Attached To The Carrier Via A Bridging Agent Patents (Class 435/181)
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Patent number: 5229284Abstract: Enzymes are immboilized on an inorganic carrier which is a round, macropermeable agglomerate having a mulberry-type structure formed from spherical microporous .alpha.-aluminum oxide hydroxide particles. An organic polycondensate having free organic functional groups as enzyme binding sites penetrates the agglomerate. The .alpha.-aluminum oxide hydroxide particles of the agglomerate retain essentially their form prior to agglomeration. The polycondensate is prepared by reacting a polyimine with a dialdehyde or an epoxy compound. Preferably, the polyimine is polyethyleneimine, the dialdehyde is glutardialdehyde and the epoxy compound is an epoxy-functional silicon resin, an aliphatic diepoxide or an aliphatic triepoxide. The agglomerate is prepared by granulating the .alpha.-aluminum oxide hydroxide particles in the presence of the polyimine to form the agglomerate having the polyimine dispersed throughout and then reacting the polyimine with the dialdehyde or the epoxy compound.Type: GrantFiled: July 30, 1991Date of Patent: July 20, 1993Assignee: Kali Chemie AGInventors: Dirk Bonse, Hubert Schindler, Hans-Joerg Mueller
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Patent number: 5221771Abstract: Macromolecular species such as enzymes, proteins, drugs, and solid supports which contain reactive carbonyl groups or groups which are readily converted to reactive carbonyl groups are modified by reaction with a compound of the formula ##STR1## in which R.sup.1 is H, C.sub.1 -C.sub.20 alkyl, phenyl, (C.sub.1 -C.sub.10 alkyl)-substituted phenyl, or phenyl-substituted C.sub.1 -C.sub.10 alkyl; R.sup.2 is C.sub.2 -C.sub.5 alkylene or (C.sub.1 -C.sub.4 alkoxy)-substituted C.sub.2 -C.sub.5 alkylene; R.sup.3 is ##STR2## R.sup.4 is H or C.sub.1 -C.sub.4 alkyl; n is at least 5; and m is zero or 1.Type: GrantFiled: July 15, 1992Date of Patent: June 22, 1993Assignee: Xoma CorporationInventors: Dayton T. Reardan, Dane A. Goff
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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: 5217492Abstract: A long chain chemical spacer useful for attaching a biomolecule to a support having a hydrophobic surface, the spacer having a hydrophobic guiding group capable of becoming embedded in the surface, and optionally including a stopping group and/or an attached biomolecule.Type: GrantFiled: April 3, 1991Date of Patent: June 8, 1993Assignee: Bio-Metric Systems, Inc.Inventors: Patrick Guire, Shawn G. Dunkirk
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Patent number: 5200270Abstract: A carrier for a biologically active component for immunoassay or enzymatic reaction, which comprises:a) a thermoplastic resin bead having an average diameter of from 0.05 to 20 mm,b) from 1 to 25% by weight, based on the bead, of a magnetically responsive powder bonded to the bead, andc) a polymer coated thereon in a thickness of from 2 to 30 .mu.m, said polymer having a number average molecular weight of from 200 to 10,000 and having functional groups capable of binding, or being activated to bind, the biologically active component.Type: GrantFiled: September 19, 1991Date of Patent: April 6, 1993Assignee: Toyo Soda Manufacturing Co., Ltd.Inventors: Hiroshi Ishida, Yuji Higo, Masuo Inoue
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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: 5192507Abstract: A method of immobilizing and stabilizing an active biological receptor in a polymeric film and receptor-based biosensors for determining an analyte of interest in a sample. The receptor-based biosensors include a polymeric film having a biological receptor capable of binding an analyte of interest immobilized therein according to the method of the present invention and an electrical means for determining the presence and quantity of the analyte. In particular, acetylcholine receptor and opiate receptor have been immobilized in a polymeric film made by combining the receptor, a material (e.g., bovine serum albumin, gelatin) capable of polymerizing and a polymerizing agent (e.g., glutaradehyde).Type: GrantFiled: March 4, 1991Date of Patent: March 9, 1993Assignee: Arthur D. Little, Inc.Inventors: Richard F. Taylor, Ingrid G. Marenchic, Edward J. Cook
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Patent number: 5190864Abstract: A method for amplifying enzyme activity is disclosed. Enzyme amplification is achieved by covalently bonding enzyme to a supporting material via a molecular chain which is a substrate for the enzyme, then introducing a small amount of enzyme in the free state to this system, causing release of a large amount of bound enzyme. In an alternative embodiment, complementary enzymatically inactive fragments of an active enzyme, which fragments can recombine to form active enzyme, are covalently attached to separate support materials by a molecular chain material which is a substrate for the active enzyme, and these two fragment-supported conjugates are connected in series. Upon application of free enzyme or free complementary enzyme to one of these fragment-support conjugates, followed by application of the resulting product mixture to the second fragment-support conjugate, a large amount of free enzyme is ultimately produced.Type: GrantFiled: April 30, 1990Date of Patent: March 2, 1993Assignee: Northeastern UniversityInventors: Roger W. Giese, Markus Ehrat, Douglas J. Cecchini
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Patent number: 5182201Abstract: A support matrix particularly suitable for the immobilization of biologically active materials acting on lipophilic substrates results from the reaction of a polyamine-impregnated porous particle with a monofunctional paraffinic aldehyde. The resulting support matrix has a hydrophobic coating providing a microenvironment for the biologically active material, such as an enzyme, and hydrophilic portions for emulsification or binding to polar regions at or near the active site.Type: GrantFiled: October 26, 1990Date of Patent: January 26, 1993Assignee: UOPInventor: Yoshihisa Tsuda
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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: 5158880Abstract: A process for preparing solid perfluorocarbon polymer supports permitting uniform and secure attachment of perfluorocarbon-substituted ligands or binders to carriers is provided utilizing pretreatment of the carriers with water miscible organic solvents.Type: GrantFiled: September 23, 1988Date of Patent: October 27, 1992Assignee: E. I. Du Pont de Nemours and CompanyInventor: John W. D. Eveleigh
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Patent number: 5157099Abstract: Macromolecular species such as enzymes, proteins, drugs, and solid supports which contain reactive carbonyl, groups or groups which are readily converted to reactive carbonyl groups are modified by reaction with a compound of the formula ##STR1## in which R.sup.1 is H, C.sub.1 -C.sub.20 alkyl, phenyl, (C.sub.1 -C.sub.10 alkyl)-substituted phenyl, or phenyl-substituted C.sub.1 -C.sub.10 alkyl; R.sup.2 is C.sub.2 -C.sub.5 alkylene or (C.sub.1 -C.sub.4 alkoxy)-substituted C.sub.2 -C.sub.5 alkylene; R.sup.3 is ##STR2## R.sup.4 is H or C.sub.1 -C.sub.4 alkyl; n is at least 5; and m is zero or 1.Type: GrantFiled: December 12, 1991Date of Patent: October 20, 1992Assignee: Xoma CorporationInventors: Dayton T. Reardan, Dane A. Goff
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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: 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: 5139881Abstract: A process for surface modifying a variety of polymeric support surfaces is disclosed in which a predetermined modifying polymer is irreversibly absorbed onto essentially all the surfaces of the support polymer accessible to the modifying polymer. The modifying polymer is selected to impart the desired surface characteristics to the modified polymeric surface.Type: GrantFiled: November 17, 1988Date of Patent: August 18, 1992Assignee: Monsanto CompanyInventors: Jay M. Henis, Mary K. Tripodi, Donald I. Stimpson
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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: 5122456Abstract: A method is disclosed for the quantitative determination of 1,4-dihydronicotinamide adenisne dinucleotide (NADH) in solution. The method comprises contacting the NADH-containing solution with an activated carbon electrode, maintaining the carbon electrode at a controlled, fixed potential effective to cause oxidation of NADH at the electrode surface, and measuring the current output from the carbon electrode, wherein there is used a noble metal containing preferably a platinized or palladized activated carbon electrode comprising a porous, heterogeneous, resin-bonded layer of activated carbon or graphite particles comprising the finely divided noble metal preadsorbed thereon and bonded together with a natural or synthetic resin binder, preferably a hydrophobic resin such as polytetrafluoroethylene.Type: GrantFiled: February 24, 1989Date of Patent: June 16, 1992Assignee: Cambridge Life Science plcInventors: Hugh P. Bennetto, Gerard M. Delaney, Jeremy R. Mason, Christopher F. Thurston, John L. Stirling, David R. DeKeyzer, William H. Mullen
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Patent number: 5116733Abstract: Disclosed is a method of assaying a target substance. In the method of the present invention, a complex of the target substance and a substance labelled with peroxidase is fixed to a hydrophobic membrane. Then hydrogen peroxide, an aromatic primary amine and a phenolic compound are contacted with the peroxidase on the membrane to generate and deposit color on the hydrophobic membrane. The deposited color is then measured so as to assay the target substance.Type: GrantFiled: August 22, 1989Date of Patent: May 26, 1992Assignee: Konica CorporationInventor: Masahiko Yamasaki
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Patent number: 5108576Abstract: A device for detecting the presence of a predetermined reactant in a fluid suspected of containing the same which comprises a pyroelectric film having a first and a second surface, a first electrode in contact with a portion of the first surface of said pyroelectric film, a second electrode in contact with a portion of the first surface of said pyroelectric film, said first and said second electrodes being proximate to but electrically insulated from each other, an infra-red transparent third electrode having a first and second surface, said first surface being in contact with the second surface of said film, methods of making such a device and methods of utilizing same.Type: GrantFiled: June 13, 1988Date of Patent: April 28, 1992Assignee: Ohmicron CorporationInventors: Mark K. Malmros, Julian Gulbinski, III, William S. Collins, William Gibbs
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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: 5080891Abstract: A biologically persistent, water-soluble, substantially non-immunogenic, substantially non-antigenic conjugate of superoxide dismutase is prepared by coupling one to five strands of a polyalkylene glycol which is polyethylene glycol or polyethylene-polypropylene glycol copolymer, wherein said polyalkylene glycol has an average molecular weight of about 35,000-1,000,000.Type: GrantFiled: August 1, 1990Date of Patent: January 14, 1992Assignee: DDI Pharmaceuticals, Inc.Inventors: Mark Saifer, Ralph Somack, L. David Williams
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Patent number: 5079156Abstract: The invention relates to crosslinked polymers based on polyvinyl acylate or polyvinyl alcohol and having crosslinking agent units which are derived from crosslinking agents of the general formulae ##STR1## These products, inter alia, are particularly hydrolysis-resistant and can have high crosslinking densities.The invention also relates to a process for preparing these polymers and to their use in chromatography and as carriers for biologically active substances.Type: GrantFiled: August 31, 1988Date of Patent: January 7, 1992Assignee: Hoechst AktiengesellschaftInventors: Otto Mauz, Siegfried Noetzel, Bernhard Neumann
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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: 5063109Abstract: Novel methods for covalent attachment of antibodies, antigens, or other molecules to solid phases using extended length heterobifunctional crosslinking reagents are disclosed. The resulting derivatized solid phases can be used in diagnostic assays.Type: GrantFiled: September 1, 1989Date of Patent: November 5, 1991Assignee: Abbott LaboratoriesInventors: Christopher Bieniarz, J. Christopher Welch, Grady Barnes, Carol A. Schlesinger
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Patent number: 5049494Abstract: An economical method of converting mannose to fructose uses a mannose isomerase from Pseudomonas cepacia immobilized on an alumina containing polyethyleneimine crosslinked with an excess of glutaraldehyde. The method utilizes mannose-containing aqueous solutions as the feedstock, and affords solutions in which at least 55% of the mannose has been converted to fructose. Because of the relatively higher levels of fructose than can be obtained by isomerizing glucose to fructose using glucose isomerase, substantial savings in separation of high fructose-containing products can be achieved. The process described represents the first economical mannose isomerase process.Type: GrantFiled: February 8, 1989Date of Patent: September 17, 1991Assignee: Allied-Signal Inc.Inventor: Paul Allenza
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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: 5041385Abstract: Fusion proteins comprising a first amino acid sequence and a second amino acid sequence are disclosed. The first amino acid sequence is derived from a retrotransposon or an RNA retrovirus and confers on the fusion protein the ability to assemble into particles. The TYA gene of the yeast retrotransposon Ty codes for the first amino acid sequence. The second amino acid sequence is a biologically active antigen. The particles formed by the fusion proteins are useful in vaccines or in diagnostic or purification applications.Type: GrantFiled: April 10, 1987Date of Patent: August 20, 1991Assignee: Oxford Gene Systems LimitedInventors: Alan J. Kingsman, Susan M. Kingsman, Sally E. Adams, Michael H. Malim, Elizabeth-Jane C. Mellor
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Patent number: 5028657Abstract: The present invention relates to a method of immobilizing proteins on a polymeric matrix by means of plasma activation and an apparatus and process for the use of such material. The protein mixture is applied to the surface of the polymeric matrix with or without the addition of a crosslinking agent. If is then placed into a plasma generator, wherein the functional groups on both the protein and the matrix molecules are activated to form free radicals. Upon returning from their high energy state, the free radicals form covalent bonds between the proteins and between the protein and the polymeric matrix. Using this method, the proteins are nonspecifically immobilized on the surface of the polymeric matrix. The method can be utilized to immobilize proteins on the surface of polymeric membranes, polymeric beads, polymeric tubes and polymeric plates. The immobilized protein has high biological activity and stability.Type: GrantFiled: July 18, 1988Date of Patent: July 2, 1991Assignee: Industrial Research Technology InstituteInventors: Tien-Tsai Hsu, Mann-Tchao Wang, Kuang-Pin Hsiung, Ging H. Hsiue, Min-Shyan Sheu
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Patent number: 5019521Abstract: Binding assay reagents for use in optical assay systems are disclosed. Assays, such as immunoassays, employing the reagent are also disclosed. The reagent is comprised of paired, associated polypeptides one of which has multiple optically active dye labels. The binding assay reagents exhibit enhanced binding activity over that of the dye labelled polypeptides alone and also enhance the sensitivity of the binding assay by providing increased amounts of optical label.Type: GrantFiled: March 12, 1990Date of Patent: May 28, 1991Assignee: Photest Diagnostics, Inc.Inventor: John Krupey
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Patent number: 5006333Abstract: A biologically persistent, water-soluble, substantially non-immunogenic, substantially non-antigenic conjugate of superoxide dismutase is prepared by coupling one to five strands of a polyalkylene glycol which is polyethylene glycol or polyethylene-polypropylene glycol copolymer, wherein said polyalkylene glycol has an average molecular weight of about 35,000-1,000,000.Type: GrantFiled: July 13, 1989Date of Patent: April 9, 1991Assignee: DDI Pharmaceuticals, Inc.Inventors: Mark Saifer, Ralph Somack, L. David Williams
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Patent number: 5002883Abstract: Novel methods for covalent attachment of antibodies, antigens, or other molecules to solid phases using extended length heterobifunctional crosslinking reagents are disclosed. The resulting derivatized solid phases can be used in diagnostic assays.Type: GrantFiled: October 11, 1988Date of Patent: March 26, 1991Assignee: Abbott LaboratoriesInventors: Christopher Bieniarz, Christopher J. Welch, Grady Barnes, Carol A. Schlesinger
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Patent number: 5002884Abstract: Physiologically active substances are immobilized on an inorganic support, by treating the inorganic support with an aminoalkylakoxysilane having the general formula(RO).sub.3 SiCH.sub.2 CH.sub.2 CH.sub.2 NH(CH.sub.2).sub.n NH.sub.2wherein, R is an alkyl group having 1 to 4 carbon atoms, and n is an integer having a value of 5 to 12, and chemically bonding a physiologically active substance by means of an amino group to the support.Type: GrantFiled: January 17, 1989Date of Patent: March 26, 1991Assignee: Toray Silicon Company, Ltd.Inventors: Hideki Kobayashi, Tadashi Matsunaga, Hideki Kobayashi
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Patent number: 5001062Abstract: An article adapted for applications where there is contact with blood and especially in medical applications is prepared by adsorbing the enzyme, lysozyme or derivative thereof, onto a substrate and then adsorbing heparin or a heparin-based material to the enzyme. The substrate is preferably a metal or polymeric material.Type: GrantFiled: November 14, 1988Date of Patent: March 19, 1991Assignee: Camurus ABInventors: Kare V. Larsson, Sven E. Bergentz, Bengt L. T. Lindblad
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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: 4994388Abstract: A microcarrier bead system for culturing anchorage-dependent cells is formed of a polystyrene core with a coating of collagen fixed thereover. In certain embodiments, the coating is a protein, such as laminin or fibronectin. The microcarrier bead is of low density, illustratively 1.02 g/cc, and therefore requires less agitation of the nutrient media to maintain suspension. This reduced stirring causes lower shear forces to impinge upon the cells, thereby improving the attachment and proliferation of the cells being cultured. The microcarrier bead of the present invention exhibits surprising advantages with respect to cell attachment and harvesting over beads formed entirely of collagen, or of DEAE-dextran coated with collagen. During harvesting, contamination of the product resulting from dissolved collagen, particularly when proteolytic enzymes are used, is minimized. Additionally, adsorption of toxins and product by the subject microcarrier beads is minimized.Type: GrantFiled: April 15, 1988Date of Patent: February 19, 1991Assignees: Solohill Engineering, Inc., The University of MichiganInventors: William J. Hillegas, James Varani, David L. Helmreich
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Patent number: 4983524Abstract: An enzyme is immobilized by contacting the enzyme with a support in a solution containing an iridoid aglycone cross-linking agent. The cross-linking agent may be genipin or an aglycone or an iridoid glycoside such as geniposide, gardenoside or geniposide acid.Type: GrantFiled: December 21, 1987Date of Patent: January 8, 1991Assignee: Suntory LimitedInventors: Shigeaki Fujikawa, Kunimasa Koga, Tomoko Yokota
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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: 4973493Abstract: A method for modifying the solid surface to improve its biocompatibility is disclosed. The method employs molecules of a biocompatible agent and a chemical linking moiety possessing a photochemically reactive group capable upon activation of covalently bonding to the solid surface and possessing a different reactive group as capable upon activation of covalently bonding to separate molecules of the biocompatible agent. The method comprises applying stimulus to sequentially activate the groups and covalently bind the different reactive group of the linking moiety to the molecules of the biocompatible agent and to photochemically covalently bind the linking moiety to the solid surface with a sufficient population density to enable the molecules of the biocompatible agent to effectively shield the solid surface and to provide a biocompatible surface.Type: GrantFiled: October 15, 1987Date of Patent: November 27, 1990Assignee: Bio-Metric Systems, Inc.Inventor: Patrick E. Guire
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Patent number: 4970145Abstract: Enzyme electrodes are disclosed which are capable of responding amperometrically to the catalytic activity of the enzyme in the presence of its respective substrate and comprising the enzyme immobilized or adsorbed onto the surface of an electrically conductive support member which consists of or comprises a porous layer of resin-bonded carbon or graphite particles, said particles having intimately mixed therewith, or deposited or adsorbed onto the surface of the individual particles prior to bonding to form said layer, a finely divided platinum group metal, thereby to form a porous, substrate layer onto which said enzyme is adsorbed or immobilized and comprising a substantially heterogeneous layer of resin-bonded carbon or graphite particles, with said platinum group metal dispersed substantially uniformly throughout said layer.Type: GrantFiled: January 20, 1988Date of Patent: November 13, 1990Assignee: Cambridge Life Sciences plcInventors: Hugh P. Bennetto, Gerard M. Delaney, Jeremy R. Mason, Christopher F. Thurston, John L. Stirling, David R. DeKeyzer
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Patent number: 4968605Abstract: An immobilized enzyme structure in which molecules of one or more enzymes are attached to chemically active groups located on surface in the structure, such structure being composed of melt spun polyamide fibres comprising spaced fibrils of polyamide which are substantially aligned to the axis of the fibre, such aligned spaced fibrils being interconnected to each other in a random manner.Type: GrantFiled: December 22, 1987Date of Patent: November 6, 1990Assignee: Imperial Chemical Industries plcInventor: Nigel W. Hayman
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Patent number: 4963469Abstract: The present invention provides an enzymatically-inactive, immunologically-active .beta.-galactosidase mutein, wherein, in the region between the amino acids 430 and 550, at least one amino acid of the natural sequence is changed to another amino acid and the enzymatic activity does not amount to more than 1%, referred to the native enzyme. The present invention also provides a process for the production of this mutein. Furthermore, the present invention is concerned with the use of this mutein in the immunological determination of serum proteins by the enzyme immunoassay principle.Type: GrantFiled: July 12, 1988Date of Patent: October 16, 1990Assignee: Boehringer Mannheim GmbHInventors: Ralf Mattes, Helmut Lenz, Werner Stock
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Patent number: 4963494Abstract: An enzyme immobilized membrane comprising an anisotropic ultrafiltration membrane having a porous layer and a dense layer, and an enzyme immobilized therein is disclosed. The porous layer of the ultrafiltration membrane retains a water-soluble polymer having at least two functional groups in the crosslinked state, and the enzyme is covalently bonded to the membrane through the functional groups of the polymer. Preferably, the membrane is prepared from polysulfone. The enzyme immobilized membrane is produced by a process which comprises impregnating a solution of the water-soluble polymer into the porous layer of the ultrafiltration membrane under a pressure of 0.1 to 1.0 kg/cm.sup.Type: GrantFiled: March 6, 1989Date of Patent: October 16, 1990Assignee: Nitto Electric Industrial Co., Ltd.Inventors: Ken Hibino, Takeshi Okada, Kazuo Nakao, Yuko Sahashi
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Patent number: 4959306Abstract: Methods and materials for preparing specific binding reagents with a multiplicity of relatively noninterfering label moieties are described. By spacing the labels at the surface of a specific reagent with bulking agent, increased sensitivity can be achieved without interference between individual labeling entities.Type: GrantFiled: November 28, 1986Date of Patent: September 25, 1990Assignee: Sclavo, Inc.Inventors: Naomi Kameda, Gerald L. Rowley
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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: 4952519Abstract: A member of a bioaffinity binding pair is immobilized on a plastic surface by coating the surface with poly(ethyleneimine) derivatized with a hydrophobic group, and covalently coupling the member to the coated surface. The immobilized member may be used in immunoassays or bioaffinity separations. The derivatized poly(ethyleneimine) is preferably tosyl poly(ethyleneimine).Type: GrantFiled: May 2, 1988Date of Patent: August 28, 1990Assignee: E. I. Du Pont de Nemours and CompanyInventor: Phillip H. Lau
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Patent number: 4937188Abstract: Enzyme amplification is achieved by covalently bonding enzyme to a supporting material via a molecular chain which is a substrate for the enzyme, then introducing a small amount of enzyme in the free state to this system, causing release of a large amount of bound enzyme. In an alternative embodiment, complementary enzymatically inactive fragments of an active enzyme, which fragments can recombine to form active enzyme, are covalently attached to separate support materials by a molecular chain material which is a substrate for the active enzyme, and these two fragment-support conjugates are connected in series. Upon application of free enzyme or free complementary enzyme to one of these fragment-support conjugates, followed by application of the resulting product mixture to the second fragment-support conjugate, a large amount of free enzyme is ultimately produced.Type: GrantFiled: April 15, 1986Date of Patent: June 26, 1990Assignee: Northeastern UniversityInventors: Roger W. Giese, Markus Ehrat, Douglas J. Cecchini
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Patent number: 4935465Abstract: A conjugate comprising a pharmaceutically useful protein linked to at least one water-soluble polymer by means of a reversible linking group.Type: GrantFiled: November 27, 1985Date of Patent: June 19, 1990Assignee: Beecham Group p.l.c.Inventor: Andrew J. Garman
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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: 4929556Abstract: Polysulfonium salts that can react with nucleophilic groups and covalently cross-link are used to immobilize enzymes or enzyme-containing cellular material. Some of the polysulfonium salts can both flocculate and covalently cross-link. Replacement of the cross-linker, glutaraldehyde, with the polysulfonium salt results in greater retention of enzyme activity during immobilization. Immobilization is carried out by forming a mixture of an enzyme or enzyme-containing cellular material and the polysulfonium salt and subjecting the mixture to conditions such that sulfonium ions react with nucleophilic groups contained by the enzyme or cellular material to form a covalently cross-linked and water insoluble product. The enzyme or cellular material may be flocculated with a flocculating agent prior to cross-linking with the polysulfonium salt. The polysulfonium salt can be a polymer containing sulfonium groups.Type: GrantFiled: July 8, 1988Date of Patent: May 29, 1990Assignee: The Dow Chemical CompanyInventors: Roberta C. Cheng, Ritchie A. Wessling, Donald L. Schmidt