Attached To The Carrier Via A Bridging Agent Patents (Class 530/816)
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Patent number: 5342770Abstract: The present invention provides a conjugate in essentially pure form comprising a sugar linked to a protein through a peptide linker, wherein said sugar has a reducing terminal and is free of carboxyl groups, and wherein the reducing terminal of said sugar is linked to the peptide linker. The present invention further provides a conjugate in essentially pure form comprising a sugar linked to an enzyme through a peptide linker, wherein said sugar has a reducing terminal and is free of carboxyl groups, and wherein the reducing terminal of said sugar is linked to the peptide linker. The present invention additionally provides a conjugate in essentially pure form comprising a sugar linked to lysozyme through a peptide linker, wherein said sugar has a reducing terminal and is free of carboxyl groups, and wherein the reducing terminal of said sugar is linked to the peptide linker.Type: GrantFiled: May 11, 1993Date of Patent: August 30, 1994Assignee: Chisso CorporationInventor: Nobuyuki Yamasaki
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Patent number: 5342693Abstract: The present invention is directed to multifunctional thrombo-resistant coatings for use with biomedical devices and implants, such as a coating which includes a siloxane surface onto which a plurality of amine functional groups have been bonded. Covalently bonded to the amine functional groups are a plurality of poly(ethylene oxide) chains, such that a single poly(ethylene oxide) chain is bonded to a single amine functional group. A plurality of different bioactive molecules, designed to counteract specific blood-material incompatibility reactions, are covalently bonded to poly(ethylene oxide) chains, such that a single bioactive molecule is coupled to a single polyethylene oxide chain.The methods of manufacturing the present invention include preparing a material having a siloxane surface onto which a plurality of amine functional groups have been bonded. This is achieved by plasma etching with ammonia gas or by plasma polymerization of a siloxane monomer in the presence of ammonia gas.Type: GrantFiled: March 22, 1993Date of Patent: August 30, 1994Assignee: Cardiopulmonics, Inc.Inventors: Suzanne Winters, Kenneth A. Solen, Clifton G. Sanders, J. D. Mortensen, Gaylord Berry
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Patent number: 5342772Abstract: The fluorocarbon surface of a solid or liquid support is activated with a highly fluorinated isocyanate-modified ligand or with a reactive poly(fluoroalkyl) sugar reagent containing a polyhydroxy sugar to which are attached a plurality of fluoroalkyl anchor groups, a reactive group and optionally a spacer. The activated support has application in separation of biomolecules, immobilization of biomolecules, heterogeneous diagnostic assays, and biosensors. An enzyme or other biomolecule is immobilized by contacting the activated support surface with the enzyme in the presence of a surfactant. The surfactant is preferably a neutral surfactant such as a fluoroalkyl-polyoxyethylene.Type: GrantFiled: February 10, 1993Date of Patent: August 30, 1994Assignees: E. I. du Pont de Nemours and Company, Baylor UniversityInventors: Rene Arenzen, Patrick Boivin, Robert K. Kobos, William H. Scouten, Bruce E. Smart
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Patent number: 5338770Abstract: The present invention is directed to thrombo-resistant coatings for use with gas permeable biomedical devices and implants. The coatings include a siloxane surface onto which a plurality of amine functional groups have been bonded. Covalently bonded to the amine functional groups are a plurality of poly(ethylene oxide) chains, such that a single poly(ethylene oxide) chain is bonded to a single amine functional group. A quantity of at least one bioactive molecule designed to counteract a specific blood-material incompatibility reaction is covalently bonded to the poly(ethylene oxide) chains, such that a single bioactive molecule is coupled to a single polyethylene oxide chain.The methods of manufacturing the present invention include preparing a material having a siloxane surface onto which a plurality of amine functional groups have been bonded. This is preferably achieved by plasma etching with ammonia gas.Type: GrantFiled: April 12, 1990Date of Patent: August 16, 1994Assignee: Cardiopulmonics, Inc.Inventors: Suzanne Winters, Kenneth A. Solen, Clifton G. Sanders, JD Mortensen, Gaylord Berry
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Patent number: 5336518Abstract: A treatment for metallic surfaces and devices having metallic surfaces is described. A film of heptafluorobutylmethacrylate (HFBMA) is applied to a surface by radiofrequency (RF) plasma deposition and subsequently treated with a biologically active agent. A water vapor RF plasma treatment of the HFBMA coating provides reactive groups thereon which can covalently bond to the biologically active agent. Alternatively, a spacer group can be bonded to the activated HFBMA and the biologically active agent can then be bonded to the spacer group. Devices coated according to the invention possess enhanced biocompatibility and the HFBMA coatings are durable even under severe crimping and expansion conditions.Type: GrantFiled: December 11, 1992Date of Patent: August 9, 1994Assignee: Cordis CorporationInventors: Pallassana V. Narayanan, Stephen M. Rowland, Kimberly D. Stanley
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Patent number: 5306781Abstract: Activated carboxylic acid modified polyethylene membranes useful in the C-terminal sequencing of a peptide are disclosed. The membranes comprise activated carboxylic acid modified polyethylene having a linker coupled to an amide linkage to the surface carboxyl radicals of the membrane. Activation is accomplished by reaction of the carboxylic acid modified polyethylene membrane with DCC, CDI, EDC, BOP, DICD or 2-fluoro-1-methyl pyridine.Type: GrantFiled: March 26, 1993Date of Patent: April 26, 1994Assignee: City of HopeInventor: Jerome M. Bailey
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Patent number: 5286789Abstract: Methods and compositions are provided, where oligopeptides are produced on a transparent surface while retaining transparency by the cyclical addition of protected monomers. Reagents are specifically selected to allow for efficient reproducible addition, while maintaining transparency of the support. Linkers are provided which permit retention of the oligopeptide to the surface or release of the oligopeptide at completion of the preparation of the oligopeptide. The oligopeptide bound to the support finds use in diagnostic assays, as well as other application, while the free oligopeptides may be used in a variety of ways.Type: GrantFiled: April 2, 1993Date of Patent: February 15, 1994Assignee: Applied Immune Sciences, Inc.Inventors: David Okrongly, Brian R. Clark, Jack Spesard
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Patent number: 5279954Abstract: The invention provides a means for attaching a label, support or bioactive agent to a protein with an exopeptidase at a site that is remote from the active site of the protein. More specifically the invention is directed to a method for the attachment of an amino acid, amine and alcohol nucleophile to the carboxyl terminus of a protein. In one embodiment, a labeled nucleophile is attached to a protein such as an antibody. In other embodiments, the invention is directed to a method for the attachment of a protein to an immobilization support and to a method for the attachment of a bioactive agent to a protein.Type: GrantFiled: June 30, 1989Date of Patent: January 18, 1994Assignee: Board of Regents of the University of Nebraska and BioNebraskaInventors: Fred W. Wagner, Thomas R. Coolidge, Dwane E. Wylie, Sheldon M. Schuster, William Lewis, Jay Stout
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Patent number: 5279955Abstract: Heterofunctional crosslinking agents are synthesized that covalently link molecules such as enzymes, cells, proteins and nucleic acids to a plastic substrate. The agents contain a central ring structure having a hydrophobic hydrocarbon chain that binds to a plastic substrate and distal to the hydrophobic chain one or more hydrophilic chains terminating in a reactive group that covalently binds the molecule. Immobilized molecules are useful in diagnostic assays or bioreactors. A preferred heterofunctional crosslinking agent is succinyl-olivetol-N-hydroxysuccinimide having the structure: ##STR1## This agent is prepared by reacting succinic anhydride with 5-pentyl resorcinol and condensing carboxylic acid groups with N-hydroxysuccinimide.Type: GrantFiled: March 1, 1991Date of Patent: January 18, 1994Inventors: Randall K. Pegg, Mary S. Saunders
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Patent number: 5270193Abstract: Biomolecules such as a ligand or binder for the ligand are securely but reversibly attached to a perfluorocarbon carrier with a water soluble polymer, a perfluorocarbon anchoring group and optionally a linker group. The order of steps for carrying out the attachment can vary. For example, the biomolecule is covalently attached to the polymer followed by covalently attaching the anchoring group and attaching the resultant product to the carrier. Alternatively, the anchoring group is covalently attached to the polymer followed by attaching the resultant product to the carrier and then covalently attaching a biomolecule to the polymer. The polymer may be starch, dextran, agarose, polyethylene glycol or polyvinyl alcohol. An attached ligand or binder for the ligand is useful in affinity separations and immunoassays.Type: GrantFiled: October 24, 1991Date of Patent: December 14, 1993Assignee: E. I. DuPont de Nemours and CompanyInventor: John W. D. Eveleigh
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Patent number: 5268287Abstract: A phosphazene polymer for immobilizing biologically active substances such as enzymes is prepared that does not lower activity originally possessed by the biologically active substance and does not contain a functionality which can adsorb undesired substances. The polymer has organic radicals having a functional group capable of binding a biologically active substance and organic radicals which are non-reactive and hydrophilic. The non-reactive and hydrophilic organic radicals are preferably prepared by reacting a side chain of the polymer having a primary amino group with formaldehyde or by diazotizing the primary amino group followed by hydrolysis to form a hydroxyl group. A biologically active substance immobilized on the polymer can be used to separate a substance that has affinity for the immobilized biologically active substance.Type: GrantFiled: October 26, 1990Date of Patent: December 7, 1993Assignee: Teijin LimitedInventors: Toshitsugu Matsuki, Noritsugu Saiki, Shingo Emi
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Patent number: 5268306Abstract: A specific binding pair is bound to an insoluble carrier for use in determining an analyte such as in an immunoassay. The carrier is coated with a first polymer containing a protein polymer having a molecular weight of at least about 20,000 and molecules of a first member of a specific binding pair. A second polymer containing a second member of the specific binding pair is bound to the first member on the carrier by binding of the first and second members of the specific binding pair. The first polymer is preferably more hydrophobic than the second polymer. The protein polymer can be prepared by cross-linking hydrophobic protein molecules of 10,000 to 700,000 molecular weight with a bifunctional or polyfunctional compound to obtain a protein polymer of 200,000 to 20,000,000 molecular weight. The second polymer can be the second member of the specific binding pair or the second member cross-linked with a linker or the second member cross-linked to a hydrophobic protein.Type: GrantFiled: December 23, 1991Date of Patent: December 7, 1993Assignee: Boehringer Mannheim GmbHInventors: Michael Berger, Arno Deger, Josef Maier
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Patent number: 5266471Abstract: A modified solid carrier is used to covalently immobilize biomolecules such as proteins. The carrier is based on well-known matrix materials modified to have covalently bound functional groups of formula I ##STR1## that are suitable for covalent immobilization, where A is a spacer group; X is O, S, or NH and n is 0 or 1. The modified solid carrier is prepared by reacting ammonia with glycidyl groups of a carrier to form .alpha.-hydroxy-.beta.-amino groups, reacting these groups with 2,4,6-trichloro-s-triazine to form an N-triazinyl group-containing carrier, reacting this carrier with ammonia and reacting the resultant carrier with 2,4,6-trichloro-s-triazine.Type: GrantFiled: February 25, 1991Date of Patent: November 30, 1993Assignee: ROHMInventor: Stefan Schmitt
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Patent number: 5262451Abstract: The present invention is directed to multifunctional thrombo-resistant coatings for use with biomedical devices and implants, such as a coating which includes a siloxane surface onto which a plurality of amine functional groups have been bonded. Covalently bonded to the amine functional groups are a plurality of poly(ethylene oxide) chains, such that a single poly(ethylene oxide) chain is bonded to a single amine functional group. A plurality of different bioactive molecules, designed to counteract specific blood-material incompatibility reactions, are covalently bonded to poly(ethylene oxide) chains, such that a single bioactive molecule is coupled to a single polyethylene oxide chain.The methods of manufacturing the present invention include preparing a material having a siloxane surface onto which a plurality of amine functional groups have been bonded. This is achieved by plasma etching with ammonia gas or by plasma polymerization of a siloxane monomer in the presence of ammonia gas.Type: GrantFiled: July 5, 1988Date of Patent: November 16, 1993Assignee: Cardiopulmonics, Inc.Inventors: Suzanne Winters, Kenneth A. Solen, Clifton G. Sanders, J. D. Mortensen, Gaylord Berry
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Patent number: 5258453Abstract: Compositions for the treatment of cancerous tissues in warm-blooded animals containing both an anticancer drug and a photoactivatable drug attached to copolymeric carriers are made up of a member selected from the group consisting of (a) a copolymeric carrier having attached thereto both an anticancer drug and a photoactivatable drug, (b) a mixture of copolymeric carriers wherein one copolymeric carrier has attached an anticancer drug and the other copolymeric carrier has attached a photoactivatable drug and (c) a combination of (a) and (b). The anticancer drug is attached to the polymeric carrier by side-chains which are stable in the blood stream of the warm-blooded animal but susceptible to hydrolysis by lysosomal enzymes intracellularly. The photoactivatable drug is attached by either the same degradable side-chain or by a non-degradable attachment. The polymer carrier may optionally contain a targeting moiety.Type: GrantFiled: January 21, 1992Date of Patent: November 2, 1993Assignee: University of UtahInventors: Jindrich Kopecek, Nancy L. Krinick
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Patent number: 5258492Abstract: The present invention deals with LHRH analogues which contain cytotoxic moieties and have influence on the release of gonadotropins from the pituitary gland of mammals, including humans. The compounds of this invention are represented by the formula:X--R.sup.1 --R.sup.2 --R.sup.3 -Ser-R.sup.5 --R.sup.6 (Q)-Leu-Arg-Pro-R.sup.10 --NH.sub.2whereinR.sup.1 is pGlu, Pro, D-Nal(2), or D-Phe(4Cl),R.sup.2 is His or D-Phe(4Cl),R.sup.3 is Trp, D-Trp or D-Pal(3),R.sup.5 is Tyr or Arg,R.sup.6 is D-Phe or R*.sup.6, where R*.sup.6 is D-Orn, D-Lys or D-Phe(NH.sub.2),R.sup.10 is Gly or D-Ala,X is hydrogen, a lower alkanoyl group of 2-5 carbon atoms or carbamyl,Q is bis-(2-chloroethyl)amino group provided that R.sup.6 is D-Phe,where R.sup.6 is R*.sup.6,Q is a complexed metal-containing acyl group having the formula: ##STR1## wherein Q' is Pt(Y).sub.Type: GrantFiled: June 3, 1991Date of Patent: November 2, 1993Assignee: The Administrators of the Tulane Educational FundInventors: Andrew V. Schally, Sandor Bajusz
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Patent number: 5250295Abstract: A factor (NKEF) for use in enhancing the activity of natural killer cells both in vivo and in vitro. NKEF is a soluble red blood cell cytosol protein having a molecular mass of between about 300 and 400 kilodaltons as determined by gel filtration high pressure liquid chromatography and an apparent molecular weight of about 48 kilodaltons as determined by non-reducing SDS-PAGE.Type: GrantFiled: November 4, 1991Date of Patent: October 5, 1993Assignee: The Regents of the Univ. of CaliforniaInventors: Hungyi Shau, Sidney H. Golub
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Patent number: 5246846Abstract: Reactants containing amino, mercapto or hydroxy groups such as proteins, peptides, ligands, coenzymes or enzymes are immobilized on a support containing amino, mercapto or hydroxy groups by coupling the reactant to the support with a compound having the following formula (I) or (IA): ##STR1## wherein X is a halogen and R.sub.1, R.sub.2 are the same or different and are X, R, COR, COOR, wherein R is C.sub.1 -C.sub.8 alkyl, COOH, CNS, N.sub.3 or CN. The support may be first reacted with the compound to produce a derivatized support which is then reacted the reactant or the reactant may be first reacted with the compound and the resultant product then reacted with the support. An electrochemical biosensor can be prepared by using a conductive support.Type: GrantFiled: December 31, 1990Date of Patent: September 21, 1993Inventors: Fritz Pittner, Thomas Schalkhammer, Gerald Urban, Eva Mann-Buxbaum
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Patent number: 5244654Abstract: Internal polymeric surfaces of medical devices are provided that have enhanced biocompatibility properties. The internal polymeric surface presents an anti-thrombogenic, fibrinolytic or thrombolytic interface with body fluids such as blood flowing through medical device tubing during implantation for medical procedures. The biocompatibility enhancing agent is secured to the polymeric substrate by a spacer molecule which is covalently bound to the internal polymeric surface which had been subjected to radiofrequency plasma treatment with a low pressure plasma medium of water vapor, oxygen or combination of water vapor and oxygen gas.Type: GrantFiled: June 25, 1991Date of Patent: September 14, 1993Assignee: Cordis CorporationInventor: Pallassana V. Narayanan
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Patent number: 5243028Abstract: The present invention relates to a series of novel silicone proteins which are high substantive to fiber and hair. They are cationic materials which contain an ester linkage. A chloroester of a dimethicone copolyol is reacted with the amino group of a protein or amino acid. The compounds contain both a silicone portion and protein portion in a covalent bone one molecule. Since the compounds of the present invention are high molecular weight silicone polymers, they have a high degree of oxidative stability, even at elevated temperatures and are nonirritating to skin and eyes. The proteins of the present invention plate out on and form a film on the surface of hair skin and textile fibers. In addition, these compounds are non volatile and exhibit a inverse cloud point. These combination of properties makes these polymers ideally suited for use in personal care applications.Type: GrantFiled: March 16, 1992Date of Patent: September 7, 1993Assignee: Siltech CorporationInventor: Anthony J. O'Lenick, Jr.
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Patent number: 5234820Abstract: An auxiliary substance such as a label, support, or bioactive agent is attached to a protein at a site that is remote from the active site of the protein by the use of exopeptidase and a nucleophile which is an amino acid, amino acid derivative, amine or alcohol. In one embodiment, the nucleophile is attached to the carboxy terminus of a protein by catalysis with exopeptidase to form an adduct and then the adduct or its combination with a linker arm is bound to the auxiliary substance. In another embodiment, the auxiliary substance or its combination with a linker arm is bound to the nucleophile to form an intermediate substance which is then coupled by catalysis with exopeptidase to the carboxy terminus of a protein.Type: GrantFiled: June 28, 1990Date of Patent: August 10, 1993Assignees: Board of Regents of the University of Nebraska, BioNebraska, Inc.Inventors: Fred W. Wagner, Thomas R. Coolidge, Sheldon M. Schuster, Jay Stout, Dwane E. Wylie, Klaus Breddam, William Lewis
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Patent number: 5219926Abstract: A process for covalently bonding biopolymer, such as protein, to an organic polymer surface coated with hydrophilic nonionic polymer having groups reactive with the biopolymer and having a cloud point in the reaction medium that is at least 5.degree. C. above the temperature at which the coated organic polymer surface is to be used, which comprises reacting biopolymer with the surface in an aqueous reaction medium, at a temperature not less than 5.degree. C. below the cloud point; but not above a temperature at which the biopolymer is deleteriously affected, and preferably not above about 100.degree. C., the product comprises a biopolymer immobilized on a hydrophilic solid surface having a nonionic polymer and a hydrophilic layer, coupled thereto via biopolymer-reactive groups of the nonionic polymer, and accordingly has low spontaneous adsorption of proteins and other biopolymers through electrostatic attraction and/or hydrophobic interaction.Type: GrantFiled: September 13, 1991Date of Patent: June 15, 1993Assignee: Berol Nobel ABInventors: Bjorn Lindman, Martin Malmsten, Krister Holmberg, Carina Andren
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Patent number: 5196478Abstract: This invention relates to radio-derivatized polymers and a method of producing them by contacting non-polymerizable conjugands with radiolysable polymers in the presence of irradiation. The resulting radio-derivatized polymers can be further linked with ligands of organic or inorganic nature to immobilize such ligands.Type: GrantFiled: April 9, 1990Date of Patent: March 23, 1993Assignee: Epipharm Allergie-Service Gesellschaft m.b.H.Inventors: Janos M. Varga, Peter Fritsch
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Patent number: 5194300Abstract: Highly fluorescent latex microspheres have a diameter of less than five hundred angstroms and have more than five thousand fluorescent markers per sphere. The microspheres are prepared by reacting an acrylic latex bead with a diamine and a fluorescent amine at elevated pH. A protein such as avidin or an immunoglobulin may then be conjugated to the diamine. A single fluorescent microsphere is visible using standard fluorescent microscopy. Therefore the microspheres may be utilized not only to visualize cell surface anitgens but also DNA encoding for single genes, by means of a biotinylated DNA probe.Type: GrantFiled: November 8, 1989Date of Patent: March 16, 1993Inventor: Sau W. Cheung
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Patent number: 5182317Abstract: The present invention is directed to multifunctional thrombo-resistant coatings for use with biomedical devices and implants, such as a coating which includes a siloxane surface onto which a plurality of amine functional groups have been bonded. Covalently bonded to the amine functional groups are a plurality of poly(ethylene oxide) chains, such that a single poly(ethylene oxide) chain is bonded to a single amine functional group. A plurality of different bioactive molecules, designed to counteract specific blood-material incompatibility reactions, are covalently bonded to poly(ethylene oxide) chains, such that a single bioactive molecule is coupled to a single polyethylene oxide chain. The method of manufacturing the present invention include preparing a material having a siloxane surface onto which a plurality of amine functional groups have been bonded. This is achieved by plasma etching with ammonia gas or by plasma polymerization of a siloxane monomer in the presence of ammonia gas.Type: GrantFiled: June 17, 1991Date of Patent: January 26, 1993Assignee: Cardiopulmonics, Inc.Inventors: Suzanne Winters, Kenneth A. Solen, Clifton G. Sanders, J. D. Mortensen, Gaylord Berry
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Patent number: 5168057Abstract: A trifunctional conjugate is provided having three chemical moieties, attached through a spacer moiety. At least two of the chemical moieties are relatively small molecules, usually less than about 7,000 Daltons in size. The spacer moiety is selected to impart certain steric properties to the conjugate. In one embodiment, the binding of a macromolecular specific binding partner to one of the chemical mouths sterically inhibits the binding of a different macromolecule to another chemical moiety. In another embodiment, the binding of a first chemical moiety to a macromolecule restricts the subsequent binding of a second chemical moiety to a proximate location on the same macromolecule.Type: GrantFiled: September 30, 1991Date of Patent: December 1, 1992Assignee: Beckman Instruments, Inc.Inventors: Chan S. Oh, James C. Sternberg
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Patent number: 5155166Abstract: Useful materials for diagnostic tests, affinity chromatography, enzymatic reactions and immunoassays are prepared by covalently attaching reactive compounds containing reactive amino or sulfhydryl groups to polymeric particles having pendant carboxyl groups on the outer surfaces. Such reactive compounds include biologically reactive species, including enzymes, polypeptides and proteins. This attachment is carried out using specific carbamoylonium compounds, namely certain 1-(1-pyrrolidinylcarbonyl)pyridinium salts. These compounds react with the carboxyl groups on the particles to form intermediate reactive groups which then react with the amino or sulfhydryl groups to form a covalent linkage between particle and reactive compound. A kit comprises polymeric particles having carboxyl groups on the outer surfaces, and a 1-(1-pyrrolidinylcarbonyl)pyridinium salt.Type: GrantFiled: June 18, 1990Date of Patent: October 13, 1992Assignee: Eastman Kodak CompanyInventors: Susan J. Danielson, Donald P. Specht
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Patent number: 5153166Abstract: Methods for modifying polyhydroxylated materials by the direct covalent bonding of nucleophilic ligands to the former sites of hydroxyl groups on the material are disclosed. More specifically, methods for activating the surface of polyhydroxylated materials such as silica, which can serve as stationary phases in various chromatographic methods, are disclosed. The silica is first contacted with a reagent, e.g., a phosphorylating agent, effective to cleave the O--H bond of at least one of said hydroxyl groups and introduce through an --O-- linkage a moiety amenable to nucleophilic displacement; and the product of step (a) is then contacted with a suitable nucleophilic ligand.Type: GrantFiled: August 18, 1988Date of Patent: October 6, 1992Assignee: Trustees of AT BiochemInventors: Tikam Jain, Robert Shorr
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Patent number: 5141648Abstract: The present invention provides cleavable conjugates whose linkers contain a labile bond that is cleavable under a variety of mild conditions, including weakly acidic. Since the agent may be bonded directly to the linker, cleavage can result in release of native agent. The invention also provides methods for producing cleavable conjugates. Preferred agents include drugs, toxins, biological response modifiers, radiodiagnostic compounds, radiotherapeutic compounds, and derivatives thereof. The targeting molecule employed in the invention may be an intact molecule, a fragment thereof, or a functional equivalent thereof. In a particularly preferred embodiment, the targeting molecule is a monoclonal antibody directed towards a tumor-associated antigen in man. The invention further provides methods for delivering to the cytoplasm of a target cell an agent free of its targeting molecule carrier.Type: GrantFiled: March 29, 1991Date of Patent: August 25, 1992Assignee: NeoRx CorporationInventors: Mark D. Hylarides, Ananthachari Srinivasan, Jeffrey N. Fitzner, Vivekananda M. Vrudhula
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Patent number: 5122450Abstract: A biochemical reagent comprises an oligosaccharide, preferably one which has been liberated from an immunogenic glycoprotein or proteoglycan, which is immobilized on a carrier via an intermediate spacer molecule such as a lipid. The lipid molecule should preferably have at least two long lipid tails so that the oligosaccharide is held in spaced relationship to the carrier where is exhibits antibody-binding ability which is almost indistinguishable from that of the original glycoprotein or proteoglycan. The reagent has its application in biochemical testing of oligosaccharides and systems which bind to them.Type: GrantFiled: August 20, 1987Date of Patent: June 16, 1992Assignee: Research Corporation LimitedInventors: Ten Feizi, Ping W. Tang
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Patent number: 5102798Abstract: Langmuir-Blodgett films having hydrophobic surfaces are chemically modified to convert the hydrophobic surfaces to hydrophilic surfaces for immobilization of active moieties having bioactive, immunoactive, thermoactive, electroactive, optoactive or redoxactive properties. Langmuir-Blodgett films having a hydrophobic surface of omega unsaturated covalent bonds are formed from an amphiphilic, bifunctional surface active material having a hydrophobic tail group bearing an omega terminus of double or triple bonded unsaturation. The amphiphilic material may be fatty acids, phospholipids or porphyrins, and is preferably omega-tricosenoylamide or omega-tricosenoic acid. Chemical modification is carried out by exposing the hydrophobic surface to a reagent such as alkaline or acidic potassium permanganate, potassium dichromate or osmium tetroxide which oxidizes the omega unsaturated covalent bonds to provide hydrophilic groups such as hydroxyl or carboxylic acid groups.Type: GrantFiled: September 8, 1988Date of Patent: April 7, 1992Assignee: Allage AssociatesInventor: Anthony Guiseppi-Elie
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Patent number: 5100668Abstract: A system for stabilizing fibroblast-derived growth factors, maintaining their bioactivity over a prolonged period of time and controllably releasing them for use is disclosed. The system uses growth factors bound to biocompatible substrates via heparin or heparin derived compounds to maintain the bioactivity of the growth factors. A growth factor bound to a heparin coated substrate can be used independently as a controlled release device, or can be incorporated into a reservoir or matrix type controlled release devices to further enhance the controlled release properties. The stabilized growth factors can be implanted into a patient, thereby providing a means for producing an in vivo controlled release of a growth factor to the patient.Type: GrantFiled: June 14, 1988Date of Patent: March 31, 1992Assignee: Massachusetts Institute of TechnologyInventors: Elazer R. Edelman, Robert S. Langer, Michael Klagsburn, Edith Mathiowitz
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Patent number: 5091176Abstract: Biocompatible polymers derived from isocyanate-capped high molecular weight triols and higher polyols are covalently linked to drugs. These polymer-modified drugs have one or more of the following advantages over the unmodified drug: reduction of immunogenicity of the drug, increased circulating half-life of the drug due to longer residence time in circulation, ability to administer multiple drugs together, and enhanced potency of the drug.Type: GrantFiled: April 24, 1990Date of Patent: February 25, 1992Assignee: W. R. Grace & Co.-Conn.Inventors: James A. Braatz, Aaron H. Heifetz
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Patent number: 5089605Abstract: The invention concerns unique immobilized immunoglobulin-binding protein materials which have a high binding capacity for immunoglobulins. Exemplified are preparations which have a high binding capacity for IgGl immunoglobulins. The preparations are made by covalently joining an immobilization support material to (a) an arginine-containing linker and (b) an immunoglobulin-binding protein material. The immunoglobulin-binding protein can be joined to the linker through an amide bond. Specifically disclosed is an immobilized protein A preparation. This immobilized protein A preparation has utility in the art of purifying monoclonal antibodies.Type: GrantFiled: March 13, 1987Date of Patent: February 18, 1992Assignee: Repligen CorporationInventors: Albert T. Profy, Margaret A. Belew, Walter C. Herlihy
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Patent number: 5079155Abstract: A solid support useful for bioaffinity and ion-exchange separations and enzyme immobilization is provided. The support is based on a non-perfluorocarbon solid carrier core coated with a nonionic fluorosurfactant-coated fluorocarbon interlayer to which a ligand or a binder for the ligand is securely, but reversibly attached through a reactive perfluorocarbon anchor compound. Also provided is a solid support useful for size exclusion separations. Such support is based on a non-perfluorocarbon carrier core coated with a nonionic fluorosurfactant-coated fluorocarbon interlayer.Type: GrantFiled: September 28, 1989Date of Patent: January 7, 1992Assignee: E. I. du Pont de Nemours and CompanyInventors: Geoffrey B. Cox, Robert K. Kobos
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Patent number: 5077210Abstract: Active agents such as proteins are covalently immobilized on substrates carrying hydroxyl groups. A silane is bound to the substrate and coupled to a heterobifunctional crosslinker at one functional group leaving a free functional group, different than the first group, to which a protein is bound while retaining high protein functionality. Preferably, the silane has a functional group which reacts with the hydroxyl group of the substrate and a thiol terminal group which reacts with a functional group of a heterobifunctional crosslinking agent which contains a succinimide group that reacts with an amino group of the active agent. Bound active agents such as proteins are useful as biosensors or reactants in a variety of applications including bioassays.Type: GrantFiled: January 13, 1989Date of Patent: December 31, 1991Inventors: Frances S. Eigler, Jacque Georger, Suresh K. Bhatia, Jeff Calvert, Lisa C. Shriver-Lake, Reinhard Bredehorst
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Patent number: 5071651Abstract: Immunological carrier complexes are provided utilizing the VP6 polypeptide from rotavirus as the carrier molecule. Also provided are methods of binding epitope-bearing molecules (e.g., haptens) to the VP6 carrier molecule through binding peptides. The VP6 carrier can be a VP6 monomer, oligomer, or a particle containing of VP6 oligomers.Type: GrantFiled: March 5, 1990Date of Patent: December 10, 1991Assignee: University of SaskatchewanInventors: Marta I. Sabara, Patrick J. Frenchick, Kerry F. Mullin-Ready
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Patent number: 5055558Abstract: A method for the selective extraction of beta-lactoglobulin and other proteins from whey or milk by means of subunit exchange chromatography and for the deproteinization of whey by subsequent chromatography on an ion exchange resin.Type: GrantFiled: March 25, 1988Date of Patent: October 8, 1991Assignee: Consiglio Nazionale Della RicercheInventors: Emilia Chiancone, Maurizio Gattoni
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Patent number: 5053453Abstract: Thromboresistant materials are disclosed comprising hirudin or hirudin derivatives covalently linked to support materials such that the resultant composition has substantially the same biological activity as hirudin. Methods for making such compositions are also disclosed.Type: GrantFiled: January 15, 1991Date of Patent: October 1, 1991Assignee: Baxter International Inc.Inventor: Cecilia S. L. Ku
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Patent number: 5043278Abstract: Fixation of a physiologically active substance on a carrier through an alkylene oxide chain allows the physioactive function of the substance to be retained to a high degree. The fixed physiologically-active substances are useful for separation and purification of materials. The carrier is preferably a thin fiber of 1.0 denier or less, and may be formed from a polymer. The alkylene oxide chain has an amino or epoxy group at one end which bonds to the carrier and a functional group at the other end which bonds to a physiologically-active substance.The carrier is preferably a thin fiber of 1.0 denier or less, and may be formed from a polymer. The alkylene oxide chain has an amino or epoxy group at one end which bonds to the carrier and a functional group at the other end which bonds to a physiologically-active substance.Type: GrantFiled: July 6, 1990Date of Patent: August 27, 1991Assignee: Toray Industries, Inc.Inventors: Shoji Nagaoka, Hajimu Kurumatani, Yuichi Mori
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Patent number: 5037883Abstract: A polymeric drug comprising an inert synthetic polymeric carrier combined through aminoacid or peptide spacers with a bioactive molecule, a targeting moiety, and an optional cross-linkage, comprises:(a) 5.0 to 99.7 mol % of units derived from N-(2-hydroxypropyl)methacrylamide,(b) 0.2 to 20.0 mol % of units derived from an N-methylacrylcylated peptide, the peptide groups being bound to a bioactive moiety,(c) 0.1 to 94.8 mol % of units derived from N-methacrylamide, N-methacrylic acid or an N-methacrylolated aminoacid or peptide, to which are bound a determinant capable of interacting with specific receptors on cell surfaces,(d) optionally, 0 to 5 mol % of units derived from an N-methacryloylated peptide, the peptide groups being bound to a linking group which is similarly to a similar peptide group attached to another polymer chain, and(e) optionally, as a bioassay label, 0 to 2 mol % units derived from N-methyacryloylated tyrosinamide.Type: GrantFiled: November 17, 1989Date of Patent: August 6, 1991Assignees: Ceskoslovenska Akademie Ved, Carlton Medical Products LimitedInventors: Jindrich Kopecek, Pavla Rejmanova, Jiri Strohalm, Karel Ulbrich, Blanka Rihova, Vladimir Chytry, John B. Lloyd, Ruth Duncan
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Patent number: 4997758Abstract: Stable cross-linked complexes of transition-metal tetracarboxylates and proteins are formed. The preferred transition-metal is rhodium. The protein may be collagen or an enzyme such as a proteolytic enzyme.Type: GrantFiled: January 17, 1989Date of Patent: March 5, 1991Assignee: Iowa State University Research Foundation, Inc.Inventors: Nenad M. Kostic, Jian Chen
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Patent number: 4981961Abstract: A novel class of compounds, methods for the preparation thereof and the use thereof in chromatographic methods for binding various biologically active materials non-covalently are disclosed. The class of compounds comprises the reaction product of a polymeric gel with a pyridine base, such as 4-dimethylaminopyridine (DMAP), and a halogen-substituted pyridine, such as 3,5-dichloro-2,4,6-trifluoropyridine (DCTFP), which reaction product may in turn be optionally reacted with hydroxyl ions or specified low-molecular-weight compounds. These compounds are capable of selectively and efficiently binding proteins and other organic materials of interest non-covalently to a degree comparable or superior to the heretofore preferred natural affinity ligands, such as Protein A gels. The novel compounds find particular utility in purification and recovery of proteins such as serum albumin and immunoglobulins of various classes from crude sources, such as diluted serum samples from various species.Type: GrantFiled: September 8, 1989Date of Patent: January 1, 1991Assignee: BioProbe International, Inc.Inventor: That T. Ngo
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Patent number: 4954444Abstract: A bioaffinity separation method is provided along with a solid affinity support utilized in that method. Additionally, immobilized enzyme systems are provided for use as enzyme electrode systems. The support is based on an inert perfluorocarbon polymer carrier with ligands or binders attached to its surface through a highly fluorinated isocyanate anchor group. Methods for preparing such supports and their use in capturing target molecules from samples and in analytical applications are also provided.Type: GrantFiled: December 17, 1987Date of Patent: September 4, 1990Assignee: E. I. Du Pont de Nemours and CompanyInventors: John William d. Eveleigh, Robert K. Kobos
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Patent number: 4948836Abstract: Antibodies which are immobilized and covalently bound to a matrix polymer by means of a modification in a carbohydrate region of the antibodies; wherein the binding of the antibodies is effected by condensing at least one aldehyde group in an oxidized carbohydrate region and at least one epoxide function of an epoxy-group-containing matrix polymer, said condensation being conducted in the presence of a bifunctional reagent which has, on one end position of a spacer unit having at least three members, an amino group capable of condensing with the aldehyde group, and which has on the other end position a group which reacts covalently with the epoxide function.Type: GrantFiled: November 14, 1988Date of Patent: August 14, 1990Assignee: Roehm GmbH Chemische FabrikInventors: Beka Solomon, Eran Hadas, Gideon Fleminger
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Patent number: 4933285Abstract: The present invention provides a process for building an immobilized structure comprising multiple monolayers of effective sequential polymeric linkages. The multiple monolayers are built, monolayer by monolayer, from the surface of a solid phase, by an alternating reaction sequence conducted with multifunctional reagents. The process provides the capability of building numerous immobilized multiple monolayer structures wherein the length of each structure extending from a solid phase is substantially the same. Structures comprising multiple monolayers of polymeric linkages are useful for many purposes, as for example, immobilizing macromolecules or other biomolecules and the like to produce chemical or biochemical sensors. Other uses extend to molecular electronic applications, such as the production of molecular conductive wires and molecular circuitry.Type: GrantFiled: December 21, 1988Date of Patent: June 12, 1990Assignee: Environmental Technologies Group, Inc.Inventor: Jesse C. Patton
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Patent number: 4891219Abstract: This invention relates to a method for the active or passive immunization of a vertebrate against ectoparasites and endoparasites, and a method of treating a vertebrate host infected by ectoparasites or endoparasites, comprising administering to the vertebrate an immunogen comprising one or more endocrine products of ectoparasites and endoparasites, coupled with an immunogenic carrier, or administering to the vertebrate, monoclonal antibodies capable of binding to the native form of the endocrine product.Type: GrantFiled: September 14, 1987Date of Patent: January 2, 1990Assignee: Aphton CorporationInventors: Stephen L. Karr, Jr., Elizer Benjamini, Robert J. Scibienski, Stephen Grimes
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Patent number: 4886755Abstract: Thiol gels are prepared from hydroxyl containing polymers by forming a 2-fluoro-1-methylpyridoxy derivative of the polymer followed by reacting the derivative with sodium dimethyldithiocarbamate and reducing to produce a sulfhydryl substituted polymer. Alternatively, the derivative is reacted with dithiothreitol to produce a sulfhydryl substituted polymer having free sulfhydryl groups spaced from the polymer. The thiol gel can be activated by means of 2,2'-dipyridyl disulfide and reacted with a free sulfhydryl containing biologically active ligand in order to provide an insolubilized ligand which can be used for various purposes including use as an immobilized biologically active material or use as a matrix in covalent chromatography.Type: GrantFiled: October 13, 1987Date of Patent: December 12, 1989Assignee: Bioprobe International, Inc.Inventor: That T. Ngo
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Patent number: 4885250Abstract: A bioaffinity separation method is provided along with a solid affinity support utilized in that method. Additionally, immobilized enzyme systems are provided for use as enzyme electrode systems. The support is based on an inert perfluorocarbon polymer carrier with ligands or binders attached to its surface. The ligand, binder or enzyme is preferably modified by attaching a perfluorocarbon anchor group, and the modified ligand, binder or enzyme is attached to the carrier through the anchor group. Methods for preparing such supports and their use in capturing target molecules from samples and in analytical applications are also provided.Type: GrantFiled: March 2, 1987Date of Patent: December 5, 1989Assignee: E. I. Du Pont De Nemours and CompanyInventors: John William d. Eveleigh, Robert K. Kobos
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Patent number: 4874813Abstract: A biological composition comprises a solid phase support matrix or marker molecule bound to protein, typically a glycoprotein such as an immunoglobulin through a linking group, spacer arm, and hydrazone group. The linking group is conveniently an ether linkage, while the spacer arm is a linear chain including six atoms, where at least one of the atoms is a tertiary amine which is protonated at a pH below about 8. The hydrazone is formed by reacting the solid phase or marker molecule having the linking arm and the spacer arm including a terminal hydrazide group with a glycoprotein oxidized to include a terminal aldehyde group. Immunological reagents prepared by linking an immunoglobulin (IgG) through a carbohydrate on the Fc or hinge regions have been found to provide very high binding capacity approaching the theoretical bivalent limit of two moles of bound antigen for every mole of bound immunoglobulin.Type: GrantFiled: February 9, 1987Date of Patent: October 17, 1989Inventor: Daniel J. O'Shannessy