US6617142B2
Expired / Lapsed
US
⏱️ 0.0 years remaining
Method for attachment of biomolecules to medical device surfaces
Assignee: Medtronic Inc
•
Filing: 1999-02-24
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Granted: 2003-09-09
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Expires: 2019-02-24
Abstract
Abstract Methods are provided for forming a coating of an immobilized biomolecule on a surface of a medical device to impart improved biocompatibility for contacting tissue and bodily fluids. A biomolecule such as a glycoprotein having an unsubstituted amide moiety is combined with an amine forming agent to form an amine-functional biomolecule. The amine-functional biomolecule is combined with a medical device surface having a chemical moiety such as aldehyde, epoxide, isocyanate, 1,2-dicarbonyl, phosphate, sulphate or carboxylate to form a chemical bond immobilizing the biomolecule on the surface. The chemical bond may be combined with a reducing agent or a stabilizing agent. The aldehyde moiety may be formed by combining a periodate with a 2-aminoalcohol moiety or a 1,2-dihydroxy moiety. Alternatively, an amine-functional medical device surface is combined with a biomolecule having a chemical moiety that reacts with an amine moiety. In another embodiment, the amine-functional biomolecule is converted to a guanidino-functional biomolecule and is combined with a medical device surface having a chemical moiety that reacts with a guanidino moiety. Alternatively, an amine-functional medical device surface is converted to a guanidino-functional surface and is combined with a biomolecule having the chemical moiety. Biomolecules may be crosslinked by combining the amine-functional or guanidino-functional biomolecule with a biomolecule having a chemical moiety that forms a chemical bond with an amine moiety or a guanidino moiety.
Inventors
- 👤 James R. Keogh
- 👤 Paul V. Trescony
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-22 22:55
CPC Classifications
A; A61; A61L; A61L33/00; A61L33/18; A61L27/00; A61L27/14; A61L27/22; A61L27/24; A61L27/28; A61L27/34; A61L29/00; A61L29/08; A61L29/085; A61L31/00; A61L31/08; A61L31/10; A61L33/0005; A61L33/0011; A61L33/0029; A61L33/0047; A61L33/0076; A61L33/0082; A61L33/06; A61L33/12; A61L33/128; C; C08; C08L; C08L89/00; Y; Y10; Y10S; Y10S530/00; Y10S530/81; Y10S530/811; Y10S530/812; Y10S530/815; Y10S530/816
Claims Analysis
Total Claims: 59
Claim 1
Independent Claim
171 words
A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the steps of: (a) providing the medical device, the device having a biomaterial disposed on or forming a surface thereof, the biomaterial comprising an unsubstituted amide moiety; (b) combining the amide moiety with an amine forming agent to form an amine-functional surface; (c) combining the amine-functional surface with a guanidino forming agent to form a guanidino-functional surface; (d) providing a biomolecule, the biomolecule comprising a chemical moiety selected from the group consisting of an aldehyde moiety formed by combining a periodate with a 2-aminoalcohol moiety, an aldehyde moiety formed by combining a periodate with a 1,2-dihydroxy moiety, an epoxide moiety, an isocyanate moiety, a 1,2-dicarbonyl moiety, a phosphate moiety, a sulphate moiety and a carboxylate moiety; and (e) combining the chemical moiety with the guanidino-functional surface to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.
Claim 2
Independent Claim
171 words
A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the steps of: (a) providing the medical device, the device having a biomaterial disposed on or forming a surface thereof, the biomaterial comprising an unsubstituted amide moiety; (b) combining the amide moiety with an amine forming agent to form an amine-functional surface; (c) combining the amine-functional surface with a guanidino forming agent to form a guanidino-functional surface; (d) providing a biomolecule, the biomolecule comprising a chemical moiety selected from the group consisting of an aldehyde moiety formed by combining a periodate with a 2-aminoalcohol moiety, an aldehyde moiety formed by combining a periodate with a 1,2-dihydroxy moiety, an epoxide moiety, an isocyanate moiety, a 1,2-dicarbonyl moiety, a phosphate moiety, a sulphate moiety and a carboxylate moiety; and (e) combining the chemical moiety with the guanidino-functional surface to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.
Claim 3
Dependent Claim
18 words
The method of claim 1 comprising the further step of combining a stabilizing agent with the chemical bond.
Claim 4
Dependent Claim
13 words
The method of claim 2 wherein the stabilizing agent is a borate ion.
Claim 5
Dependent Claim
39 words
The method of claim 1 wherein the guanidino forming agent is selected from the group consisting of S-ethylthiouronium bromide, S-ethylthiouronium chloride, O-methylisourea, O-methylisouronium sulfate, O-methylisourea hydrogen sulfate, S-methylisothiourea, 2-methyl-1-nitroisourea, aminoiminomethanesulfonic acid, cyanamide, cyanoguanide, dicyandiamide, 3,5-dimethyl-1-guanylpyrazole nitrate and 3,5-dimethyl pyrazole.
Claim 6
Independent Claim
132 words
A method of forming a coating on a surface of a medical device, the method comprising the steps of: (a) providing the medical device, the device having a biomaterial disposed on or forming a surface thereof, the biomaterial comprising an unsubstituted amide moiety; (b) combining the amide moiety with an amine forming agent to form an amine-functional surface; (c) combining the amine-functional surface with a guanidino forming agent to form a guanidino-functional surface; (d) providing a biomolecule, the biomolecule comprising a chemical moiety selected from the group consisting of a 1,2-dicarbonyl moiety, a phosphate moiety, a sulphate moiety, and a carboxylate moiety; and (e) combining the chemical moiety with the guanidino-functional surface to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.
Claim 7
Independent Claim
132 words
A method of forming a coating on a surface of a medical device, the method comprising the steps of: (a) providing the medical device, the device having a biomaterial disposed on or forming a surface thereof, the biomaterial comprising an unsubstituted amide moiety; (b) combining the amide moiety with an amine forming agent to form an amine-functional surface; (c) combining the amine-functional surface with a guanidino forming agent to form a guanidino-functional surface; (d) providing a biomolecule, the biomolecule comprising a chemical moiety selected from the group consisting of a 1,2-dicarbonyl moiety, a phosphate moiety, a sulphate moiety, and a carboxylate moiety; and (e) combining the chemical moiety with the guanidino-functional surface to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.
Claim 8
Dependent Claim
72 words
The method of claim 5 , wherein the device is selected from the group consisting of a blood-contacting medical device, a tissue-contacting medical device, a bodily fluid-contacting medical device, an implantable medical device, an extracorporeal medical device, a blood oxygenator, a blood pump, tubing for carrying blood, an endoprosthesis medical device, a vascular graft, a stent, a pacemaker lead, a heart valve, temporary intravascular medical device, a catheter and a guide wire.
Claim 9
Dependent Claim
14 words
The method of claim 5 , wherein the biomaterial comprises an amino acid residue.
Claim 10
Dependent Claim
34 words
The method of claim 5 , wherein the amine forming agent is selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene.
Claim 11
Dependent Claim
90 words
The method of claim 5 , wherein the biomolecule is selected from the group consisting of an antithrombotic agent, an anti-inflammatory, an antibody, an antigen, an immunoglobulin, an enzyme, a hormone, a neurotransmitter, a cytokine, a protein, a globular protein, a cell attachment protein, a peptide, a cell attachment peptide, a proteoglycan, a toxin, an antibiotic agent, an antibacterial agent, an antimicrobial agent, a polysaccharide, a carbohydrate, a fatty acid, a drug, a vitamin, a DNA segment, a RNA segment, a nucleic acid, a lectin, a dye and a ligand.
Claim 12
Dependent Claim
14 words
The method of claim 5 , wherein the biomolecule is a naturally occurring biomolecule.
Claim 13
Dependent Claim
14 words
The method of claim 5 , wherein the biomolecule is a chemically synthesized biomolecule.
Claim 14
Dependent Claim
21 words
The method of claim 5 , wherein the biomolecule is selected from the group consisting of a glycopeptide and a glycoprotein.
Claim 15
Dependent Claim
32 words
The method of claim 5 , wherein at least a portion of the surface forms at least one of a tube, a rod, a membrane, a balloon, a bag and a sheet.
Claim 16
Dependent Claim
142 words
The method of claim 5 , wherein the device comprises at least one of a biocompatible material selected from the group consisting of a metal, a titanium, a titanium alloy, a tin-nickel alloy, a shape memory alloy, an aluminum oxide, a platinum, a platinum alloy, a stainless steel, a MP35N stainless steel, a elgiloy, a stellite, a pyrolytic carbon, a silver carbon, a glassy carbon, a polymer, a polyamide, a polycarbonate, a polyether, a polyester, a polyolefin, a polyethylene, a polypropylene, a polystyrene, a polyurethane, a polyvinylchloride, a polyvinylpyrrolidone, a silicone elastomer, a fluoropolymer, a polyacrylate, a polyisoprene, a polytetrafluoroethylene, a rubber, a ceramic, a hydroxapatite, a human protein, a human tissue, an animal protein, an animal tissue, a bone, a skin, a tooth, a collagen, a laminin, a elastin, a fibrin, a wood, a cellulose, a compressed carbon and a glass.
Claim 17
Independent Claim
116 words
A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the steps of: (a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising an unsubstituted amide moiety; (b) combining the amide moiety with an amine forming agent to form an amine-functional surface; (c) providing a biomolecule, the biomolecule comprising a chemical moiety selected from the group consisting of an epoxide moiety and an isocyanate moiety; and (d) combining the chemical moiety with the surface to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.
Claim 18
Independent Claim
116 words
A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the steps of: (a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising an unsubstituted amide moiety; (b) combining the amide moiety with an amine forming agent to form an amine-functional surface; (c) providing a biomolecule, the biomolecule comprising a chemical moiety selected from the group consisting of an epoxide moiety and an isocyanate moiety; and (d) combining the chemical moiety with the surface to form a chemical bond, the chemical bond immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.
Claim 19
Dependent Claim
72 words
The method of claim 15 , wherein the device is selected from the group consisting of a blood-contacting medical device, a tissue-contacting medical device, a bodily fluid-contacting medical device, an implantable medical device, an extracorporeal medical device, a blood oxygenator, a blood pump, tubing for carrying blood, an endoprosthesis medical device, a vascular graft, a stent, a pacemaker lead, a heart valve, temporary intravascular medical device, a catheter and a guide wire.
Claim 20
Dependent Claim
14 words
The method of claim 15 , wherein the biomaterial comprises an amino acid residue.
Claim 21
Dependent Claim
34 words
The method of claim 15 , wherein the amine forming agent is selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene.
Claim 22
Dependent Claim
90 words
The method of claim 15 , wherein the biomolecule is selected from the group consisting of an antithrombotic agent, an anti-inflammatory, an antibody, an antigen, an immunoglobulin, an enzyme, a hormone, a neurotransmitter, a cytokine, a protein, a globular protein, a cell attachment protein, a peptide, a cell attachment peptide, a proteoglycan, a toxin, an antibiotic agent, an antibacterial agent, an antimicrobial agent, a polysaccharide, a carbohydrate, a fatty acid, a drug, a vitamin, a DNA segment, a RNA segment, a nucleic acid, a lectin, a dye and a ligand.
Claim 23
Dependent Claim
14 words
The method of claim 15 , wherein the biomolecule is a naturally occurring biomolecule.
Claim 24
Dependent Claim
14 words
The method of claim 15 , wherein the biomolecule is a chemically synthesized biomolecule.
Claim 25
Dependent Claim
21 words
The method of claim 15 , wherein the biomolecule is selected from the group consisting of a glycopeptide and a glycoprotein.
Claim 26
Dependent Claim
32 words
The method of claim 15 , wherein at least a portion of the surface forms at least one of a tube, a rod, a membrane, a balloon, a bag and a sheet.
Claim 27
Dependent Claim
142 words
The method of claim 15 , wherein the device comprises at least one of a biocompatible material selected from the group consisting of a metal, a titanium, a titanium alloy, a tin-nickel alloy, a shape memory alloy, an aluminum oxide, a platinum, a platinum alloy, a stainless steel, a MP35N stainless steel, a elgiloy, a stellite, a pyrolytic carbon, a silver carbon, a glassy carbon, a polymer, a polyamide, a polycarbonate, a polyether, a polyester, a polyolefin, a polyethylene, a polypropylene, a polystyrene, a polyurethane, a polyvinylchloride, a polyvinylpyrrolidone, a silicone elastomer, a fluoropolymer, a polyacrylate, a polyisoprene, a polytetrafluoroethylene, a rubber, a ceramic, a hydroxapatite, a human protein, a human tissue, an animal protein, an animal tissue, a bone, a skin, a tooth, a collagen, a laminin, a elastin, a fibrin, a wood, a cellulose, a compressed carbon and a glass.
Claim 28
Independent Claim
156 words
A method of forming a crosslinked coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the steps of: (a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising unsubstituted amide moieties: (b) combining the amide moieties with an amine forming agent to form amine moieties; (c) providing biomolecules having at least one chemically reactive moiety selected from the group consisting of a 1,2-dihydroxy moiety and a 2-aminoalcohol moiety, combining periodate with the biomolecules to oxidize the chemically reactive moiety to form aldehyde moieties; (d) combining the biomolecules with the surface; (e) allowing the aldehyde moieties to combine with the amine moieties to form imine moieties; and (f) reacting the imine moieties with a reducing agent to form amine linkages, the amine linkages immobilizing and crosslinking the biomolecules on the surface, the immobilized and crosslinked biomolecules forming the coating.
Claim 29
Independent Claim
156 words
A method of forming a crosslinked coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the steps of: (a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising unsubstituted amide moieties: (b) combining the amide moieties with an amine forming agent to form amine moieties; (c) providing biomolecules having at least one chemically reactive moiety selected from the group consisting of a 1,2-dihydroxy moiety and a 2-aminoalcohol moiety, combining periodate with the biomolecules to oxidize the chemically reactive moiety to form aldehyde moieties; (d) combining the biomolecules with the surface; (e) allowing the aldehyde moieties to combine with the amine moieties to form imine moieties; and (f) reacting the imine moieties with a reducing agent to form amine linkages, the amine linkages immobilizing and crosslinking the biomolecules on the surface, the immobilized and crosslinked biomolecules forming the coating.
Claim 30
Dependent Claim
24 words
The method of claim 25 , wherein the periodate comprises at least one of periodic acid, sodium periodate, alkali metal periodates, and potassium periodate.
Claim 31
Dependent Claim
28 words
The method of claim 25 , wherein the periodate is combined with the 2-aminoalcohol moieties in an aqueous solution having a pH between about 4 and about 9.
Claim 32
Dependent Claim
30 words
The method of claim 25 , wherein the periodate is combined with the 2-aminoalcohol moieties in an aqueous solution having a temperature between about 0 and about 50 degrees Celsius.
Claim 33
Dependent Claim
17 words
The method of claim 25 , wherein the oxidizing step is performed in the absence of light.
Claim 34
Dependent Claim
27 words
The method of claim 25 , wherein the biomolecules and the surface are combined in an aqueous solution having a pH between about 6 and about 10.
Claim 35
Dependent Claim
29 words
The method of claim 25 , wherein the biomolecules and the surface are combined in an aqueous solution having a temperature between about 0 and about 50 degrees Celsius.
Claim 36
Dependent Claim
22 words
The method of claim 25 , wherein the reducing agent comprises at least one of sodium borohydride, sodium cyanoborohydride, and amine borane.
Claim 37
Dependent Claim
29 words
The method of claim 25 , wherein the reducing agent is combined with the imine moieties in an aqueous solution having a pH between about 6 and about 10.
Claim 38
Dependent Claim
31 words
The method of claim 25 , wherein the reducing agent is combined with the imine moieties in an aqueous solution having a temperature between about 0 and about 50 degrees Celsius.
Claim 39
Independent Claim
269 words
A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the ordered steps of: (a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising an unsubstituted amide moiety; (b) combining the amide moiety with an amine forming agent selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene to form an amine-functional surface; (c) providing a biomolecule, the biomolecule comprising a 2-aminoalcohol moiety, combining a periodate comprising at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate, with the biomolecule in the absence of light and in an aqueous solution having a pH between about 4 and about 9 and a temperature between about 0 and about 50 degrees Celsius, the periodate oxidizing the 2-aminoalcohol moiety to form an aldehyde moiety; (d) combining the aldehyde moiety with the surface in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an imine moiety; and (e) reacting the imine moiety with at least one reducing agent selected from the group consisting of sodium borohydride, sodium cyanoborohydride and amine borane in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an amine linkage, the amine linkage immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.
Claim 40
Independent Claim
269 words
A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the ordered steps of: (a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising an unsubstituted amide moiety; (b) combining the amide moiety with an amine forming agent selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene to form an amine-functional surface; (c) providing a biomolecule, the biomolecule comprising a 2-aminoalcohol moiety, combining a periodate comprising at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate, with the biomolecule in the absence of light and in an aqueous solution having a pH between about 4 and about 9 and a temperature between about 0 and about 50 degrees Celsius, the periodate oxidizing the 2-aminoalcohol moiety to form an aldehyde moiety; (d) combining the aldehyde moiety with the surface in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an imine moiety; and (e) reacting the imine moiety with at least one reducing agent selected from the group consisting of sodium borohydride, sodium cyanoborohydride and amine borane in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an amine linkage, the amine linkage immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.
Claim 41
Dependent Claim
72 words
The method of claim 35 , wherein the device is selected from the group consisting of a blood-contacting medical device, a tissue-contacting medical device, a bodily fluid-contacting medical device, an implantable medical device, an extracorporeal medical device, a blood oxygenator, a blood pump, tubing for carrying blood, an endoprosthesis medical device, a vascular graft, a stent, a pacemaker lead, a heart valve, temporary intravascular medical device, a catheter and a guide wire.
Claim 42
Dependent Claim
14 words
The method of claim 35 , wherein the biomaterial comprises an amino acid residue.
Claim 43
Dependent Claim
90 words
The method of claim 35 , wherein the biomolecule is selected from the group consisting of an antithrombotic agent, an anti-inflammatory, an antibody, an antigen, an immunoglobulin, an enzyme, a hormone, a neurotransmitter, a cytokine, a protein, a globular protein, a cell attachment protein, a peptide, a cell attachment peptide, a proteoglycan, a toxin, an antibiotic agent, an antibacterial agent, an antimicrobial agent, a polysaccharide, a carbohydrate, a fatty acid, a drug, a vitamin, a DNA segment, a RNA segment, a nucleic acid, a lectin, a dye and a ligand.
Claim 44
Independent Claim
14 words
The method of claims 35 , wherein the biomolecule is a naturally occurring biomolecule.
Claim 45
Dependent Claim
14 words
The method of claim 35 , wherein the biomolecule is a chemically synthesized biomolecule.
Claim 46
Dependent Claim
13 words
The method of claim 35 , wherein-the biomolecule comprises an amino acid residue.
Claim 47
Dependent Claim
27 words
The method of claim 41 , wherein the amino acid residue is selected from the group consisting of a N-terminal serine, a N-terminal threonine and a 5-hydroxylysine.
Claim 48
Dependent Claim
32 words
The method of claim 35 , wherein at least a portion of the surface forms at least one of a tube, a rod, a membrane, a balloon, a bag and a sheet.
Claim 49
Dependent Claim
141 words
The method of claim 35 , wherein the device comprises at least one of a biocompatible material selected from the group consisting of a metal, a titanium, a titanium alloy, a tin-nickel alloy, a shape memory alloy, an aluminum oxide, a platinum, a platinum alloy, a stainless steel, a MP35N stainless steel, a elgiloy, a stellite, a pyrolytic carbon, a silver carbon, a glassy carbon, a polymer, a polyamide, a polycarbonate, a polyether, a polyester, a polyolefin, a polyethylene, a polypropylene, a polystyrene, a polyurethane, a polyvinylchloride, a polyvinylpyrrolidone, a silicone elastomer, a fluoropolymer, a polyacrylate, a polyisoprene, a polytetrafluoroethylene, a rubber, a-ceramic, a hydroxapatite, a human protein, a human tissue, an animal protein, an animal tissue, a bone, a skin, a tooth, a collagen, a laminin, a elastin, a fibrin, a wood, a cellulose, a compressed carbon and a glass.
Claim 50
Independent Claim
269 words
A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the ordered steps of: (a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising an unsubstituted amide moiety; (b) combining the amide moiety with an amine forming agent selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene to form an amine-functional surface; (c) providing a biomolecule, the biomolecule comprising a 1,2-dihydroxy moiety, combining a periodate comprising at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate, with the biomolecule in the absence of light and in an aqueous solution having a pH between about 4 and about 9 and a temperature between about 0 and about 50 degrees Celsius, the periodate oxidizing the 1,2-dihydroxy moiety to form an aldehyde moiety; (d) combining the aldehyde moiety with the surface in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an imine moiety; and (e) reacting the imine moiety with at least one reducing agent selected from the group consisting of sodium borohydride, sodium cyanoborohydride and amine borane in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an amine linkage, the amine linkage immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.
Claim 51
Independent Claim
269 words
A method of forming a coating on a surface of a medical device, the coating imparting improved biocompatibility characteristics to the surface, the method comprising the ordered steps of: (a) providing the medical device, the device having a suitable biomaterial forming the surface, the biomaterial comprising an unsubstituted amide moiety; (b) combining the amide moiety with an amine forming agent selected from the group consisting of bromine, bromide, bromite, hypobromite, chlorine, chloride, chlorite, hypochlorite, lead tetraacetate, benzyltrimethylammonium tribromide, [bis(trifluoroacetoxy)iodo]benzene, hydroxy(tosyloxy)iodobenzene and iodosylbenzene to form an amine-functional surface; (c) providing a biomolecule, the biomolecule comprising a 1,2-dihydroxy moiety, combining a periodate comprising at least one of a periodic acid, a sodium periodate, an alkali metal periodate, and a potassium periodate, with the biomolecule in the absence of light and in an aqueous solution having a pH between about 4 and about 9 and a temperature between about 0 and about 50 degrees Celsius, the periodate oxidizing the 1,2-dihydroxy moiety to form an aldehyde moiety; (d) combining the aldehyde moiety with the surface in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an imine moiety; and (e) reacting the imine moiety with at least one reducing agent selected from the group consisting of sodium borohydride, sodium cyanoborohydride and amine borane in an aqueous solution having a pH between about 6 and about 10 and a temperature between about 0 and about 50 degrees Celsius to form an amine linkage, the amine linkage immobilizing the biomolecule on the surface, the immobilized biomolecule forming the coating.
Claim 52
Dependent Claim
72 words
The method of claim 45 , wherein the device is selected from the group consisting of a blood-contacting medical device, a tissue-contacting medical device, a bodily fluid-contacting medical device, an implantable medical device, an extracorporeal medical device, a blood oxygenator, a blood pump, tubing for carrying blood, an endoprosthesis medical device, a vascular graft, a stent, a pacemaker lead, a heart valve, temporary intravascular medical device, a catheter and a guide wire.
Claim 53
Dependent Claim
14 words
The method of claim 45 , wherein the biomaterial comprises an amino acid residue.
Claim 54
Dependent Claim
90 words
The method of claim 45 , wherein the biomolecule is selected from the group consisting of an antithrombotic agent, an anti-inflammatory, an antibody, an antigen, an immunoglobulin, an enzyme, a hormone, a neurotransmitter, a cytokine, a protein, a globular protein, a cell attachment protein, a peptide, a cell attachment peptide, a proteoglycan, a toxin, an antibiotic agent, an antibacterial agent, an antimicrobial agent, a polysaccharide, a carbohydrate, a fatty acid, a drug, a vitamin, a DNA segment, a RNA segment, a nucleic acid, a lectin, a dye and a ligand.
Claim 55
Dependent Claim
14 words
The method of claim 45 , wherein the biomolecule is a naturally occurring biomolecule.
Claim 56
Dependent Claim
14 words
The method of claim 45 , wherein the biomolecule is a chemically synthesized biomolecule.
Claim 57
Dependent Claim
21 words
The method of claim 45 , wherein the biomolecule is selected from the group consisting of a glycopeptide and a glycoprotein.
Claim 58
Dependent Claim
32 words
The method of claim 45 , wherein at least a portion of the surface forms at least one of a tube, a rod, a membrane, a balloon, a bag and a sheet.
Claim 59
Dependent Claim
142 words
The method of claim 45 , wherein the device comprises at least one of a biocompatible material selected from the group consisting of a metal, a titanium, a titanium alloy, a tin-nickel alloy, a shape memory alloy, an aluminum oxide, a platinum, a platinum alloy, a stainless steel, a MP35N stainless steel, a elgiloy, a stellite, a pyrolytic carbon, a silver carbon, a glassy carbon, a polymer, a polyamide, a polycarbonate, a polyether, a polyester, a polyolefin, a polyethylene, a polypropylene, a polystyrene, a polyurethane, a polyvinylchloride, a polyvinylpyrrolidone, a silicone elastomer, a fluoropolymer, a polyacrylate, a polyisoprene, a polytetrafluoroethylene, a rubber, a ceramic, a hydroxapatite, a human protein, a human tissue, an animal protein, an animal tissue, a bone, a skin, a tooth, a collagen, a laminin, a elastin, a fibrin, a wood, a cellulose, a compressed carbon and a glass.
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| 3.5 Years (Year 4) | 2006-09-08 | 2007-03-10 | 2007-09-09 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2010-09-08 | 2011-03-10 | 2011-09-09 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2014-09-08 | 2015-03-10 | 2015-09-09 | $7700.00 | Window Closed / Lapsed |