including nucleic acids, vectors, host cells, and pharmaceutical compositions comprising the collagen type VI-derived polypeptides. It also describes medical device/wound-care uses involving device coating and/or impregnation with the collagen type VI-derived polypeptide to prevent infection. Coverage is described as including Gram-positive and Gram-negative microorganisms and multidrug-resistant strains such as MRSA/MRPA.
Claims Coverage
The document provides one independent claim covering a defined collagen type VI-derived polypeptide sequence space and its microorganism-killing or microorganism-growth-attenuating capability. Dependent claims refine sequence constraints and extend coverage to functional/mechanistic attributes, formulation, and device or wound-care contexts.
Collagen type VI-derived polypeptides killing or attenuating microorganisms
A polypeptide comprising an amino acid sequence selected from SEQ ID NO: 5 derived from the α1(VI) chain of collagen type VI, a fragment of SEQ ID NO: 5 comprising at least 20 contiguous amino acids, or a variant of SEQ ID NO: 5 with at least 80% sequence identity, wherein the polypeptide, fragment, or variant is between 20 and 200 amino acids in length and is capable of killing or attenuating the growth of microorganisms.
Sequence identity-fragment length constraints
A polypeptide (per the collagen type VI-derived definition) limited to a fragment containing at least a specified contiguous segment length and/or a variant having a specified minimum sequence identity threshold to SEQ ID NO: 5.
Membrane binding, membrane disruption, wound closure, LL-37 benchmark, and anti-endotoxic effect
A polypeptide (per the collagen type VI-derived definition) described as binding to microorganism membranes, disrupting those membranes, promoting wound closure, exhibiting antimicrobial activity greater than or equal to LL-37, and exerting an anti-endotoxic effect.
Pharmaceutical composition with pharmaceutically acceptable components
A pharmaceutical composition comprising a polypeptide (per the collagen type VI-derived definition) and pharmaceutically acceptable formulation components.
Optional chemical modifications of the polypeptide
A polypeptide (or fragment/variant) whose amino acids are modified or derivatized by one or more specified chemical modifications, including PEGylation, amidation, esterification, acylation, acetylation, and/or alkylation.
Overall, the claim coverage centers on collagen type VI-derived polypeptides defined by SEQ ID NO: 5, fragment/variant constraints, and a microorganism killing or growth-attenuating function, with dependent claims further specifying identity/length refinements, membrane-binding/disruption and wound-related and anti-endotoxic functional attributes, and coverage through pharmaceutical formulations and optional polypeptide chemical modifications.
Stated Advantages
Can kill or attenuate the growth of microorganisms.
Antimicrobial activity is described as greater than or equal to LL-37.
Described as promoting wound closure.
Exerts an anti-endotoxic effect, including suppression of LPS-induced nitrite.
Reduced cytotoxicity to mammalian cells within bactericidal concentrations.
Broad microorganism coverage including Gram-positive and Gram-negative microorganisms and multidrug-resistant strains such as MRSA/MRPA.
Documented Applications
Medical device/wound-care infection prevention via coating and/or impregnation with the collagen type VI-derived polypeptide.
Pharmaceutical compositions for antimicrobial use against microorganisms.
Use contexts described as including wound closure/healing.
In vivo application described via mouse survival improvement (SFV33/GVR28 vs PBS).
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