Peptides Or Proteins Is Immobilized On, Or In, An Inorganic Carrier Patents (Class 530/811)
  • Patent number: 5925552
    Abstract: Methods are provided for forming a coating of an immobilized biomolecule on a surface of a medical device to impart improved biocompatibility for contacting tissue and bodily fluids. A biomolecule such as a glycoprotein having an unsubstituted amide moiety is combined with an amine forming agent to form an amine-functional biomolecule. The amine-functional biomolecule is combined with a medical device surface having a chemical moiety such as aldehyde, epoxide, isocyanate, 1,2-dicarbonyl, phosphate, sulphate or carboxylate to form a chemical bond immobilizing the biomolecule on the surface. The chemical bond may be combined with a reducing agent or a stabilizing agent. The aldehyde moiety may be formed by combining a periodate with a 2-aminoalcohol moiety or a 1,2-dihydroxy moiety. Alternatively, an amine-functional medical device surface is combined with a biomolecule having a chemical moiety that reacts with an amine moiety.
    Type: Grant
    Filed: April 27, 1998
    Date of Patent: July 20, 1999
    Assignee: Medtronic, Inc.
    Inventors: James R. Keogh, Paul V. Trescony
  • Patent number: 5910405
    Abstract: The present invention relates to the epitopes of hepatitis C virus (HCV) core protein and non-structural 3 protein (NS3), and the epitopes of envelope protein, epitopes of non-structural 4 protein, and the epitopes of HCV non-structural 5 protein and a recombinant protein comprising the same; processes for producing the recombinant proteins; an agent for diagnosing antibodies against hepatitis C virus in a putative serum sample, which comprises said recombinant proteins; and a process for diagnosing hepatitis C by using the agent.
    Type: Grant
    Filed: October 24, 1995
    Date of Patent: June 8, 1999
    Assignee: Lucky Limited
    Inventors: Joong Myung Cho, Deog Young Choi, Chun Hyung Kim, Hong Seob So, Jae Young Yang, In Soo Kim, Joo Ho Kim
  • Patent number: 5891341
    Abstract: The present invention is directed to compositions and devices based upon the unexpected discovery that certain antibacterial proteins, in particular lysozyme and lactoferrin, bind to advanced glycosylation endproducts (AGEs) with high affinity, and that this binding activity is substantially noncompetitive with binding of bacterial carbohydrates to the antibacterial proteins. Accordingly, the invention relates to methods for treating diseases and disorders associated with increased levels of AGEs, by using compositions and devices having associated therewith a molecule having a hydrophilic loop domain, which domain is associated with AGE-binding activity, and compositions comprising such a domain. The invention further relates to compositions and devices for partitioning AGEs away from a sample.
    Type: Grant
    Filed: April 5, 1996
    Date of Patent: April 6, 1999
    Assignee: The Picower Institute for Medical Research
    Inventors: Yong Ming Li, Helen Vlassara, Anthony Cerami
  • Patent number: 5872013
    Abstract: An aggregate for qualitatively or quantitatively determining bindable substances. Said aggregate comprises an ultra small colloidal particle and a specific binding agent characterized in that the mean diameter of the colloidal particle is below 2 nm. Preferably the size of the metal particle is selected so that the aggregate is capable of penetrating in standard biological specimens. The invention further provides a universally applicable detection system for determining bindable substances in particular in living material. Further there is provided a process for preparing said aggregate.
    Type: Grant
    Filed: October 4, 1995
    Date of Patent: February 16, 1999
    Assignee: Janssen Pharmaceutica N.V.
    Inventors: Johannes Leonardus Maria Leunissen, Marc Joris De Brabander, Petrus Franciscus Elisabeth Maria Van de Plas
  • Patent number: 5872207
    Abstract: Peptides or peptides having an amino acid-like moiety in place of an amino acid moiety thereof immobilized on glass beads, especially controlled-pore glass beads, by a C-terminal .alpha.-carboxyl-.omega.-amino linker and .alpha.-silyl-.omega.-amino anchor, especially wherein the anchor has the structural formula--NH(CH.sub.2).sub.n Si(OR).sub.2 O--wherein n is 3 and R is hydrogen or the glass bead and the linker has the structural formula--?NH(CH.sub.2).sub.r CO!.sub.
    Type: Grant
    Filed: August 29, 1995
    Date of Patent: February 16, 1999
    Assignee: Sanofi Pharmaceuticals, Inc.
    Inventors: Barry Arnold Morgan, Mark Alan Ator, James Arthur Gainor, Thomas Douglas Gordon, Lawrence Ivan Kruse, Teruna Jaya Siahaan
  • Patent number: 5871747
    Abstract: The invention concerns the use, in the induction of an immune response, of a synthetic microparticle polymer carrying on the surface one or more covalently bonded proteins capable of carrying one or more epitopes, the densities of the protein(s) on the surface of the microparticles, and their molecular weights, being adjusted so as to direct the immune response to the induction of a humoral and cellular response or to the induction of a largely cellular response. Said microparticles have an average diameter of approximately 0.25 to 1.5 .mu.m.
    Type: Grant
    Filed: April 28, 1995
    Date of Patent: February 16, 1999
    Assignee: Institut Pasteur
    Inventors: Christine Gengoux-Sedlik, Claude LeClerc
  • Patent number: 5861319
    Abstract: Methods and compositions are provided for specific binding assays in which specific binding reagents are immobilized on a solid phase. Immobilization is facilitated by covalently coupling specific binding assay reagents such as polypeptide receptors or analytes with water soluble polymers. Such water soluble polymers, for example star polymers such as dendrimers, provide production advantages of lot-to-lot uniformity and homogeneity, and can enhance sensitivity due to low non-specific binding to the solid phase.
    Type: Grant
    Filed: October 28, 1994
    Date of Patent: January 19, 1999
    Assignee: Dade Behring Inc.
    Inventors: Spencer H. Lin, Kwok Sum Yu, Pratap Singh, Steven E. Diamond
  • Patent number: 5843405
    Abstract: The invention relates to peptides or fragments thereof which are immunochemically reactive with Epstein-Barr Virus (EBV) antibodies. New antibodies directed to said peptides or fragments thereof are also part of the invention.The invention also relates to a method for the detection of EBV or antibodies directed against EBV in a test fluid and also to an immunochemical reagent comprising a peptide, a fragment or a polypeptide according to the invention and a test kit to be used when applying the said detection methods.Detection of EBV in a test fluid or tissue specimen using antibodies, monoclonal and polyclonal, directed to the said peptide, which have the characteristics of detecting both native and denatured EBV-EA protein is also part of said invention.
    Type: Grant
    Filed: June 6, 1996
    Date of Patent: December 1, 1998
    Assignee: Akzo Nobel N.V.
    Inventor: Jaap Michiel Middeldorp
  • Patent number: 5840862
    Abstract: Macromolecules such as nucleic acid strands are aligned, adhered and stretched on a support surface by passing the strands through a meniscus of a solvent containing the strands. The meniscus may be that of a solvent between two surfaces at an interface of the solvent with air. One end of a nucleic acid strand is attached to one surface which may be a glass surface and another end is free. The meniscus is moved relative to the surface to which the end is attached such as by evaporating the solvent or by moving the surface. As the nucleic acid strand passes through the meniscus, the strand elongates and aligns perpendicular to the meniscus on the surface. This method may be used in assaying, measuring intramolecular distance of and/or separating macromolecules.
    Type: Grant
    Filed: June 6, 1995
    Date of Patent: November 24, 1998
    Assignees: Institut Pasteur, Centre National de la Recherche Scientifique, both of
    Inventors: David Bensimon, Aaron Bensimon, Fran.cedilla.ois Heslot
  • Patent number: 5837826
    Abstract: Porous zirconia particles of specific gravity of 2.5-3.5 g/cm.sup.3 and mean particle sizes of 30-400 .mu.m can be synthesized using oil emulsion methods from colloids and used for protein adsorption in stable expanded beds. Expanded beds of less than 1.0 settled bed height to diameter (approximately 10 ml bed volume) are stable at linear fluid velocities of at least about 100 cm/hour.
    Type: Grant
    Filed: February 27, 1995
    Date of Patent: November 17, 1998
    Assignee: Regents of The University of Minnesota
    Inventors: Michael C. Flickinger, Michael J. Robichaud, John E. Morris, Colleen M. Griffith, Michael J. Annen, Peter W. Carr, Christopher Dunlap
  • Patent number: 5837808
    Abstract: A tyrosine-substituted hirudin analog has antithrombogenic activity. Further simultaneous reaction at native tyrosine residues is prevented by mutation at those sites to encode nonreactive amino acids. Several novel strategies for coupling the hirudin analog to solid surfaces while simultaneously conserving antithrombogenic activity are disclosed.
    Type: Grant
    Filed: June 19, 1995
    Date of Patent: November 17, 1998
    Assignee: Baxter International Inc.
    Inventors: Cecilia S. L. Ku, Richard Johnson, Julian P. Breillatt, Jr.
  • Patent number: 5824526
    Abstract: A sol-gel glass doped with one or more reagent that provides chemical interactions with diffusible solutes or components in an adjacent liquid or gas phase. The reagent(s), the solutes or the components can be any organic or inorganic compounds or materials of biological origin, including enzymes. The doped sol-gel glass in various forms is useful as an analytical test, chromatographic medium, sensor, catalyst or biocatalyst, electrode or enzyme electrode, and other detection devices.
    Type: Grant
    Filed: June 21, 1996
    Date of Patent: October 20, 1998
    Assignee: YISSUM, Research Development Company of the Hebrew University of Jerusalem, Israel
    Inventors: David Avnir, Michael Ottolenghi, Sergei Braun, Rivka Zusman
  • Patent number: 5821343
    Abstract: A method is provided for immobilizing a biomolecule coating on the surface of a medical device to obtain improved biocompatibility characteristics for contacting with tissue or body fluids such as blood. The method includes oxidizing a 2-aminoalcohol moiety of a material disposed on the surface with a periodate to form an aldehyde moiety, combining the aldehyde moiety with an amine moiety of a material to bond the aldehyde moiety to the amine moiety through an imine moiety and reacting the imine moiety with a reducing agent to form the coating immobilized on the surface by an amine linkage.
    Type: Grant
    Filed: April 25, 1996
    Date of Patent: October 13, 1998
    Inventor: James R. Keogh
  • Patent number: 5817528
    Abstract: A method is provided for producing a sterile and pyrogen-free column containing coupled protein for use in removing a predetermined substance from the blood of a human subject. The method abrogates sterilization of the finished protein-containing product by providing sterile and pyrogen-free raw materials at each production step. The method provides a pathogen-free, purified solution of protein which binds to a predetermined substance in human blood such as LDL or immunoglobulin. Typically, the protein is anti-human LDL immunoglobulin or anti-human Ig immunoglobulin. The method also provides a sterile and pyrogen-free column matrix material such as an agarose which is chemically activated, either using CNBr and triethylamine or using 1,1'-carbonyldiimidazole.
    Type: Grant
    Filed: May 16, 1995
    Date of Patent: October 6, 1998
    Assignee: Therasorb Medizinische Systeme GmbH
    Inventors: Wolfgang Bohm, Franz A. Bieber, Jutta Muller-Derlich, Alan Barclay, Reiner Spaethe, Michael Bernhard, Christine Kraus
  • Patent number: 5817527
    Abstract: A new method for immobilization of small molecules on solid supports via a macromolecular spacer has been developed. A protein or another macromolecule is first immobilized in an aqueous medium, and the solid support is than washed with an organic solvent. The small molecule is coupled in an organic medium, followed by organic medium washes. The new solid phases are useful for affinity purifications, immunoassays and other binding assays, and for selection of binders by panning procedures.
    Type: Grant
    Filed: November 6, 1995
    Date of Patent: October 6, 1998
    Assignee: Chiron Diagnostics Corporation
    Inventors: Uri Piran, Steve C. S. Chang, William J. Riordan, James W. Peterson, Edward M. Sunshine
  • Patent number: 5814467
    Abstract: The present invention describes an Apo AI polypeptide capable of immunologically mimicking an Apo AI epitope. The polypeptide is useful in diagnostic methods and systems for detecting Apo AI in vascular fluid samples, and for preparation of anti-Apo AI antibodies. In addition, the polypeptide is useful in therapeutic methods for increasing esterified cholesterol in a human patient.
    Type: Grant
    Filed: August 19, 1994
    Date of Patent: September 29, 1998
    Assignee: The Scripps Research Institute
    Inventors: Linda K. Curtiss, Carole L. Banka, David J. Bonnet, Richard S. Smith
  • Patent number: 5811246
    Abstract: The invention relates to a process for immobilization onto the surface of enzyme linked immunosorbent assay (ELISA) plates of a compound or for immunization with a compound, wherein said compound is in the form of a compound carrier complex which is either an avidin-biotinyl compound complex or a streptavidin-biotinyl compound complex.
    Type: Grant
    Filed: April 25, 1994
    Date of Patent: September 22, 1998
    Assignee: The Research Foundation of State University of New York
    Inventors: Kalyan R. Anumula, Nathan N. Back
  • Patent number: 5789219
    Abstract: The present invention provides crosslinking, conjugating and reducing agents which are functional with at least one phosphorothioate monoester group (--SPO.sub.3.sup.-2). Crosslinking and conjugation methods as well as solid phase reagents and conjugates which are useful in immunoassays are also provided.Crosslinking and conjugating agents of the invention generally comprise a compound corresponding to the formula (I), shown below, wherein n at least 1 and Q is a straight or branched monomer, polymer or oligomer having an average molecular weight between about 200 and about 1,000,000. Additionally, when n is 1, Q comprises at least 1 additional reactive functionality.Q--(S--PO.sub.3 .sup.-2)n (I)The reducing agents that are provided conform to a compound of the formula (Y), shown below, wherein (A) and (Z) can be independently selected from C.sub.1 -C.sub.5 alkyl and CONH(CH.sub.2)p wherein p is an integer between 1 and 5.
    Type: Grant
    Filed: May 29, 1996
    Date of Patent: August 4, 1998
    Assignee: Abbott Laboratories
    Inventors: Christopher Bieniarz, Douglas F. Young, Michael J. Cornwell, Mazhar Husain, Zbigniew Skrzypczynski
  • Patent number: 5783627
    Abstract: An enzymatic reaction system including a modified enzyme, and a dense gas system; modified enzymes; and methods of reacting modified enzymes in a dense gas system or liquid carbon dioxide.
    Type: Grant
    Filed: September 9, 1996
    Date of Patent: July 21, 1998
    Assignee: University of Massachusetts
    Inventors: Fu-jung Kao, Kenneth E. Laintz, Samuel P. Sawan, L. Dale Sivils, W. Dale Spall
  • Patent number: 5780281
    Abstract: A method is provided for preparing a low density porous rigid fused-fiber matrix having a density of between about 3.5 and 5.5 pounds/cubic foot and a free volume of between about 90-98 volume percent for use as a cell-culture substrate or implant material, or in chromatographic separation of blood cells. The method is carried out by forming a slurry containing (I) silica, alumina or silica and alumina fibers having thicknesses between about 0.5 and 20 .mu.m and lengths between about 1 and 10 mm, and having a fiber:liquid weight ratio of between about 1:25 to 1:70, (ii) a thickening agent to give the slurry a viscosity between about 1,000 and 25,000 centipoise, (iii) boron nitride particles between about 2-12 percent by weight of the total fiber weight, and (iv) a dispersing agent when the slurry contains silica fibers, allowing the slurry to settle in a mold to produce a fiber block, drying the fiber block, and heating the dried fiber block to at least about 2200.degree. F.
    Type: Grant
    Filed: January 29, 1997
    Date of Patent: July 14, 1998
    Assignee: Lockheed Martin Corporation
    Inventors: Robert Deane Yasukawa, Loretta Jane Cordrey
  • Patent number: 5770416
    Abstract: Permeable substantially spherical hollow particles of 1-5000 .mu.m in size are formed having an outer shell of a mechanically rigid porous material. Pores of the shell are through-going pores that connect the inside of the particles to surroundings and allow chemical species to traverse the outer shell. To prepare the particles, impermeable hollow particles are treated with an acid or base under reflux conditions to form pores. The outer shell is formed of anhydrous forms of silicon dioxide, metal silicates, metal borosilicates, metal oxides or boric oxide. Metals and metal alloys are not used in forming the outer shell. Particles containing a polymer are formed by immersing the permeable hollow particles in a solution of components that polymerize to form the polymer, allowing the solution to partially fill the particles via the pores and polymerizing the components.
    Type: Grant
    Filed: June 3, 1993
    Date of Patent: June 23, 1998
    Assignee: UpFront Chromatography A/S
    Inventors: Allan Otto Fog Lihme, Thorkild Christian B.o slashed.g-Hansen, Claus Schafer Nielsen
  • Patent number: 5741686
    Abstract: A method is provided for preparing a labeled protein, immobilized protein or protein-bioactive agent composition by attaching a label, support or bioactive agent to a protein by exopeptidase catalysis at a site that is remote from the active site of the protein. More specifically, an amine or alcohol group of an amino acid, amine or alcohol nucleophile is reacted by exopeptidase catalysis with a C-terminus carboxylic acid group of a protein such as an antibody, enzyme or hormone to couple the nucleophile to the protein to form an adduct, and the adduct is bound to an auxiliary substance such as a support, label or bioactive agent or its combination with a linker arm by reacting a reactive substituent of the nucleophile with a reactive group of the auxiliary substance. Alternatively, the nucleophile is bound to the auxiliary substance or its combination with a linker arm to form an intermediate, and the intermediate is coupled by exopeptidase catalysis to the protein.
    Type: Grant
    Filed: October 3, 1994
    Date of Patent: April 21, 1998
    Assignee: Board of Regents of the University of Nebraska
    Inventors: Fred W. Wagner, Thomas R. Coolidge, Dwane E. Wylie, Sheldon M. Schuster, William Lewis, Jay Stout
  • Patent number: 5736624
    Abstract: The present invention provides crosslinking, conjugating and reducing agents which are functional with at least one phosphorothioate monoester group (--SPO.sub.3.sup.-2). Crosslinking and conjugation methods as well as solid phase reagents and conjugates which are useful in immunoassays are also provided. Crosslinking and conjugating agents of the invention generally comprise a compound corresponding to the formula (I), shown below, wherein n is at least 1 and Q is a straight or branched monomer, polymer or oligomer having an average molecular weight between about 200 and about 1,000,000. Additionally, when n is 1, Q comprises at least 1 additional reactive functionality.Q--(S--PO.sub.3.sup.-2)n (I)The reducing agents that are provided conform to a compound of the formula (Y), shown below, wherein (A) and (Z) can be independently selected from C.sub.1 -C.sub.5 alkyl and CONH(CH.sub.2).sub.p wherein p is an integer between 1 and 5.
    Type: Grant
    Filed: December 2, 1994
    Date of Patent: April 7, 1998
    Assignee: Abbott Laboratories
    Inventors: Christopher Bieniarz, Douglas F. Young, Michael J. Cornwell, Mazhar Husain
  • Patent number: 5717075
    Abstract: A solid support having surface-attached carboxylic acid groups is reacted with an isoxazolium salt to form an activated support having enol ester and sulfonate groups. After washing to remove residual isoxazolium salt and base, the activated support is dried. A polypeptide is covalently or non-covalently bound to the support. The resultant immobilized polypeptide can be conveniently sequenced by N- and C-terminal sequencing methods. The support can be a polyvinylidene difluoride membrane or a glass fiber membrane having surface attached carboxylic acid groups, and the enol and sulfonate groups are provided by reacting the support with 2-ethyl-5'-phenylisoxazolium sulfonate. The dry support can be stored for at least about 3 months to achieve a peptide immobilization yield that is substantially the same as the yield obtained in the absence of drying.
    Type: Grant
    Filed: March 28, 1996
    Date of Patent: February 10, 1998
    Assignee: The Perkin-Elmer Corporation
    Inventors: Victoria Lee Boyd, Pau-Miau Yuan
  • Patent number: 5686252
    Abstract: An immunochemical method is provided for the detection and determination of an analyte. The zeta potential of a latex-particle loaded with an immunologically active substance is measured before and after bringing the loaded latex-particle into contact with an analyte. The difference in zeta potential is correlated with changes of zeta potential for known concentrations of the analyte in order to determine the presence and amount of the analyte.
    Type: Grant
    Filed: October 23, 1995
    Date of Patent: November 11, 1997
    Assignee: Hoechst Japan Limited
    Inventor: Hiroshi Nishizaki
  • Patent number: 5665868
    Abstract: Phosvitin or a modified phosvitin immobilised and coupled to a suitable matrix may be used for the separation and purification of proteins or polypeptides and in the removal of metal ions from biological material. If desired the phosvitin or modified phosvitin may be in the form of a metal chelate complex.
    Type: Grant
    Filed: September 13, 1991
    Date of Patent: September 9, 1997
    Assignee: Vittal Mallya Scientific Research Foundation
    Inventors: Candadai Seshadri Ramadoss, Hiten Vasant Lakhey, Patnam Rajagopaliengar Krishnaswamy
  • Patent number: 5650311
    Abstract: A metod is proposed of obtaining a chemical interaction between at least one reagent trapped in sol-gel glass by doping it with the reagent(s), and diffusible solutes or components in an adjacent liquid or gas phase. The reagents, the solutes or the components can be any organic or inorganic compounds or materials of biological origins including enzymes. The doped sol-gel glass in various forms may be useful as analytical test, chromatographic medium, sensor, catalyst or biocatalyst, electrode or enzyme electrode, or other detection device.
    Type: Grant
    Filed: June 28, 1994
    Date of Patent: July 22, 1997
    Assignee: Yissum, Research Development Company of the Hebrew University of Jerusalem, Israel
    Inventors: David Avnir, Michael Ottolenghi, Sergei Braun, Rivka Zusman
  • Patent number: 5545317
    Abstract: Packing materials for liquid chromatographic or catalytic columns are prepared by contacting a porous protein-adsorptive particulate or membranous support, such as a porous silica particulate support, with an aqueous solution into which a protein has been dissolved to form a saturated coating of protein on the external surfaces of the porous protein-adsorptive support, removing excess protein that remains in solution by washing, and, then crosslinking the protein in the coating. The result is a packing material which resists further adsorption by many different proteins but which continues to provide the adsorptive or catalytic properties of the groups on the internal surfaces of the porous protein-adsorptive support for separations, analysis, or alteration of small molecules. The packing material of the present invention is particularly useful in HPLC or solid phase extraction columns for direct injection drug analysis in plasma, serum, and urine.
    Type: Grant
    Filed: April 17, 1995
    Date of Patent: August 13, 1996
    Assignee: Dow Corning Corporation
    Inventor: Dwight E. Williams
  • Patent number: 5514559
    Abstract: Novel conjugate of the general formulaA--L.sub.1 --L.sub.2 --Bwherein A and B are the substances to be coupled selected from the groups of haptens, proteins, polysaccharides, soluble polystyrenes, or peptides, L.sub.1 and L.sub.2 are trivalent linkers and L.sub.1 and L.sub.2 are bound via two thioether. They can be used in immunological assays and exhibit an improved storage stability.
    Type: Grant
    Filed: March 29, 1994
    Date of Patent: May 7, 1996
    Assignee: Boehringer Mannheim GmbH
    Inventors: Christine Markert-Hahn, Beatus Ofenloch-Haehnle, Eva Hoess, Erasmus Huber
  • Patent number: 5512169
    Abstract: Packing materials for liquid chromatographic or catalytic columns are prepared by contacting a porous protein-adsorptive particulate or membranous support, such as a porous silica particulate support, with an aqueous solution into which a protein has been dissolved to form a saturated coating of protein on the external surfaces of the porous protein-adsorptive support, removing excess protein that remains in solution by washing, and, then crosslinking the protein in the coating. The result is a packing material which resists further adsorption by many different proteins but which continues to provide the adsorptive or catalytic properties of the groups on the internal surfaces of the porous protein-adsorptive support for separations, analysis, or alteration of small molecules. The packing material of the present invention is particularly useful in HPLC or solid phase extraction columns for direct injection drug analysis in plasma, serum, and urine.
    Type: Grant
    Filed: December 30, 1992
    Date of Patent: April 30, 1996
    Assignee: Dow Corning Corporation
    Inventor: Dwight E. Williams
  • Patent number: 5494815
    Abstract: Biochemical substances, such as enzymes, are immobilized using an olefinic-unsaturated, epoxyfunctional polysiloxane. The polysiloxane is applied to a carrier material. The polysiloxane on the carrier is cross-linked by using high-energy radiation or a peroxide to form a polymer matrix. The polymer matrix is treated with an aqueous solution of a biochemical substance that reacts with epoxy groups and becomes immobilized. The polymer matrix is stabilized by the reaction of non-reacted epoxy groups with a compound containing an amino group, a carboxyl group or an amino group and a carboxyl group. The crosslinked polysiloxane can be hydrophilized after cross-linking and prior to immobilization of the biochemical substance by the reaction of a portion of the epoxy groups with a hydrophilic compound.
    Type: Grant
    Filed: March 22, 1993
    Date of Patent: February 27, 1996
    Inventors: Wolfgang von Gentzkow, Hans-Dieter Feucht, Helmut Formanek, Gerhard Wanner
  • Patent number: 5466749
    Abstract: Graft copolymers comprising a poly-alpha-olefin base polymer selected from the group consisting of polyethylene, polypropylene, polystyrene, and compatible mixtures thereof, having grafted thereto an olefinic monomer. The grafted monomer is present in an amount effective to increase the amount of protein that will bind to the graft copolymer as compared with the base polymer.Also disclosed are polymer/protein compositions comprising a graft copolymer having a protein immobilized on the surface thereof, processes for the preparation of the above-described graft copolymers and compositions, methods of immobilizing proteins, and methods of immunoassay based on such immobilization.
    Type: Grant
    Filed: September 14, 1994
    Date of Patent: November 14, 1995
    Assignee: Minnesota Mining and Manufacturing Company
    Inventors: Richard J. Rolando, Patrick L. Coleman, Steven L. Kangas, Thomas A. Kotnour
  • Patent number: 5437861
    Abstract: This invention provides a composition, device and method for the treatment or prevention of septic shock syndrome or other conditions evidenced by the presence of cytokines in a patient by contacting the patient's whole blood with a composition comprising silica and a surface treatment material, such as heparin, but preferably human serum albumin (HSA). The treatment lowers the cytokine concentration of the blood.
    Type: Grant
    Filed: March 16, 1993
    Date of Patent: August 1, 1995
    Assignee: Applied Immune Sciences, Inc.
    Inventors: Thomas B. Okarma, John Blankenship, Abraham T. Lin, Mohammad A. Elkalay
  • 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: 5362859
    Abstract: An affinity support having an improved capacity for binding target compounds. The support includes an immobilized modified ligand of increased molecular weight. The molecular weight of the ligand is increased via the action of condensation reagents or crosslinkers prior to immobilization. The affinity support is useful in affinity separations of proteins and other biomolecules from complex, biologically-derived fluids.
    Type: Grant
    Filed: July 27, 1992
    Date of Patent: November 8, 1994
    Assignee: Sepracor, Inc.
    Inventor: Stephen E. Zale
  • Patent number: 5352772
    Abstract: A new cellular protein produced by activated T cells and involved in the high affinity binding of interleukin-2 has been discovered. This protein has a molecular weight of about 75,000 (Mr) and is further characterized as having an affinity for IL-2 (in the absence of other receptor proteins) of about 10.sup.-9 molar and is substantially unreactive with anti-Tac antibodies. This new cellular protein, referred to herein as the ".alpha. chain," is believed to interact with the previously isolated 55,000 dalton receptor protein (referred to herein as the ".beta. chain") to form the high affinity interleukin-2 receptor which triggers the growth and mitosis of T cells during an immune response. Methods for isolating and purifying the .alpha. chain protein are disclosed herein as well as techniques for cloning and expressing the protein and related materials. Techniques for raising monoclonal antibodies to such proteins are also disclosed.
    Type: Grant
    Filed: December 19, 1986
    Date of Patent: October 4, 1994
    Assignees: The Trustees of Dartmouth College, United States of America
    Inventor: Kendall A. Smith
  • Patent number: 5342585
    Abstract: An apparatus is disclosed for performing a multiple synthesis of peptides on a solid carrier. Active components are successively bonded to functional groups anchored on a carrier. The carrier comprises a planar porous material divided into functionalized compartments, into which an active component is put, via a dispensing head.
    Type: Grant
    Filed: December 14, 1992
    Date of Patent: August 30, 1994
    Assignee: Academy of Sciences of the Czech Republic
    Inventors: Michal Lebl, Jutta Eichler, Vit Pokorny, Jiri Jehnicka, Petr Mudra, Karel Zenisek, Alena Stierandova, Jan Kalousek, Jan Bolf
  • Patent number: 5336760
    Abstract: The invention provides an apparatus and method for the preparation of a pharmaceutical composition comprising a complex of an antigen component and the corresponding antibody component in a pharmacologically acceptable carrier. The apparatus comprises a housing chamber for containing paramagnetic particles and a platform against which the housing chamber is releasably retained. The platform contains one or more magnets located adjacent to the housing chamber when the housing chamber is positioned on the platform. The platform is secured to a support which allows the platform, and thus the housing chamber, to be rotated between a vertical and a horizontal position.
    Type: Grant
    Filed: March 12, 1992
    Date of Patent: August 9, 1994
    Assignee: Baxter International Inc.
    Inventors: R. Alan Hardwick, Alan K. Smith, William C. Lake, Dennis E. Chenoweth
  • 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: 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: 5258453
    Abstract: 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: Grant
    Filed: January 21, 1992
    Date of Patent: November 2, 1993
    Assignee: University of Utah
    Inventors: Jindrich Kopecek, Nancy L. Krinick
  • Patent number: 5254672
    Abstract: The invention relates to synthetic peptides which contain certain partial sequences from factor VIIa, the synthesis thereof and the use of these peptides for immunizing an animal and for purifying specific antibodies against the said peptides, to antibodies against these peptides and the use of these antibodies and peptides in therapy and diagnosis.
    Type: Grant
    Filed: March 11, 1991
    Date of Patent: October 19, 1993
    Assignee: Behringwerke Aktiengesellschaft
    Inventors: Hermann Pelzer, Werner Stuber
  • 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: 5219926
    Abstract: 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: Grant
    Filed: September 13, 1991
    Date of Patent: June 15, 1993
    Assignee: Berol Nobel AB
    Inventors: Bjorn Lindman, Martin Malmsten, Krister Holmberg, Carina Andren
  • Patent number: 5162503
    Abstract: Methods are provided for the purification of interleukin-2 (IL-2) from a wide variety of sources, including synthetic mixtures, culture medium conditioned by natural IL-2 producing cells, and mammalian and bacterial recombinant IL-2 expression systems. The methods of the invention employ IL-2 receptor-affinity adsorbents in which soluble IL-2 receptors have been immobilized on solid supports. Through the use of these affinity adsorbents, highly purified IL-2 can be produced in a single step from bacterial extracts or conditioned medium. The IL-2 thus purified is largely free of aggregated forms, which are often present when other purification methods are used.
    Type: Grant
    Filed: May 19, 1987
    Date of Patent: November 10, 1992
    Assignee: Hoffmann-La Roche, Inc.
    Inventors: Pascal Bailon, John E. Smart, David V. Weber
  • Patent number: 5153166
    Abstract: 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: Grant
    Filed: August 18, 1988
    Date of Patent: October 6, 1992
    Assignee: Trustees of AT Biochem
    Inventors: Tikam Jain, Robert Shorr
  • Patent number: 5149788
    Abstract: Methods are provided for the purification of interleukin-2 (IL-2) and chimeric proteins containing an IL-2 moiety from a wide variety of sources, including synthetic mixtures, cell culture conditioned medium and mammalian and bacterial recombinant expression systems. The methods of the invention employ IL-2 receptor-affinity adsorbents in which soluble IL-2 receptors have been immobilized on solid supports. Through the use of these affinity adsorbents, highly purified IL-2 and chimeric proteins containing an IL-2 moiety can be produced in a single step from bacterial extracts or conditioned medium. The proteins thus purified are largely free of aggregated forms, which are often present when other purification methods are used.
    Type: Grant
    Filed: October 24, 1988
    Date of Patent: September 22, 1992
    Assignee: Hoffmann-La Roche, Inc.
    Inventors: Pascal Bailon, John E. Smart, David V. Weber
  • Patent number: 5141648
    Abstract: 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: Grant
    Filed: March 29, 1991
    Date of Patent: August 25, 1992
    Assignee: NeoRx Corporation
    Inventors: Mark D. Hylarides, Ananthachari Srinivasan, Jeffrey N. Fitzner, Vivekananda M. Vrudhula
  • Patent number: 5122450
    Abstract: 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: Grant
    Filed: August 20, 1987
    Date of Patent: June 16, 1992
    Assignee: Research Corporation Limited
    Inventors: Ten Feizi, Ping W. Tang
  • Patent number: 5079155
    Abstract: 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: Grant
    Filed: September 28, 1989
    Date of Patent: January 7, 1992
    Assignee: E. I. du Pont de Nemours and Company
    Inventors: Geoffrey B. Cox, Robert K. Kobos