Peptides and compositions for prevention of cell adhesion and methods of using same
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Publication Number
US-11566054-B2
Publication Date
2023-01-31
Expiration Date
Abstract
Compositions comprising an isolated peptide, which may for example optionally comprise a sequence selected from the group consisting of FDYDWY (SEQ ID NO: 2), SFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO: 3) or CSFSQNKSVHSFDYDWYNVSDQADLKNC (SEQ ID NO: 1), 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
The invention concerns isolated peptide compositions comprising specific amino acid sequences selected from FDYDWY (SEQ ID NO: 2) and variant peptide sequences, including SFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO: 3) and CSFSQNKSVHSFDYDWYNVSDQADLKNC (SEQ ID NO: 1). The peptides are provided in cyclized and non-cyclized forms and are presented for preventing microbial and cell adhesion at initial stages, including prevention of biofilm formation by inhibiting substrate adhesion.
The background and biological discussion link the conserved peptide sequences to GPCR 137B (GPR137B) extracellular regions and to sea-anemone/ciona-related sequences. The disclosed peptides are characterized as having anti-adhesive activity while not being bactericidal, and they are described as remaining active under lyophilization, with emphasis on resistance to lyophilization.
The document further describes uses for coated surfaces and broader surface/device applications, including medical devices and coatings intended to provide anti-fouling effects, with additional mention of household, and water systems. Example results are reported showing inhibition of Pseudomonas aeruginosa attachment at biofilm initial stages without growth inhibition, and the emphasis is on anti-adhesion rather than killing.
Claims Coverage
The provided independent claims are directed to (i) a water/biological-fluid-immersed coated surface with a cyclized antibacterial peptide of selected sequences, (ii) a medical device with a polymeric matrix incorporating a peptide of the selected sequences, and (iii) a medical device at least partially coated with at least one of the selected peptide sequences. Across the independents, the coverage centers on cyclized peptides from a defined FDYDWY sequence set, with a peptide length limit and device-surface implementations.
Cyclized antibacterial peptide-coated surface immersed in water or body fluid
A surface is immersed in water or a body fluid and is coated with a composition comprising a cyclized antibacterial peptide comprising an amino acid sequence selected from the group consisting of FDYDWY (SEQ ID NO: 2), SFDYDWY (SEQ ID NO: 7), SFDYDWYN (SEQ ID NO: 8), HSFDYDWYN (SEQ ID NO: 9), HSFDYDWYNV (SEQ ID NO: 10), VHSFDYDWYNV (SEQ ID NO: 11), VHSFDYDWYNVS (SEQ ID NO: 12), SVHSFDYDWYNVS (SEQ ID NO: 13), SVHSFDYDWYNVSD (SEQ ID NO: 14), KSVHSFDYDWYNVSD (SEQ ID NO: 15), KSVHSFDYDWYNVSDQ (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), SFSQNKSVHSFDYDWYNVSDQADLK (SEQ ID NO: 25), SFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO: 3), CSFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO: 26), CSFSQNKSVHSFDYDWYNVSDQADLKNC (SEQ ID NO: 1), SVHSFDYDWYNV (SEQ ID NO: 28), and combinations thereof.
Cyclized antibacterial peptide-coated surface with peptide length limit
A surface is coated with a composition comprising a cyclized antibacterial peptide comprising an amino acid sequence selected from the group consisting of FDYDWY (SEQ ID NO: 2), SFDYDWY (SEQ ID NO: 7), SFDYDWYN (SEQ ID NO: 8), HSFDYDWYN (SEQ ID NO: 9), HSFDYDWYNV (SEQ ID NO: 10), VHSFDYDWYNV (SEQ ID NO: 11), VHSFDYDWYNVS (SEQ ID NO: 12), SVHSFDYDWYNVS (SEQ ID NO: 13), SVHSFDYDWYNVSD (SEQ ID NO: 14), KSVHSFDYDWYNVSD (SEQ ID NO: 15), KSVHSFDYDWYNVSDQ (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), SFSQNKSVHSFDYDWYNVSDQADLK (SEQ ID NO: 25), SFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO: 3), CSFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO: 26), CSFSQNKSVHSFDYDWYNVSDQADLKNC (SEQ ID NO: 1), SVHSFDYDWYNV (SEQ ID NO: 28), and combinations thereof, wherein the peptide is up to 35 amino acids in length.
Medical device with polymeric matrix incorporating peptide composition
A medical device comprising a polymeric matrix into which a composition comprising a peptide comprising the amino acid sequence selected from the group consisting of FDYDWY (SEQ ID NO: 2), SFDYDWY (SEQ ID NO: 7), SFDYDWYN (SEQ ID NO: 8), HSFDYDWYN (SEQ ID NO: 9), HSFDYDWYNV (SEQ ID NO: 10), VHSFDYDWYNV (SEQ ID NO: 11), VHSFDYDWYNVS (SEQ ID NO: 12), SVHSFDYDWYNVS (SEQ ID NO: 13), SVHSFDYDWYNVSD (SEQ ID NO: 14), KSVHSFDYDWYNVSD (SEQ ID NO: 15), KSVHSFDYDWYNVSDQ (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), SFSQNKSVHSFDYDWYNVSDQADLK (SEQ ID NO: 25), SFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO: 3), CSFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO: 26), and CSFSQNKSVHSFDYDWYNVSDQADLKNC (SEQ ID NO: 1), SVHSFDYDWYNV (SEQ ID NO: 28) and combinations thereof is incorporated, wherein the medical device is selected from the group consisting of artificial blood vessels, catheters and other devices for the removal or delivery of fluids to patients, artificial hearts, artificial kidneys, orthopedic pins, prosthetic joints, 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, and voice prostheses.
Medical device at least partially coated with peptide composition
A medical device at least partially coated with a peptide comprising at least one sequence selected from the group consisting of FDYDWY (SEQ ID NO: 2), SFDYDWY (SEQ ID NO: 7), SFDYDWYN (SEQ ID NO: 8), HSFDYDWYN (SEQ ID NO: 9), HSFDYDWYNV (SEQ ID NO: 10), VHSFDYDWYNV (SEQ ID NO: 11), VHSFDYDWYNVS (SEQ ID NO: 12), SVHSFDYDWYNVS (SEQ ID NO: 13), SVHSFDYDWYNVSD (SEQ ID NO: 14), KSVHSFDYDWYNVSDQ (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), SFSQNKSVHSFDYDWYNVSDQADLK (SEQ ID NO: 25), SFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO: 3), CSFSQNKSVHSFDYDWYNVSDQADLKN (SEQ ID NO: 26), and CSFSQNKSVHSFDYDWYNVSDQADLKNC (SEQ ID NO: 1), SVHSFDYDWYNV (SEQ ID NO: 28) and combinations thereof, wherein the medical device is selected from the group consisting of artificial blood vessels, catheters and other devices for the removal or delivery of fluids to patients, artificial hearts, artificial kidneys, orthopedic pins, prosthetic joints, 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, and voice prostheses.
Across the independent claims, the coverage is consistently centered on surfaces and medical devices associated with anti-adhesive/biofilm initial stage prevention, using a cyclized antibacterial peptide selected from a defined FDYDWY sequence set, with scope further constrained by a peptide length limit and medical-device or device-surface implementations as specified in the claims.
Stated Advantages
Prevents microbial and cell adhesion at initial stages by inhibiting substrate adhesion, including preventing biofilm formation.
Anti-adhesive activity is described without bactericidal activity and without growth inhibition.
Resistance to lyophilization is emphasized.
Documented Applications
Preventing biofilm formation by inhibiting substrate adhesion on surfaces immersed in water or a body fluid.
Use as anti-fouling/coating for broader surface/device applications, including medical devices and coatings for anti-fouling effects.
Mentioned use contexts include medical devices, household applications, and water systems.
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