Peptides and compositions for prevention of cell adhesion and methods of using same

Inventors

Zlotkin, Amir • Kestenboim, Hen

Assignees

Dispersebio Ltd

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Publication Number

US-9029318-B2

Patent

Publication Date

2015-05-12

Expiration Date


Abstract

Compositions comprising an isolated peptide, which may for example optionally comprise a sequence selected from the group consisting of YDYNWY (SEQ ID NO: 1), YDYNLY (SEQ ID NO: 2), YDYSFY (SEQ ID NO: 63), FDYNFY (SEQ ID NO: 3), FDYNLY (SEQ ID NO: 4), FDYNWY (SEQ ID NO: 5), YDWNLY (SEQ ID NO: 6), YDWHLY (SEQ ID NO: 7) and WDYNLY (SEQ ID NO: 8), extracted from organisms such as aquatic organisms and moss or any other sequence described herein, and methods of using same, including for treatment of or prevention of formation of microbial biofilms and against adhesion of a cell to a surface.

Core Innovation

The patent describes isolated natural/cyclic peptide sequences derived from aquatic organisms and moss, including YDYNWY (SEQ ID NO: 1), YDYNLY (SEQ ID NO: 2), FDYNFY (SEQ ID NO: 3), FDYNLY (SEQ ID NO: 4), FDYNWY (SEQ ID NO: 5), YDWNLY (SEQ ID NO: 6), YDWHLY (SEQ ID NO: 7), and WDYNLY (SEQ ID NO: 8). These peptides prevent or reduce microbial biofilm formation and cell adhesion, while being devoid of cytotoxic activity and devoid of cytostatic activity, i.e., without bactericidal or bacteriostatic effects.

The disclosed peptides are cyclic peptides with a length up to about 30–50 amino acids. The patent further connects the peptides to a conserved region of an anemone cytotoxin, while specifically claiming the conserved region lacks cytotoxicity, supporting use as anti-adhesion agents targeting adhesion and biofilm stages rather than microbial growth inhibition.

The document discloses broader implementation via pharmaceutical compositions and compositions suitable for coatings of medical devices, as well as marine anti-fouling and reverse osmosis treatment and anti-fouling contexts. It also provides experimental support references, including MS/MS identification of an active fraction and alignment-based identification of conserved domains, and includes evaluation approaches for biofilm inhibition and for RO membrane biofouling and anti-fouling assays.

Claims Coverage

The partial claim set includes three independent claims. Across the independent claims, the coverage is centered on compositions devoid of cytotoxic or cytostatic activity that include cyclic isolated peptides of specified sequences, up to 50 amino acids, to prevent or reduce adhesion and to prevent or reduce biofilm formation or biofilm fouling.

Preventing adhesion of a single cell organism with a non-cytotoxic/cytostatic cyclic peptide

A method of preventing adhesion of a single cell organism to a surface by contacting the organism with a composition devoid of cytotoxic or cytostatic activity, the composition comprising a cyclic isolated peptide consisting of a length up to 50 amino acids and comprising one of the sequences selected from YDYNWY (SEQ ID NO: 1), YDYNLY (SEQ ID NO: 2), FDYNFY (SEQ ID NO: 3), FDYNLY (SEQ ID NO: 4), WDYNLY (SEQ ID NO: 8), FDYNWY (SEQ ID NO: 5), YDWNLY (SEQ ID NO: 6), and YDWHLY (SEQ ID NO: 7), wherein the composition prevents or reduces adhesion.

Treating water to prevent or reduce biofilm formation or fouling of a filter

A method of treating water to prevent or reduce biofilm formation or fouling of a filter by treating the water with a composition devoid of cytotoxic or cytostatic activity and comprising an isolated peptide, wherein the peptide comprises one of the sequences selected from YDYNWY (SEQ ID NO: 1), YDYNLY (SEQ ID NO: 2), FDYNFY (SEQ ID NO: 3), FDYNLY (SEQ ID NO: 4), WDYNLY (SEQ ID NO: 8), FDYNWY (SEQ ID NO: 5), YDWNLY (SEQ ID NO: 6), and YDWHLY (SEQ ID NO: 7), wherein the peptide is cyclic and consists of a length up to 50 amino acids.

Preventing or reducing biofilm formation in an external fluid not originating from an animal body

A method of preventing or reducing biofilm formation in an external fluid which does not originate from an animal body by treating the fluid with a composition devoid of cytotoxic or cytostatic activity and comprising an isolated cyclic peptide consisting of a length up to 50 amino acids, the peptide comprising one of the sequences selected from YDYNWY (SEQ ID NO: 1), YDYNLY (SEQ ID NO: 2), FDYNFY (SEQ ID NO: 3), FDYNLY (SEQ ID NO: 4), WDYNLY (SEQ ID NO: 8), FDYNWY (SEQ ID NO: 5), YDWNLY (SEQ ID NO: 6), and YDWHLY (SEQ ID NO: 7).

Across the independent claims, the claim coverage is directed to compositions devoid of cytotoxic or cytostatic activity that include specified cyclic isolated peptides, up to 50 amino acids, to prevent or reduce adhesion and to prevent or reduce biofilm formation or biofilm fouling in defined contexts.

Stated Advantages

Prevents or reduces adhesion of a single cell organism to a surface.

Prevents or reduces biofilm formation.

Prevents or reduces fouling of a filter.

The composition and peptide are devoid of cytotoxic activity and cytostatic activity, i.e., not bactericidal or bacteriostatic.

Documented Applications

Marine anti-fouling and reverse osmosis (RO) treatment for preventing or reducing microbial biofilm formation and biofouling of RO membranes/filters.

Surface coating of medical devices to prevent or reduce microbial adhesion and biofilm formation.

Pharmaceutical compositions for use as anti-adhesion/biofilm-inhibiting compositions.

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