Attached To The Carrier Via A Bridging Agent Patents (Class 435/181)
  • Patent number: 5418284
    Abstract: A bead composition is disclosed herein which comprises a core of a polyacrylonitrile homopolymer or copolymer and a surface of pendant N-haloamide groups. Also disclosed is a process for the production of said composition.
    Type: Grant
    Filed: September 3, 1993
    Date of Patent: May 23, 1995
    Assignee: Cytec Technology Corp.
    Inventors: Laurence W. Chang, Larry S. Anderson, David A. Ley
  • Patent number: 5416007
    Abstract: Disclosed are methods for increasing the yield of intact target proteins by cleaving fused polypeptides made by recombinant DNA techniques. The fused polypeptides are designed at the DNA level to have a preselected primary cleavage site in a pendant polypeptide fused to a protein of interest. Structural features of the fused polypeptide and cleavage reaction environment are controlled to favor cleavage by a preselected cleavage agent at the primary cleavage site over a second cleavage agent-sensitive amino acid sequence in the target protein. The cleavage reaction is terminated before completion when the ratio of intact target protein to truncated, cleaved target protein is optimized, and the remaining reaction mixture comprising uncleaved fused polypeptide is resubjected to the cleavage agent. The presence of charged organic molecules in the cleavage reaction mixture favors cleavage at the primary cleavage site. The endopeptidase used for cleavage may be immobilized on an insoluble support matrix.
    Type: Grant
    Filed: July 12, 1994
    Date of Patent: May 16, 1995
    Assignee: Creative BioMolecules, Inc.
    Inventors: Marc F. Charette, Roberto Crea, Charles M. Cohen
  • Patent number: 5415938
    Abstract: An improved spacer material for improving the biocompatibility of a biomaterial and a method for making it in which a polyalkylimine is covalently attached to an aminated substrate and combined with a crosslinking agent which is at least difunctional in aldehyde groups. The polyalkylimine can be, for example, polyethyleneimine and the crosslinking agent can be, for example, glutaraldehyde. Preferably, the crosslinking agent is applied in dilute solution and at a pH suitable to accomplish light crosslinking of the polyalkyaimine and also provide aldehyde linkages at the interface between the biomolecule and the spacer.
    Type: Grant
    Filed: February 9, 1994
    Date of Patent: May 16, 1995
    Assignee: Medtronic, Inc.
    Inventors: Patrick T. Cahalan, Michel Verhoeven, Marc Hendriks, Linda Cahalan
  • Patent number: 5412087
    Abstract: Substrates with surfaces comprising compounds with thiol functional groups protected with a photoremovable protecting group can be used to construct arrays of immobilized anti-ligands, such as oligonucleotide probes or other biological polymers. The arrays can be used in assays to detect the presence of complementary nucleic acids in a sample. Spatially addressed irradiation of predefined regions on the surface permits immobilization of oligonucleotides and other biological polymers at the activated regions on the surface. Cycles of irradiation on different regions of the surface and immobilization of different anti-ligands allow formation of an immobilized matrix of anti-ligands at defined sites on the surface. The immobilized matrix of anti-ligands permits simultaneous screenings of a liquid sample for ligands having high affinities for certain anti-ligands of the matrix.
    Type: Grant
    Filed: April 24, 1992
    Date of Patent: May 2, 1995
    Assignee: Affymax Technologies N.V.
    Inventors: Glenn H. McGall, Stephen P. A. Fodor, Edward L. Sheldon
  • Patent number: 5405877
    Abstract: Water-soluble cyclic imide thione activated polyalkylene oxides having improved hydrolytic stability are disclosed. Methods of forming and conjugating the activated polyalkylene oxides with biologically active nucleophiles are also disclosed.
    Type: Grant
    Filed: August 29, 1994
    Date of Patent: April 11, 1995
    Assignee: Enzon, Inc.
    Inventors: Richard B. Greenwald, Anthony J. Martinez
  • Patent number: 5405766
    Abstract: Enzymes and certain other bioactive substances are immobilized on solid substrates which have sufficient functional groups such as hydroxyl or carboxyl. The bioactive substances are linked to the substrates through spacer compounds having a long open alkyl chain with 7-18 carbon atoms and also through phospholipid intermediates. The spacer compound is chemically linked to the substrate. The phospholipid is covalently linked to the spacer compound. Immobilized bioactive substances of the invention exhibit a marked increase in activity and stability. In a preferred embodiment, immobilized enzymes having a high degree of resistance to thermal inactivation are prepared.
    Type: Grant
    Filed: March 25, 1993
    Date of Patent: April 11, 1995
    Assignee: Her Majesty the Queen in right of Canada, as represented by the Minister of National Defence
    Inventors: Krishna M. R. Kallury, Michael Thompson, William E. Lee
  • Patent number: 5403731
    Abstract: A modified superoxide dismutase represented by the formula: ##STR1## (wherein R is as defined below; SOD is a residue of superoxide dismutase) is produced, in a shortened period of reaction with a high and constant modification ratio, by reacting a polymeric carbonyldiimidazole derivative represented by the formula: ##STR2## (wherein R is a residue of a water soluble polymer having an average molecular weight of about 2,000 to 10,000) with superoxide dismutase in the presence of a buffer having a pH of 9.0 to 11.0 and a concentration of 0.1 M to 0.5 M, preferably 0.2 M to 0.4 M, at a temperature of 30.degree. to 70.degree. C., preferably 45.degree. to 60.degree. C. The modified superoxide dismutase thus produced exhibits a suitably prolonged blood half-life.
    Type: Grant
    Filed: December 3, 1993
    Date of Patent: April 4, 1995
    Assignee: JCR Pharmaceuticals Co., Ltd.
    Inventors: Yoshiyuki Nakano, Hajime Hiratani, Kazuo Kato
  • Patent number: 5403706
    Abstract: A carrier matrix of polyvinyl alcohol-coated glass is dissolvably impregnated with reagent. The matrix is manufactured by slurrying glass fibers in an excess of water and polyvinyl alcohol and forming a layer, which is then dried and impregnated with reagent.
    Type: Grant
    Filed: July 20, 1989
    Date of Patent: April 4, 1995
    Assignee: Boehringer Mannheim GmbH
    Inventors: Hans-Erich Wilk, Dieter Mangold, Rolf Lerch, Joachim Steinbiss
  • Patent number: 5403750
    Abstract: Affinity matrices useful for the chromatography and immobilization of biological materials and the method of preparing and using the same are disclosed. The affinity supports are based on hydrated polyurethane polymers which have been activated to provide a means for covalently attaching a variety of bioaffinity agents. The hydrated polymer matrices are characterized by their biocompatibility and resistance to nonspecific protein adsorption. Preferably, the prepolymers used to prepare the hydrated polymers are isocyanate-capped oxyethylene-based diols or polyols, at least 75% of said diols and polyols having a molecular weight of 7000 to about 30,000.
    Type: Grant
    Filed: April 8, 1991
    Date of Patent: April 4, 1995
    Assignee: W. R. Grace & Co.-Conn.
    Inventors: James A. Braatz, Aaron H. Heifetz
  • Patent number: 5401647
    Abstract: Disclosed is a method of preparing limulus amoebocyte lysate substantially free from factor G which comprises bringing limulus amoebocyte lysate into contact with an insoluble carrier on which a (1.fwdarw.3)-.beta.-D-glucoside structural portion represented by the following formula [I] produced by depolymerizing and/or fractionating a carbohydrate chain is immobilized: ##STR1## wherein n represents an integer of 2 to 370.
    Type: Grant
    Filed: May 27, 1992
    Date of Patent: March 28, 1995
    Assignee: Seikagaku Kogyo Kabushiki Kaisha (Seikagaku Corporation)
    Inventors: Shigenori Tanaka, Jun Aketagawa, Yuko Shibata
  • Patent number: 5399501
    Abstract: A specific binding member such as an antigen or antibody is immobilized by covalent attachment to a solid phase such as a latex microparticle. The solid phase is reacted with a heterobifunctional or homobifunctional coupling agent to form a complex that is then reacted with a dithiol compound to form a thiolated solid phase. A specific binding member is reacted with the coupling agent to form a complex which is then reacted with the thiolated solid phase to link the specific binding member to the solid phase through thioethers. Alternatively, the dithiol compound may be reacted with the specific binding member/coupling agent complex to form a thiolated complex that is reacted with the solid phase/coupling agent complex. The coupling agent may contain a spacer. In another embodiment, the solid phase is reacted with a disulfide compound to form a complex and the complex is reacted with a reductant to form a thiolated solid phase which is reacted with a specific binding member/coupling agent complex.
    Type: Grant
    Filed: March 16, 1992
    Date of Patent: March 21, 1995
    Assignee: Abbott Laboratories
    Inventors: Mark R. Pope, Kevin M. Knigge
  • Patent number: 5399665
    Abstract: Polymers more suitable for use in organ transplantation are formed by coupling biologically active moieties to the free amino groups of polymers formed by incorporation of .alpha. amino acids into polymers formed of alpha hydroxy acids such as lactic acids. In the preferred embodiment, the peptides are coupled to the free amino groups.
    Type: Grant
    Filed: November 5, 1992
    Date of Patent: March 21, 1995
    Assignees: Massachusetts Institute of Technology, Children's Hospital
    Inventors: Denise Barrera, Robert S. Langer, Peter T. Lansbury, Jr., Joseph P. Vacanti
  • Patent number: 5397695
    Abstract: 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, such as enzymes, polypeptides and proteins. This attachment is carried out using carbamoylonium compounds which react with the carboxyl groups 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 carbamoylonium compound.
    Type: Grant
    Filed: June 29, 1989
    Date of Patent: March 14, 1995
    Assignee: Eastman Kodak Company
    Inventors: Richard C. Sutton, Susan J. Danielson, Pranab Bagchi, Patricia M. Scensny
  • Patent number: 5391463
    Abstract: Irradiating, with ultraviolet light, surfaces which contain thiol groups, epoxy groups, or vicinal diol groups, results in surfaces which exhibit a reduced adsorption of biomolecules. In the case of surfaces having thiol groups such irradiation also results in a reduced capacity for the bonding of heterobifunctional crosslinking reagents. Such irradiation may be carried out in a patternwise fashion to obtain patterned surfaces.
    Type: Grant
    Filed: April 25, 1991
    Date of Patent: February 21, 1995
    Assignees: The United States of America as represented by the Secretary of the Navy, Geo-Centers, Inc.
    Inventors: Frances S. Ligler, Suresh Bhatia, Lisa C. Shriver-Lake, Jacque Georger, Jeff Calvert, Charles Dulcey
  • Patent number: 5389533
    Abstract: Biochemical substances such as enzymes are immobilized by reaction with epoxy groups of an olefinic-unsaturated, epoxyfunctional polyether. Prior to immobilization, the polyether is applied to a carrier and crosslinked by treatment with high-energy radiation or peroxide to form a layer. After reacting the biochemical substance with epoxy groups, non-reacted epoxy groups are reacted with a compound containing an amino group and/or a carboxyl group such as an amino acid. Before immobilizing of the biochemical substance and after crosslinking, the polyether may be hydrophilized by reacting some of the epoxy groups with a hydrophilic compound such as an amino acid.
    Type: Grant
    Filed: March 22, 1993
    Date of Patent: February 14, 1995
    Assignee: Siemens Aktiengesellschaft
    Inventors: Wolfgang von Gentzkow, Hans-Dieter Feucht
  • Patent number: 5389534
    Abstract: A biosensor is prepared having a selective detection system containing a biochemical substance such as an enzyme immobilized by reaction with epoxy groups of an olefinic-unsaturated, epoxyfunctional polyether. Prior to immobilization, the polyether is applied to a carrier and crosslinked by treatment with high-energy radiation or peroxide to form a layer. After reacting the biochemical substance with epoxy groups, non-reacted epoxy groups are reacted with a compound containing an amino group and/or a carboxyl group such as an amino acid. Before immobilizing of the biochemical substance and after crosslinking, the polyether may be hydrophilized by reacting some of the epoxy groups with a hydrophilic compound such as an amino acid.
    Type: Grant
    Filed: March 22, 1993
    Date of Patent: February 14, 1995
    Assignee: Siemens Aktiengesellschaft
    Inventors: Wolfgang von Gentzkow, Hans-Dieter Feucht
  • Patent number: 5384254
    Abstract: Poly(fluoroalkyl) sugar reagents are prepared containing a sugar such as a monosaccharide or a disaccharide to which are bonded a plurality of fluoroalkyl anchor groups capable of attaching to a fluorocarbon surface, and either a reactive group capable of covalent coupling to a biomolecule such as an enzyme or a charged group to form an ion-exchanger or a non-ionic group to give a neutral fluorosurfactant. A spacer may be between the reactive group and the sugar. The poly(fluoroalkyl) sugar reagents are strongly adsorbed onto fluorocarbon surfaces to provide supports for such applications as separation and immobilization of biomolecules such as enzymes, carrying out heterogeneous diagnostic assays, and preparation of biosensors.
    Type: Grant
    Filed: May 20, 1993
    Date of Patent: January 24, 1995
    Assignee: E. I. Du Pont de Nemours and Company
    Inventors: Rene Arentzen, Prabhakar K. Jadhav, Robert K. Kobos, Bruce E. Smart
  • Patent number: 5380658
    Abstract: A phosphazene polymer carrier is prepared that has functional groups capable of binding a biologically active substance such as an enzyme or antibody and groups which are non-reactive and hydrophilic. A bifunctional aldehyde is reacted with primary amino groups of a shaped phosphazene polymer to form side chains having aldehyde groups, an amino group-containing compound is reacted with a portion of the aldehyde groups to produce the groups that are non-reactive and hydrophilic, and aldehyde groups not reacted are capable of binding a biologically active substance. The phosphazene polymer may be crosslinked prior to reacting with the bifunctional aldehyde.
    Type: Grant
    Filed: September 16, 1993
    Date of Patent: January 10, 1995
    Assignee: Teijin Limited
    Inventors: Toshitsugu Matsuki, Noritsugu Saiki, Shingo Emi
  • Patent number: 5369012
    Abstract: A portion of an organic polymer article such as a membrane is made hydrophilic by exposing a hydrophobic surface of the article to a depth of about 50 to about 5000 angstroms to atomic oxygen or hydroxyl radicals at a temperature below 100.degree. C., preferably below 40.degree. C., to form a hydrophilic uniform surface layer of hydrophilic hydroxyl groups. The atomic oxygen and hydroxyl radicals are generated by a flowing afterglow microwave discharge, and the surface is outside of a plasma produced by the discharge. A membrane having both hydrophilic and hydrophobic surfaces can be used in an immunoassay by adhering antibodies to the hydrophobic surface. In another embodiment, the membrane is used in cell culturing where cells adhere to the hydrophilic surface. Prior to adhering cells, the hydrophilic surface may be grafted with a compatibilizing compound.
    Type: Grant
    Filed: March 26, 1992
    Date of Patent: November 29, 1994
    Assignee: The United States of America as represented by the Administrator of the National Aeronautics and Space Administration
    Inventors: Steven L. Koontz, Glenn F. Spaulding
  • Patent number: 5352574
    Abstract: New variants of electroactive and optoactive polymers are formed from the surface chemical modification and derivization of free-standing and substrate-supported polymer films. The free-standing or substrate-supported films are chemically modified at or near their surfaces to introduce hydrophilic and/or reactive functional groups, such as carboxylic acids, hydroxyls, and amines. Surface derivatization of the modified polymer film is achieved through the specific attachment of bioactive, immunoactive, electroactive, and catalytic agents to the surface of the electroactive or optoactive polymer film. In one embodiment, a polymer selected from polyacetylene, polypyrrole, polyanilane and polythiophene is modified to contain functional groups and an indicator reagent is covalently coupled to the functional groups. When an analyte in a sample reacts with the indicator reagent, electrical conductivity of the polymer is changed and presence of the analyte is indicated by the change in electrical conductivity.
    Type: Grant
    Filed: October 4, 1991
    Date of Patent: October 4, 1994
    Inventor: Anthony Guiseppi-Elie
  • Patent number: 5348873
    Abstract: An anti-thrombogenic substance is immobilized on a base of a medical device to impart anti-thrombogenic properties to the medical device. The method comprises the steps of applying a photo-reactive azide derivative macromolecular material to a base to form a bonding layer, coating the bonding layer with a macromolecular layer composed of a water-soluble photo-crosslinking macromolecular material containing the anti-thrombogenic substance, and irradiating the base with ultraviolet light with the bonding layer and the macromolecular layer formed thereon to develop inter-molecular covalent bonding in the bonding layer. The macromolecular layer containing the anti-thrombogenic substance is thus fixed onto the base. Concurrently, the anti-thrombogenic substance is immobilized in the macromolecular layer which is crosslinked. The azide derivative can be poly-m-azidostyrene, copolymers, of poly-m-aziodstyrene with styrene and copolymers of poly-m-azidostyrene with methyl methacrylate.
    Type: Grant
    Filed: October 19, 1992
    Date of Patent: September 20, 1994
    Assignee: K.K. Vayu
    Inventors: Takehisa Matsuda, Yasuhide Nakayama, Takashi Sugawara
  • Patent number: 5342772
    Abstract: 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: Grant
    Filed: February 10, 1993
    Date of Patent: August 30, 1994
    Assignees: E. I. du Pont de Nemours and Company, Baylor University
    Inventors: Rene Arenzen, Patrick Boivin, Robert K. Kobos, William H. Scouten, Bruce E. Smart
  • Patent number: 5342770
    Abstract: 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: Grant
    Filed: May 11, 1993
    Date of Patent: August 30, 1994
    Assignee: Chisso Corporation
    Inventor: Nobuyuki Yamasaki
  • Patent number: 5328840
    Abstract: The present invention provides new compounds and methods for promoting platelet aggregation, and controlling bleeding. The present invention is based on the surprising discovery that erythrocytes conjugated to certain peptides and polypeptides containing an R-G-D (Arg-Gly-Asp) sequence (collectively termed herein "RGD peptides") according to the invention, selectively bind to activated platelets but not to unactivated platelets. In recognition of the dual nature of the derivatized erythrocytes, they are termed herein "thrombo-erythrocytes". The thrombo-erythrocytes have no significant change in their rheological properties. In a preferred aspect, the thrombo-erythrocytes have the majority of RGD peptide cross-linked specifically to glycophorin A and glycophorin B on the surface of the erythrocyte.
    Type: Grant
    Filed: November 12, 1991
    Date of Patent: July 12, 1994
    Assignee: The Research Foundation of the State University of New York
    Inventor: Barry S. Coller
  • Patent number: 5314810
    Abstract: A fructose transferring enzyme is immobilized by adsorption on a granular carrier having a primary to quaternary amine. The carrier is preferably an epoxy polymer, a vinyl polymer or a chitosan derivative having a primary, secondary or tertiary amine. Immobilization can be performed without or with a crosslinking agent. The immobilized enzyme is used for producing fructooligosaccharides by passing a sucrose solution through a column containing the immobilized enzyme.
    Type: Grant
    Filed: May 19, 1992
    Date of Patent: May 24, 1994
    Assignee: Meiji Seika Kaisha, Ltd.
    Inventors: Toshiaki Kono, Goichi Yamaguchi, Hidemasa Hidaka
  • Patent number: 5312744
    Abstract: A method is provided for immobilizing and preserving an immunologically reactive antigen substance such as antigenic cells or non-cell bound antigens for use in solid-phase immunoassay. The antigen substance is adsorbed and crosslinked on a support and contacted with a protecting solution and containing sugar and an antiseptic substance such as NaN.sub.3. The antigen substance is preferably centrifugally contacted with the support to shorten the time for adsorption. Crosslinking is with a solution of 1.0 to 5.0% formaldehyde or 0.003 to 0.06% glutaraldehyde. The antigenic cells can be a blood component such as platelets.
    Type: Grant
    Filed: June 9, 1992
    Date of Patent: May 17, 1994
    Assignee: Olympus Optical Co., Ltd.
    Inventor: Yoichi Shibata
  • Patent number: 5308641
    Abstract: An improved spacer material for improving the biocompatibility of a biomaterial and a method for making it in which a polyalkylimine is covalently attached to an aminated substrate and combined with a crosslinking agent which is at least difunctional in aldehyde groups. The polyalkylizine can be, for example, polyethyleneimine and the crosslinking agent can be, for example, glutaraldehyde. Preferably, the crosslinking agent is applied in dilute solution and at a pH suitable to accomplish light crosslinking of the polyalkylimine and also provide aldehyde linkages at the interface between the biomolecule and the spacer.
    Type: Grant
    Filed: January 19, 1993
    Date of Patent: May 3, 1994
    Assignee: Medtronic, Inc.
    Inventors: Patrick T. Cahalan, Michel Verhoeven, Marc Hendriks, Linda Cahalan
  • Patent number: 5306632
    Abstract: A porous shaped substrate such as a porous bead is formed from polyacrylonitrile or a copolymer thereof containing nitrile groups. The substrate has a hydrophilic surface containing amide groups constituting about 1.8 mole percent to less than about 15 mole percent of the total nitrile groups, and containing no amide or carboxyl groups. The substrate is substantially non-swellable in water and is able to resist pressures in a columnar bed of up to about 3000 psi without collapsing. In forming the amide groups, polyacrylonitrile or copolymer thereof containing nitrile groups, an alkaline catalyst such as sodium hydroxide and a nonsolvent for the substrate such as methanol are combined to form a suspension. A peroxide is added to the suspension and the suspension is heated to hydrolyze nitrile groups to amide groups. Succinylated aminoethyl groups or activated carboxyl groups can be formed on the substrate and a bioactive ligand such as p-aminobenzamidine covalently bonded to the substrate.
    Type: Grant
    Filed: February 25, 1993
    Date of Patent: April 26, 1994
    Assignee: Cytec Technology Corp.
    Inventors: Larry S. Anderson, Michael T. Cooke, David A. Ley
  • Patent number: 5298430
    Abstract: Immunoassay process for the detection of an antigen in a sample of blood, serum, urine and other liquids employing a test apparatus comprising a reaction chamber and a support element in the reaction chamber comprising a blend of from about 5 to 95 percent cellulose organic ester fibrets and from about 95 to 5 percent by weight of a dispersible cut fibers where a predetermined amount of an antibody capable of extracting an antigen from the sample is bound to the support element, the process comprising depositing the sample on the upper surface of the support element and detecting the amount of antigen in the sample.
    Type: Grant
    Filed: September 13, 1988
    Date of Patent: March 29, 1994
    Assignee: Hoechst Celanese Corporation
    Inventors: Thomas J. Myers, Jr., Lessie C. Phillips
  • Patent number: 5294551
    Abstract: A composition which can bind heparin and promote cellular adhesion and neurite outgrowth is provided which consists essentially of a polypeptide of the formula:tyr-glu-lys-pro-gly-ser-pro-pro-arg-glu-val-val-pro-arg-pro-arg-pro-gly-vallys-asn-asn-gln-lys-ser-glu-pro-leu-ile-gly-arg-lys-lys-thr-asp-glu-leu,lys-asn-asn-gln-lys-ser-glu-pro-leu-ile-gly-arg-lys-lys-thr,leu-ile-gly-arg-lys-lys-thr,tyr-arg-val-arg-val-thr-pro-lys-glu-lys-thr-gly-pro-met-lys-glu,ser-pro-pro-arg-arg-ala-arg-val-thr,trp-gln-pro-pro-arg-ala-arg-ile,or mixtures thereof. Medical devices such as prosthetic implants, percutaneous devices and cell culture substrates coated with the polypeptide composition are also provided. Cell culture substrates provided can be made of a synthetic resin and in the form of a bead, microporous fiber or well of a microtiter plate.
    Type: Grant
    Filed: September 9, 1992
    Date of Patent: March 15, 1994
    Assignee: Regents of the University of Minnesota
    Inventors: Leo T. Furcht, James B. McCarthy
  • Patent number: 5292649
    Abstract: The reaction of a lipase upon a fatty acid is effected by an improved method which comprises bringing the lipase bonded at multiple points to an anion-exchange residue or a carrier and a carrier having a free anion-exchange group admixed therewith into contact with a reaction mixture containing an oily substance including the fatty acid and a water-soluble substance thereby forming an oily product and a water-soluble product in the reaction mixture and subsequently separating the two reaction products.
    Type: Grant
    Filed: July 9, 1992
    Date of Patent: March 8, 1994
    Assignee: Agency of Industrial Science & Technology, Ministy of International Trade & Industry
    Inventors: Yoshitsugu Kosugi, Hideo Suzuki, Akio Sato
  • Patent number: 5286637
    Abstract: New biologically active drug polymer derivatives, namely peptides or protein derivatives, are useful medicaments and are represented by the generic formula:RO--(CH.sub.2 --CH.sub.2 O).sub.n --(CO)--NH--X--(CO)--NH--Z (I)whereinR represents a lower alkyl group,n is an integer comprised between 25 and 250,X when combined with adjacent NH and CO groups represents an amino acid or a dipeptide or tripeptide residue, andZ when combined with the adjacent NH group represents a biologically active peptide or protein or NH or NH.sub.2 containing drug residue.
    Type: Grant
    Filed: January 7, 1993
    Date of Patent: February 15, 1994
    Assignee: Debiopharm, S.A.
    Inventors: Francesco Veronese, Luciana Sartore, Piero Orsolini, Romano Deghenghi
  • Patent number: 5284911
    Abstract: A composition is disclosed herein which comprises a core of a polyacrylonitrile homopolymer or copolymer and a surface of N-haloamides. Also disclosed is a process for the production of said composition.
    Type: Grant
    Filed: November 18, 1992
    Date of Patent: February 8, 1994
    Assignee: American Cyanamid Company
    Inventors: Laurence W. Chang, Larry S. Anderson, David A. Ley
  • Patent number: 5284910
    Abstract: A surface-modified fibrillated fiber composition is disclosed herein which comprises polyacrylonitrile homopolymer or copolymer and a surface of pendant N-haloamide groups. Also disclosed is a process for the production of said composition.
    Type: Grant
    Filed: July 9, 1992
    Date of Patent: February 8, 1994
    Assignee: American Cyanamid Company
    Inventors: Laurence W. Chang, Larry S. Anderson, David A. Ley
  • Patent number: 5283034
    Abstract: A method and composition which permits sterilization of surfaces coupled with biologically active moieties by ionizing radiation is described. The protecting composition contains a surface-stabilizing agent which adheres to the surface and has a molecular weight.gtoreq.5 kd, and an oxygen radical scavenger which is preferably a di- or polysaccharide or reduced form thereof. In the method of the invention, a surface which is coupled to a biologically active agent is protected with the invention composition, dried to a moisture content of less than 1%, and then sterilized by ionizing radiation under standard conditions. The sterilized surfaces of the invention are particularly useful in the production of medical devices intended for extracorporeal use, particularly in cell-separation techniques.
    Type: Grant
    Filed: March 26, 1992
    Date of Patent: February 1, 1994
    Assignee: Applied Immune Sciences, Inc.
    Inventors: David A. Okrongly, Donald Lamons, Thomas B. Okarma
  • Patent number: 5279954
    Abstract: 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: Grant
    Filed: June 30, 1989
    Date of Patent: January 18, 1994
    Assignee: Board of Regents of the University of Nebraska and BioNebraska
    Inventors: Fred W. Wagner, Thomas R. Coolidge, Dwane E. Wylie, Sheldon M. Schuster, William Lewis, Jay Stout
  • Patent number: 5279955
    Abstract: 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: Grant
    Filed: March 1, 1991
    Date of Patent: January 18, 1994
    Inventors: Randall K. Pegg, Mary S. Saunders
  • Patent number: 5272087
    Abstract: An enzymatic electrode, having a homogeneous composition throughout, consists essentially of a uniform intimate admixture of a conducting powder with at least one immobilized enzyme, or with an immobilized enzyme and a mediator agent or a co-enzyme, in a matrix. The electrode is one which has a surface available for direct contact with a substrate without a permeable or semi-permeable intermediate membrane or membranes. The enzymatic electrode is prepared, e.g., by intimately admixing (a) a homogeneous paste or matrix (resulting from an intimate admixture of a conducting powder with a binder), (b) at least one enzyme and (c) an enzyme crosslinking solution, and then incorporating therein a mediator agent and/or a co-enzyme.
    Type: Grant
    Filed: October 16, 1990
    Date of Patent: December 21, 1993
    Assignee: Centre National de la Recherche Scientifique (C.N.R.S.)
    Inventors: Nabil El Murr, Mohamed Slilam
  • Patent number: 5270193
    Abstract: 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: Grant
    Filed: October 24, 1991
    Date of Patent: December 14, 1993
    Assignee: E. I. DuPont de Nemours and Company
    Inventor: John W. D. Eveleigh
  • Patent number: 5268287
    Abstract: 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: Grant
    Filed: October 26, 1990
    Date of Patent: December 7, 1993
    Assignee: Teijin Limited
    Inventors: Toshitsugu Matsuki, Noritsugu Saiki, Shingo Emi
  • Patent number: 5268306
    Abstract: 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: Grant
    Filed: December 23, 1991
    Date of Patent: December 7, 1993
    Assignee: Boehringer Mannheim GmbH
    Inventors: Michael Berger, Arno Deger, Josef Maier
  • Patent number: 5266471
    Abstract: 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: Grant
    Filed: February 25, 1991
    Date of Patent: November 30, 1993
    Assignee: ROHM
    Inventor: Stefan Schmitt
  • Patent number: 5258041
    Abstract: A method for attaching a biomolecule to a support having a hydrophobic surface, involving the use of a long chain chemical spacer having a hydrophobic guiding group capable of becoming embedded in the surface, and the biomolecule being covalently bound to the spacer at its opposite end.
    Type: Grant
    Filed: March 19, 1991
    Date of Patent: November 2, 1993
    Assignee: Bio-Metric Systems, Inc.
    Inventors: Patrick Guire, Shawn G. Dunkirk
  • Patent number: 5246846
    Abstract: 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: Grant
    Filed: December 31, 1990
    Date of Patent: September 21, 1993
    Inventors: Fritz Pittner, Thomas Schalkhammer, Gerald Urban, Eva Mann-Buxbaum
  • Patent number: 5242826
    Abstract: A polypeptide which can bind heparin and promote cellular adhesion is provided, which consists essentially of a polypeptide having a formula selected from the group consisting of:met-phe-lys-lys-pro-thr-pro-ser-thr-leu-lys-ala-gly-glu-leu-arg,thr-ala-gly-ser-cys-leu-arg-lys-phe-ser-thr met,asn-pro-leu-cys-pro-pro-gly-thr-lys-ile-leu,and mixtures thereof.Medical devices such as prosthetic implants, percutaneous devices, bandages and cell culture substrates coated with the polypeptide composition are also provided.
    Type: Grant
    Filed: May 24, 1991
    Date of Patent: September 7, 1993
    Assignee: Regents of the University of Minnesota
    Inventors: Effie C. Tsilibary, Leo T. Furcht
  • Patent number: 5243037
    Abstract: Poly(fluoroalkyl) sugar reagents are prepared containing a sugar such as a monosaccharide or a disaccharide to which are bonded multiple fluoroalkyl anchor groups capable of attaching to a fluorocarbon surface, and either a reactive group capable of covalent coupling to a biomolecule or a charged group to form an ion-exchanger or a non-ionic group to give a neutral fluorosurfactant. A spacer may be between the reactive group and the sugar. The poly(fluoroalkyl) sugar reagents are strongly adsorbed onto fluorocarbon surfaces to provide supports for such applications as separation and immobilization of biomolecules such as enzymes, carrying out heterogeneous diagnostic assays, and preparation of biosensors.
    Type: Grant
    Filed: September 21, 1990
    Date of Patent: September 7, 1993
    Assignee: E. I. Du Pont de Nemours and Company
    Inventors: Rene Arentzen, Prabhakar K. Jadhav, Robert K. Kobos, Bruce E. Smart
  • Patent number: 5240747
    Abstract: A process for modifying the surface of a material such as plastics, metals, glasses and ceramics which comprises the steps of (1) coating a compound having at least one azido group on the surface of the material to be modified, (2) making a modifier substance to be fixed for the modification exist on or in the coated surface, and (3) irradiating ultraviolet rays to the coated surface to fix the modifier substance to the coated surface, wherein various compounds can be used as the modifier for converting the characteristics of the material surface to the desired characteristics without previously treating them, and various materials can be easily modified with a firm fixing of the modifier.
    Type: Grant
    Filed: August 2, 1991
    Date of Patent: August 31, 1993
    Assignee: Kanegafuchi Kagaku Kogyo Kabushiki Kaisha
    Inventors: Takehisa Matsuda, Takashi Sugawara, Kazuhiko Inoue, Nobutaka Tani
  • Patent number: 5241012
    Abstract: Solid substrates and methods for their preparation are provided, where enhanced functionalization of solid substrates is achieved, so that higher levels of binding of a wide variety of moieties can be obtained. The surface is nitrated with a nitronium agent, where the nitro groups may be modified in a variety of ways to serve as sites for linking. The resulting solid substrates find use in therapy, diagnosis and processing.
    Type: Grant
    Filed: May 19, 1987
    Date of Patent: August 31, 1993
    Assignee: Applied Immune Sciences, Inc.
    Inventor: Brian Clark
  • Patent number: 5234991
    Abstract: A porous mineral support such as a porous mineral oxide coated with an aminated polysaccharide polymer has cationic characteristics and is capable of reversibly fixing thereto biological macromolecules. This material is employed in the separation and purification of said biologic macromolecules.
    Type: Grant
    Filed: March 17, 1987
    Date of Patent: August 10, 1993
    Assignee: Pasteur Merieux Serums and Vaccines
    Inventors: Jean-Louis Tayot, Michel Tardy
  • Patent number: 5234820
    Abstract: 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: Grant
    Filed: June 28, 1990
    Date of Patent: August 10, 1993
    Assignees: 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