Peptides and compositions for prevention of cell adhesion and methods of using same
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Publication Number
US-11174299-B2
Publication Date
2021-11-16
Expiration Date
Abstract
Compositions comprising an isolated peptide, which may for example optionally comprise a sequence consisting of SVHSFDYDWYNV, or any cyclized version thereof, 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
A peptide selected from a defined group of amino-acid sequences, including SEQ ID NO: 6, 13-25, 3, 26, and 1, is used for anti-adhesion and anti-biofilm performance. The peptides include variants of CSFSQNKSVHSFDYDWYNVSDQADLKNQLGDAGYV (SEQ ID NO: 6) and CSFSQNKSVHSFDYDWYNVSDQADLKNC (SEQ ID NO: 1), and the peptide may be cyclized in embodiments.
The document describes prevention of initial microbial substrate adhesion by contacting cells or coating surfaces or devices with the peptide. This is directed to inhibiting microbial adhesion and biofilm formation without bactericidal or bacteriostatic lethality, with emphasis on non-cytotoxic and cytostatic performance.
The peptide is further described in connection with surface and device coatings, including covalent surface immobilization. The document describes an EDC reaction and medical-device contexts, including contact lenses, with activity against Pseudomonas aeruginosa and Staphylococcus aureus.
Claims Coverage
The independent claim defines peptides by membership in a specified set of sequences, while dependent claims add cyclization, peptide concentration, and provision on surfaces or devices by covalent attachment using EDC. The claim set centers on a specific peptide sequence family comprising SEQ ID NOs: 6, 13-25, 3, 26, and 1.
Defined peptide sequence set
A peptide selected from the group consisting of SFSQNKSVHSFDYDWYNVSDQADLKNQLGDAGYV (SEQ ID NO: 6), SVHSFDYDWYNVS (SEQ ID NO: 13), SVHSFDYDWYNVSD (SEQ ID NO: 14), KSVHSFDYDWYNVSD (SEQ ID NO: 15), SVHSFDYDWYNVSDQ (SEQ ID NO: 16), NKSVHSFDYDWYNVSDQ (SEQ ID NO: 17), NKSVHSFDYDWYNVSDQA (SEQ ID NO: 18), QNKSVHSFDYDWYNVSDQA (SEQ ID NO: 19), QNKSVHSFDYDWYNVSDQAD (SEQ ID NO: 20), SQNKSVHSFDYDWYNVSDQAD (SEQ ID NO: 21), SQNKSVHSFDYDWYNVSDQADL (SEQ ID NO: 22), FSQNKSVHSFDYDWYNVSDQADL (SEQ ID NO: 23), FSQNKSVHSFDYDWYNVSDQADLK (SEQ ID NO: 24), SFSQNKSVHSFDYDWYNVSDQADL (SEQ ID NO: 25), SFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO: 3), CSFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO: 26), and CSFSQNKSVHSFDYDWYNVSDQADLKNC (SEQ ID NO: 1).
Cyclized peptide option
The peptide is cyclized.
Covalent peptide coating on a surface
Coating of the peptide on the surface is provided by covalent attachment of the peptide to the surface.
EDC-mediated covalent attachment
Covalent attachment of the peptide to the surface is provided by 1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) reaction.
Peptide concentration range in the composition
The peptide is present in the composition at a concentration from about 0.1 μM to about 10 μM.
Medical device selection including contact lens
The medical device is selected from artificial blood vessels, catheters and other devices for the removal or delivery of fluids to patients, artificial hearts, artificial kidneys, orthopedic pins, prosthetic joints, plates, urinary devices, ventricular or arterio-venous shunts, prostheses, breast implants, penile prostheses, vascular grafting prostheses, aneurysm repair devices, mechanical heart valves, artificial joints, artificial larynxes, otological implants, anastomotic devices, vascular catheter ports, vascular stents, clamps, embolic devices, wound drain tubes, ocular lenses, dental implants, hydrocephalus shunts, pacemakers and implantable defibrillators, needleless connectors, voice prostheses, urological tubes, biliary tubes, endotracheal tubes, peripherally-insertable central venous catheters, dialysis catheters, long term tunneled central venous catheters, peripheral venous catheters, short term central venous catheters, arterial catheters, pulmonary catheters, Swan-Ganz catheters, urinary catheters, peritoneal catheters, and a contact lens.
Overall, the claims cover specific peptides defined by sequence identity, with dependent claims narrowing embodiments to cyclized peptides, compositions containing the peptides within a defined concentration range, and peptide provision on surfaces by covalent attachment using an EDC reaction, including application to broad medical-device categories such as a contact lens.
Stated Advantages
Prevention of initial microbial substrate adhesion and inhibition of biofilm formation without bactericidal or bacteriostatic lethality.
Non-cytotoxic and cytostatic performance, supported by in vitro cytotoxicity results consistent with non-cytotoxic performance (ISO 10993-5).
Documented Applications
Coating or contacting cells with the peptide to prevent initial microbial substrate adhesion and reduce biofilm formation.
Use on medical devices and surfaces, including contact lenses (Etafilcon A), with dose-dependent inhibition of Pseudomonas aeruginosa adhesion in PBS and tear-like fluid.
In vitro activity against strong biofilm producer strains of Pseudomonas aeruginosa and against Staphylococcus aureus.
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