Peptides Or Proteins Is Immobilized On, Or In, An Organic Carrier Patents (Class 530/812)
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Patent number: 5766908Abstract: An affinity support is provided containing a high flux semipermeable hydrogel membrane surface-modified with an affinity ligand, such as a protein which may be an antibody or enzyme, or a cell receptor complement, useful for affinity separation of biological macromolecules, including insoluble proteins, cells, and cell fragments, from solution. The exclusion limit (molecular weight cut-off) of the matrix is selected to substantially restrict immobilized protein or other ligand to the surface thereof for maximization of available ligand binding capacity. The exclusion limit is also selected to permit reagent(s) used for the matrix/ligand linkage to penetrate into and form covalent bonds with the membrane on the interior surfaces of the membrane for optimizing packing densities of the affinity ligand exterior to the membrane.Type: GrantFiled: January 3, 1997Date of Patent: June 16, 1998Assignee: Akzo Nobel NVInventors: Elias Klein, Donald H. Yeager
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Patent number: 5753611Abstract: Use of .alpha.-hydroxy acids and poly-.alpha.-hydroxy acids as spacer between a therapeutically and/or diagnostically active compound and a soluble macromolecular carrier in pharmaceutical compositions having site-specific delivery. In one embodiment glycolic acid, L-lactic acid or tetra-L-lactic acid is used as spacer between a non-steroidal anti-inflammatory substance and a carrier of low molecular protein (LMWP).Type: GrantFiled: November 4, 1994Date of Patent: May 19, 1998Assignee: Rijksuniversiteit GroningenInventors: Erik J. F. Franssen, Frits Moolenaar, Dirk K. F. Meijer, Dick De Zeeuw
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Patent number: 5741686Abstract: 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: GrantFiled: October 3, 1994Date of Patent: April 21, 1998Assignee: Board of Regents of the University of NebraskaInventors: Fred W. Wagner, Thomas R. Coolidge, Dwane E. Wylie, Sheldon M. Schuster, William Lewis, Jay Stout
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Patent number: 5726243Abstract: A triple-helical polypeptide of the formula: ##STR1## is provided wherein: Z is Hyp or Pro; each X and Y is an amino acid such that (Gly-X-Y).sub.m is a sequence of a collagen cell adhesion site; said X and Y may be the same or different and each (Gly-X-Y) may be the same or different; O is an amino acid having a single side-chain amino group; J is an amino acid capable of acting as a chromophore; U is an amino acid; u=0 or 1; n.ltoreq.30; m.ltoreq.30; m+n.ltoreq.30; and j.gtoreq.1. Methods of making these compounds and intermediates used in the methods, are also provided.Type: GrantFiled: July 3, 1996Date of Patent: March 10, 1998Assignee: Regents of the University of MinnesotaInventor: Gregg B. Fields
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Patent number: 5691447Abstract: Disclosed are immunogens and peptides based on the binding site of gC1q-R for HIV-1 gp120, and immunogens and peptides based on the binding site of HIV-1 gp120 for gC1q-R. The sequence of the gC1q-R binding site for gp120 is shown in SEQ ID NO.: 2. The sequence of the HIV-1 gp120 binding site for gC1q-R is shown in SEQ ID NO.: 3. Also disclosed are antibodies and binding molecules to all such immunogens and peptides, and inducing the endogenous production of such antibodies.Type: GrantFiled: March 24, 1995Date of Patent: November 25, 1997Assignee: Tanox Biosystems, Inc.Inventors: Michael S. C. Fung, Bill N. C. Sun, Cecily R. Y. Sun, Young Woo Kim, Liming Yu
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Patent number: 5686252Abstract: 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: GrantFiled: October 23, 1995Date of Patent: November 11, 1997Assignee: Hoechst Japan LimitedInventor: Hiroshi Nishizaki
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Patent number: 5670624Abstract: Protein is two-dimensionally aggregated and fixed to produce a functional thin film. A denatured film of a first protein is formed on the surface of a substrate solution such as an aqueous sugar or salt solution. A solution of a second protein which may be the same as or different from the first protein is then injected below the surface of the substrate solution at a distance sufficient not to disturb the surface. The substrate solution has a higher surface tension and specific gravity than the second protein solution causing the second protein to float between the denatured protein film and the substrate solution surface to form the two-dimensionally aggregated and fixed protein. The denatured film of first protein may be formed by injection of a solution of the first protein below the surface of the substrate solution. The aggregated and fixed protein can be heated and then transferred onto a solid surface such as in the formation of a biosensor.Type: GrantFiled: September 20, 1995Date of Patent: September 23, 1997Assignee: Research Development Corporation of JapanInventors: Hideyuki Yoshimura, Kuniaki Nagayama
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Patent number: 5665868Abstract: 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: GrantFiled: September 13, 1991Date of Patent: September 9, 1997Assignee: Vittal Mallya Scientific Research FoundationInventors: Candadai Seshadri Ramadoss, Hiten Vasant Lakhey, Patnam Rajagopaliengar Krishnaswamy
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Patent number: 5661019Abstract: A trifunctional conjugate is providing 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 moieties sterically inhibits the binding of a different macromolecule to another chemical moieties. In another embodiment, the binding of a first chemical moiety to a macromolecule restricts the subsequent binding of a second tridentate member to a proximate location on the same macromolecule. The three chemical moieties are preferably a nitrophenylazido residue, a phenyl boronic acid residue, and a solid support or a label such as biotin. The spacer is preferably cysteine, lysine, glutamic acid, pyroglutamic acid, S-acetylmercaptosuccinic anhydride or .omega.-carbobenzoxylysine.Type: GrantFiled: March 22, 1995Date of Patent: August 26, 1997Assignee: Beckman Instruments, Inc.Inventors: Chan S. Oh, James C. Sternberg
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Patent number: 5658894Abstract: Polyionic derivatives of cyclodextrins and methods for preparing these derivatives are provided in which a polyionic derivative of cyclodextrin is combined with a growth factor, preferably a heparin binding growth factor. These compositions are of low solubility and are applied directly to the location of a wound. By virtue of the low solubility, the compositions remain in place at the site of application and slowly release growth factor. In an alternative embodiment, the cyclodextrin derivatives are administered in the absence of growth factor and are used to absorb growth factor present in the body at the location of the wound in order to prevent overstimulation of the wound response.Type: GrantFiled: November 23, 1994Date of Patent: August 19, 1997Assignee: The Trustees of the University of PennsylvaniaInventor: Paul B. Weisz
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Patent number: 5656450Abstract: A latent growth factor such as transforming growth factor beta (TGF.beta.) is converted to active form by matrix vesicles or an extract from matrix vesicles. The matrix vesicles may be stimulated with a Regulator of Enhancing Factor (REF) such as 1,25-dihydroxy vitamin D (1,25-(OH).sub.2 D.sub.3) or steroid hormones which may be intercalated into the vesicle membrane. The latent growth factor may be activated in culturing cells such as chondrocytes that have been pretreated with 24,25-(OH).sub.2 D.sub.3 to activate cell differentiation, or in healing of bone or cartilage defects, and activation can be carried out in vivo or in vitro. Biodegradable polymeric implants may be prepared containing latent growth factor, REF, matrix vesicle or matrix vesicle extract.Type: GrantFiled: May 27, 1994Date of Patent: August 12, 1997Assignee: Board of Regents, the University of Texas SystemInventors: Barbara D. Boyan, Zvi Schwartz, Lynda F. Bonewald
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Patent number: 5652333Abstract: Disclosed are immunogens and peptides based on the binding site of gC1q-R for HIV-1 gp120 and immunogens and peptides based on the binding site of HIV-1 gp120 for gC1q-R. The sequence of the gC1q-R binding site for gp120 is shown in SEQ ID NO.: 2. The sequence of the HIV-1 gp120 binding site for gC1q-R is shown in SEQ ID NO.: 3. Also disclosed are antibodies and binding molecules to all such immunogens and peptides, and inducing the endogenous production of such antibodies.Type: GrantFiled: September 6, 1996Date of Patent: July 29, 1997Assignee: Tanox Biosystems, Inc.Inventors: Michael S. C. Fung, Bill N. C. Sun, Cecily R. Y. Sun, Young Woo Kim, Liming Yu
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Patent number: 5650489Abstract: The instant invention provides a library of bio-oligomers of defined size and known composition, in which the library contains all of the possible sequences of the bio-oligomers, and a method of synthesis thereof. The bio-oligomers of the library may be peptides, nucleic acids, or a combination of the foregoing. The instant invention also provides methods to identify bio-oligomers from a library that demonstrate desired characteristics such as binding, bioactivity and catalytic activity. Thus the instant invention provides a unique and powerful method to identify a useful bio-oligomer sequences from a library more quickly than current state-of-the-art technology allows. Effector molecules for use in treatment or diagnosis of disease are also provided.Type: GrantFiled: June 19, 1991Date of Patent: July 22, 1997Assignee: The Arizona Board of RegentsInventors: Kit Sang Lam, Sydney E. Salmon
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Patent number: 5643764Abstract: A reagent such as a heat resistant enzyme is entrapped in a material such as wax or a liposome that releases the reagent when heated so the reagent is available for reaction. In a preferred embodiment, wax beads containing the reagent are prepared by injecting the reagent into beads of molten wax and cooling to solidify the wax. In another embodiment, droplets of a solution of the reagent are dropped through a layer of molten wax to coat the droplets with the wax and the coated droplets are cooled to solidify the wax. The entrapped reagents have application in nucleic acid hybridizations, polymerase chain reactions (PCR), reverse transcriptase reactions (RTR), nucleic acid sequencing, and product generating reactions such as colorimetic, fluorometric and chemiluminescent enzyme labeled immunoassays.Type: GrantFiled: March 1, 1995Date of Patent: July 1, 1997Inventors: Kenneth M. Kosak, Matthew K. Kosak
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Patent number: 5641865Abstract: An interaction system, including an antibody or, antibody fragment having functional capability, which comprises a surfactant-stabilized microheterogeneous dispersion of aqueous phase in a water-immiscible medium, said aqueous phase containing an amount of said antibody or said fragment in a functional state sufficient to effect the interaction; and methods for making and for using said system.Type: GrantFiled: January 28, 1994Date of Patent: June 24, 1997Assignee: IGEN, Inc.Inventors: Charles N. Durfor, Richard J. Bolin, Allen R. Schantz, II, Richard J. Massey
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Patent number: 5624797Abstract: HIV-1 peptides having at least one point mutation between position 593 and 611 of the HIV-1 gp160 amino acid sequence. The point mutation either is at position 604 or 610, or both positions. Immunoassays which utilize these peptides are provided, as well as, diagnostic test kits which contain these peptides.Type: GrantFiled: June 7, 1995Date of Patent: April 29, 1997Assignee: Abbott LaboratoriesInventors: Dominique P. Bridon, Isaac S.-Y. Sze, deceased, David J. Daghfal, Keeve D. Jaffe, Tracey L. Colpitts
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Patent number: 5585248Abstract: A method for assaying an activity of a prophenoloxidase activating enzyme (PPAE), comprising assaying at least X-Arg or Y produced upon contact of the PPAE with a peptide chain of the formulaX-Arg-Ywherein X is an optionally labeled amino acid residue or peptide residue, having an optionally protected .alpha.-amino group or N-terminal, provided that the amino acid residue adjoining Arg is not Gly or Ala, and Y is an organic residue capable of binding to a carboxyl group of Arg by acid amide bonding or ester bonding, or an optionally labeled amino acid residue or peptide residue, having an optionally protected .alpha.-carboxyl group or C-terminal, the peptide chain capable of being hydrolyzed into X-Arg and Y by a PPAE derived from an insect. According to the present invention, PPAE activity can be quantitatively assayed with precision and a highly precise method for determining .beta.-1,3-glucan and/or peptidoglycan, wherein said PPAE activity is used as an index, can be provided.Type: GrantFiled: November 17, 1994Date of Patent: December 17, 1996Assignee: Wako Pure Chemical Industries, Ltd.Inventors: Masaaki Ashida, Tomohisa Kawabata, Kazunari Hirayasu, Masakazu Tsuchiya
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Patent number: 5583198Abstract: Compounds in which peptides, amino acids, or derivatives of these compounds are conjugated to fatty acids, including ethanolamine and tromethamine. The fatty acids facilitate the therapeutic use of the compounds by enhancing immunogenic properties of the compounds, enhancing absorption of the peptide-fatty acid conjugates and providing slow release delivery of the compounds.Type: GrantFiled: February 28, 1995Date of Patent: December 10, 1996Assignee: Commonwealth Scientific and Industrial Research OrganizationInventor: Robert G. Whittaker
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Patent number: 5578709Abstract: A macromolecular microparticle composition formed by dehydrating an aqueous macromolecule solution and crosslinking the dehydrated macromolecules with a crosslinking agent while in a liquid phase or with heat. Preferably, the dehydrating agent is a polymer mixture of polyvinylpyrrolidone and polyethylene glycol, the crosslinking reagent is glutaraldehyde, and the macromolecule is a protein, most preferably an immunoglobulin. Methods of use for research, diagnostics and therapeutics are also provided.Type: GrantFiled: March 4, 1994Date of Patent: November 26, 1996Assignee: Middlesex Sciences, Inc.Inventor: James E. Woiszwillo
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Patent number: 5559210Abstract: A Position 1 immunogen having the following formula: ##STR1## wherein: (a) P represents an immunogenic carrier material(b) X represents a linking moiety wherein --X--P is attached to a testosterone derivative(c) n is from 1 to 10, inclusive(d) the degree of substitution of P by the testosterone derivative is from 1 to 100%, inclusive.Type: GrantFiled: April 28, 1995Date of Patent: September 24, 1996Assignee: Abbott LaboratoriesInventors: Maciej Adamczyk, Yon-Yih Chen, John A. Walling, Bryan D. James, Sharon G. Artip
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Patent number: 5550044Abstract: Droplets of molten wax or waxy polymer containing a reagent are dropped onto the surface of liquid nitrogen, the droplets remain on the surface until solidified and the droplets are removed from the surface before they sink into the liquid nitrogen to provide beads containing the reagent. The reagent can be any material that can be entrapped in the beads and does not undergo excessive inactivation when the beads are melted by heating to release the reagent. Examples of reagents are heat resistant enzymes, enzyme substrates, metal salts, oligonucleotides, inclusion compounds, surfactants, emulsifiers, antioxidants, stabilizers, drugs, antibiotics, antibodies and antigens. An apparatus for producing the beads contains a plurality of channels through which liquid nitrogen flows from a reservoir. Each channel passes under a dispenser tip from which droplets are formed and released onto the surface of flowing liquid nitrogen.Type: GrantFiled: June 10, 1994Date of Patent: August 27, 1996Inventors: Kenneth M. Kosak, Matthew K. Kosak
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Patent number: 5516766Abstract: Polyionic derivatives of cyclodextrin polymers and cyclodextrins immobilized on a solid surface are disclosed. Compositions and methods for separating a molecular species, including but not limited to a biologically active protein, from a mixture, for the storage of protein factors and for the therapeutic biodelivery of protein factors which employ the polyionic derivatives of cyclodextrin polymers and cyclodextrins immobilized on a solid surface are also disclosed.Type: GrantFiled: November 12, 1993Date of Patent: May 14, 1996Assignee: The Trustees of the University of PennsylvaniaInventors: Paul B. Weisz, Yuen W. Shing, Judah Folkman
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Patent number: 5512169Abstract: 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: GrantFiled: December 30, 1992Date of Patent: April 30, 1996Assignee: Dow Corning CorporationInventor: Dwight E. Williams
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Patent number: 5484894Abstract: A macromolecular microparticle composition formed by dehydrating an aqueous macromolecule solution and crosslinking the dehydrated macromolecules with a crosslinking agent while in a liquid phase or with heat. Preferably, the dehydrating agent is a polymer mixture of polyvinylpyrrolidone and polyethylene glycol, the crosslinking reagent is glutaraldehyde, and the macromolecule is a protein, most preferably an immunoglobulin. Methods of use for research, diagnostics and therapeutics are also provided.Type: GrantFiled: March 4, 1994Date of Patent: January 16, 1996Assignee: Middlesex Sciences, Inc.Inventor: James E. Woiszwillo
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Patent number: 5470573Abstract: The invention concerns a carrier-bound recombinant protein obtainable by expression of a fusion protein gene in gram-negative bacteria which codes for at least one hydrophobic non-lytically active protein domain capable of membrane integration as well as the recombinant protein and of a gene which codes for a lytically active membrane protein from bacteriophages or a lytically active toxin release gene or lytically active partial sequences thereof and isolation of the carrier-bound recombinant protein from the culture broth. The recombinant protein is thereby firmly incorporated into the cell wall complex of gram-negative bacteria via a target sequence. Furthermore the invention concerns a recombinant DNA for the production of the protein, the production process as well as the use of carrier-bound recombinant proteins according to the present invention for immunization and as vaccines.Type: GrantFiled: September 30, 1992Date of Patent: November 28, 1995Assignee: Boehringer Mannheim GmbHInventors: Werner Lubitz, Michael P. Szostak
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Patent number: 5466609Abstract: The invention relates generally to colloidal particle having a core material and a gelatin/aminodextran coating with pendent functional groups attached thereto. Biological substances or molecules, especially monoclonal antibodies, may be attached to said particles. The monoclonal antibody containing particles are useful in a variety of positive and negative biological assays.Type: GrantFiled: October 29, 1992Date of Patent: November 14, 1995Assignee: Coulter CorporationInventors: Olavi Siiman, Alexander Burshteyn, Ravinder K. Gupta
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Patent number: 5466749Abstract: 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: GrantFiled: September 14, 1994Date of Patent: November 14, 1995Assignee: Minnesota Mining and Manufacturing CompanyInventors: Richard J. Rolando, Patrick L. Coleman, Steven L. Kangas, Thomas A. Kotnour
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Patent number: 5459239Abstract: This invention discloses novel immunogenic peptide sequences, derived from the human cyclooxygenase-1 and cyclooxygenase-2 cDNAs which elicit specific non cross-reactive antibody responses. Assays are also disclosed for selectively and independently detecting cyclooxygenase-1 or cyclooxygenase-2 proteins present in a given biological sample.Type: GrantFiled: January 24, 1994Date of Patent: October 17, 1995Assignee: Merck Frosst Canada Inc.Inventors: Gary O'Neill, Philip J. Vickers, Stacia Kargman, Jillian F. Evans
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Patent number: 5449720Abstract: The invention relates to the oral delivery of peptide and protein pharmaceuticals using the vitamin B.sub.12 (VB.sub.12) uptake system, with the delivery being amplified using polymers. More particularly, the invention concerns a complex having the general formula:(V--Q).sub.n --P--(Q'--A).sub.mwhere, V is a carrier which will bind to natural intrinsic factor (IF) selected from vitamin B.sub.12 or an analogue thereof, n is the molar substitution ratio of V in the complex, and is a number from 1.0 to about 10, P is a pharmaceutically acceptable polymer, A is a pharmaceutically active substance, m is the molar substitution ratio of A in the complex, and is a number greater than 1.0 to about 1000, Q and Q' are independently a covalent bond, or a spacer compound linking V, P and A by covalent bonds.Type: GrantFiled: May 24, 1993Date of Patent: September 12, 1995Assignee: Biotech Australia PTY LimitedInventors: Gregory J. Russell-Jones, Steven W. Westwood, Alison R. Gould, Bernard V. McInerney
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Patent number: 5439829Abstract: A chelating agent is covalently bonded to a biologically active molecule such as an enzyme or antibody, the biologically active molecule is contacted with a support containing a bound transition metal ion whereby the metal ion is chelated by the chelating agent and the oxidation state of the metal ion is changed by treatment with an oxidizing or a reducing agent to provide a kinetically inert: oxidation state to immobilize the biologically active molecule on the support. The transition metal ion is preferably Co(II), Cr(II) or Ru(III) and the oxidation state of the metal ion is changed to Co(III), Cr(III) or Ru(II), respectively. The chelating agent can be iminodiacetic acid, nitrilotriacetic acid, terpyridine, bipyridine, triethylenetetraamine, biethylenetriamine, 1,4,7-triazacyclonane or a chelating peptide. Certain chelating agents can immobilize more than one biologically active molecule at a metal ion site on the support.Type: GrantFiled: January 24, 1992Date of Patent: August 8, 1995Assignees: Eli Lilly and Company, Hybritech IncorporatedInventors: Leslie D. Anderson, James A. Cook, Gary S. David, Susan M. Hochschwender, Mary S. Kasher, Michele C. Smith, Willem P. C. Stemmer
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Patent number: 5418284Abstract: 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: GrantFiled: September 3, 1993Date of Patent: May 23, 1995Assignee: Cytec Technology Corp.Inventors: Laurence W. Chang, Larry S. Anderson, David A. Ley
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Patent number: 5413924Abstract: A reagent such as an enzyme is entrapped in a material such as wax or a liposome that releases the reagent when heated. In a preferred embodiment, wax beads containing the reagent are prepared by injecting the reagent into beads of molten wax and cooling to solidify the wax. In another embodiment, droplets of a solution of the reagent are dropped through a layer of molten wax to coat the droplets with the wax and the coated droplets are cooled to solidify the wax. The entrapped reagents have application in nucleic acid hybridizations, polymerase chain reactions (PCR), reverse transcriptase reactions (RTR), nucleic acid sequencing, and product generating reactions such as colorimetic, fluorometric and chemiluminescent enzyme labeled immunoassays.Type: GrantFiled: August 27, 1992Date of Patent: May 9, 1995Inventors: Kenneth M. Kosak, Matthew K. Kosak
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Patent number: 5407833Abstract: Peptides comprising between 20 and 39 amino acids capable of reacting with antibodies against the Sm-D polypeptide. These peptides may be used in a diagnostic method to detect of antibodies against the Sm-D polypeptide in a biological sample from a person suffering from systemic lupus erythematosus.Type: GrantFiled: April 3, 1992Date of Patent: April 18, 1995Assignee: Pasteur Sanofi DiagnosticsInventors: Marc van Regenmortel, Sylviane Muller, Jean-Paul Briand, Samira Barakat, Jean-Christophe Weber
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Patent number: 5401828Abstract: The epidermal growth factor receptor (EGFR) gene is amplified in 40% of malignant gliomas and the amplified genes are frequently rearranged. The genetic alterations associated with these rearrangements are characterized in five malignant gliomas. In one tumor, the rearrangement resulted in the deletion of most of the extracytoplasmic domain of the receptor, resulting in a hybrid mRNA between new sequences and the truncated EGFR. The predicted amino acid sequence of the protein from this tumor was remarkably similar to that described for several viral erb-B oncogenes. Four other tumors were noted to have internal deletions of the EGF receptor gene. These rearrangements brought about in-frame deletions affecting either of two cysteine-rich domains in the extracytoplasmic portion of the molecule. The clonal nature of these alterations, and the fact that identical alterations were seen in more than one tumor, suggests a role for these mutant receptor proteins in tumorigenesis.Type: GrantFiled: December 15, 1992Date of Patent: March 28, 1995Assignees: The Johns Hopkins University, Duke UniversityInventors: Bert Vogelstein, Darell Bigner
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Patent number: 5374715Abstract: A method for forming a proteoliposome comprises incorporating into a liposome a membrane protein combined with a carrier. Further, a method for preparing a giant proteoliposome, comprises freezing and thawing an alkali metal salt solution containing a membrane protein and a lipid, and subsequently dialyzing against a second salt solution or a buffer solution having a lower osmotic pressure than that of said alkali metal salt solution. Further, a method for forming a proteoliposome, comprises by freezing and thawing an alkali metal salt solution containing a membrane protein combined with a carrier and a lipid.Type: GrantFiled: March 17, 1993Date of Patent: December 20, 1994Assignee: Canon Kabushiki KaishaInventors: Tsunehiro Kanno, Junji Ohyama, Masanori Sakuranaga, Hiroyoshi Kishi, Nobuko Yamamoto, Kinya Kato, Harumi Iwashita, Yasuko Tomida
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Patent number: 5366958Abstract: This invention encompasses new and substantially improved methods and compositions for delivery of therapeutic agents to specifically chosen body sites. Conjugation of fibronectin to bioactive agents or to lipids or to liposomes which entrap the bioactive agents permits immobilization of the bioactive agent when administered at collagen-, heparin-, hyaluronic acid-, fibrin/fibrinogen-, or ganglioside-rich sites. Covalent conjugation is achieved by two methods: (1) the enzymatically catalyzed cross-linkage of fibronectin to an amine containing compound, and (2) by a modified NHS method which permits formation of peptide bonds between fibronectin and lipid compounds.Type: GrantFiled: August 20, 1993Date of Patent: November 22, 1994Assignee: The Liposome Company, Inc.Inventors: Alan L. Weiner, Robert P. Lenk, Sharon S. Carpenter-Green, Michael W. Fountain
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Patent number: 5364907Abstract: 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: GrantFiled: June 2, 1993Date of Patent: November 15, 1994Assignee: Minnesota Mining and Manufacturing CompanyInventors: Richard J. Rolando, Patrick L. Coleman, Steven L. Kangas, Thomas A. Kotnour
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Patent number: 5362859Abstract: 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: GrantFiled: July 27, 1992Date of Patent: November 8, 1994Assignee: Sepracor, Inc.Inventor: Stephen E. Zale
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Patent number: 5352772Abstract: 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: GrantFiled: December 19, 1986Date of Patent: October 4, 1994Assignees: The Trustees of Dartmouth College, United States of AmericaInventor: Kendall A. Smith
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Patent number: 5350671Abstract: Immunoassays for the detection of antibodies to HCV are provided which employ "C" domain antigens. Immunoassay kits comprising such antigens are also provided.Type: GrantFiled: August 9, 1993Date of Patent: September 27, 1994Assignee: Chiron CorporationInventors: Michael Houghton, Qui-Lim Choo, George Kuo
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Patent number: 5346832Abstract: A method is described for measuring the amount of analyte present in a sample containing the analyte using a homogeneous amperometric immunoassay. The analyte is chemically bonded to a suitable carrier molecule, which is also chemically bonded to an electroactive molecule. The electroactive molecule, such as ferrocene carboxylic acid, contains a redox center which is capable of transferring a charge to an electrode. A preferred carrier molecule is bovine serum albumin (BSA), while suitable analytes include digoxin, theophylline and HCG. The immunoassay is conveniently performed by applying a voltage to a set of electrodes.Type: GrantFiled: December 18, 1992Date of Patent: September 13, 1994Assignee: Ciba Corning Diagnostics Corp.Inventors: Masuo Aizawa, Brenda D. Manning, Miki Hidaka, Laura S. Uretsky
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Patent number: 5342693Abstract: The present invention is directed to multifunctional thrombo-resistant coatings for use with biomedical devices and implants, such as a coating which includes a siloxane surface onto which a plurality of amine functional groups have been bonded. Covalently bonded to the amine functional groups are a plurality of poly(ethylene oxide) chains, such that a single poly(ethylene oxide) chain is bonded to a single amine functional group. A plurality of different bioactive molecules, designed to counteract specific blood-material incompatibility reactions, are covalently bonded to poly(ethylene oxide) chains, such that a single bioactive molecule is coupled to a single polyethylene oxide chain.The methods of manufacturing the present invention include preparing a material having a siloxane surface onto which a plurality of amine functional groups have been bonded. This is achieved by plasma etching with ammonia gas or by plasma polymerization of a siloxane monomer in the presence of ammonia gas.Type: GrantFiled: March 22, 1993Date of Patent: August 30, 1994Assignee: Cardiopulmonics, Inc.Inventors: Suzanne Winters, Kenneth A. Solen, Clifton G. Sanders, J. D. Mortensen, Gaylord Berry
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Patent number: 5338770Abstract: The present invention is directed to thrombo-resistant coatings for use with gas permeable biomedical devices and implants. The coatings include a siloxane surface onto which a plurality of amine functional groups have been bonded. Covalently bonded to the amine functional groups are a plurality of poly(ethylene oxide) chains, such that a single poly(ethylene oxide) chain is bonded to a single amine functional group. A quantity of at least one bioactive molecule designed to counteract a specific blood-material incompatibility reaction is covalently bonded to the poly(ethylene oxide) chains, such that a single bioactive molecule is coupled to a single polyethylene oxide chain.The methods of manufacturing the present invention include preparing a material having a siloxane surface onto which a plurality of amine functional groups have been bonded. This is preferably achieved by plasma etching with ammonia gas.Type: GrantFiled: April 12, 1990Date of Patent: August 16, 1994Assignee: Cardiopulmonics, Inc.Inventors: Suzanne Winters, Kenneth A. Solen, Clifton G. Sanders, JD Mortensen, Gaylord Berry
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Patent number: 5324512Abstract: The present prevention provides an effective, fast acting method of vaccination useful in suppressing gonadotropic hormone release. The vaccine utilizes LHRH conjugated at its amino terminus to a protein carrier and can be mixed with either adjuvants or detergents in order to provide an effect vaccine.Type: GrantFiled: December 26, 1990Date of Patent: June 28, 1994Assignee: The Population CouncilInventors: Anna E. Ladd, Rosemarie B. Thau, Yun-Yen Tsong
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Patent number: 5310885Abstract: The present invention provides a process for immobilizing a protein or protein containing substance. The material to be immobilized is aggregated, contacted in a liquid with a hydrophilic solid phase and the solid phase, after contact has taken place, is dried. The present invention is also concerned with the solid phase prepared by this process and with the use thereof for analytical determination.Type: GrantFiled: May 19, 1992Date of Patent: May 10, 1994Assignee: Boehringer Mannheim GmbHInventors: Josef Maier, Dieter Mangold, Reiner Schlipfenbacher
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Patent number: 5284934Abstract: The present invention provides a process for preparing a carbohydrate-binding lectin derivative for use as immune modulators or immunoconjugates. The polymer-lectin conjugate produced in accordance with the process is polyethylene glycol Ricinus communis agglutinin I (PEG-RCAI). The lectin is coupled to the polymer by activating the polymer with a coupling agent such as 1,1-carbonyldiimidazole. The polymer-lectin conjugate is biologically active, biocompatible and is expected to be substantially non-immunogenic.Type: GrantFiled: September 4, 1992Date of Patent: February 8, 1994Assignee: Health Research Inc.Inventor: Howard J. Allen, Jr.
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Patent number: 5284911Abstract: 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: GrantFiled: November 18, 1992Date of Patent: February 8, 1994Assignee: American Cyanamid CompanyInventors: Laurence W. Chang, Larry S. Anderson, David A. Ley
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Patent number: 5284910Abstract: 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: GrantFiled: July 9, 1992Date of Patent: February 8, 1994Assignee: American Cyanamid CompanyInventors: Laurence W. Chang, Larry S. Anderson, David A. Ley
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Patent number: 5279954Abstract: The invention provides a means for attaching a label, support or bioactive agent to a protein with an exopeptidase at a site that is remote from the active site of the protein. More specifically the invention is directed to a method for the attachment of an amino acid, amine and alcohol nucleophile to the carboxyl terminus of a protein. In one embodiment, a labeled nucleophile is attached to a protein such as an antibody. In other embodiments, the invention is directed to a method for the attachment of a protein to an immobilization support and to a method for the attachment of a bioactive agent to a protein.Type: GrantFiled: June 30, 1989Date of Patent: January 18, 1994Assignee: Board of Regents of the University of Nebraska and BioNebraskaInventors: Fred W. Wagner, Thomas R. Coolidge, Dwane E. Wylie, Sheldon M. Schuster, William Lewis, Jay Stout
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Patent number: 5268306Abstract: A specific binding pair is bound to an insoluble carrier for use in determining an analyte such as in an immunoassay. The carrier is coated with a first polymer containing a protein polymer having a molecular weight of at least about 20,000 and molecules of a first member of a specific binding pair. A second polymer containing a second member of the specific binding pair is bound to the first member on the carrier by binding of the first and second members of the specific binding pair. The first polymer is preferably more hydrophobic than the second polymer. The protein polymer can be prepared by cross-linking hydrophobic protein molecules of 10,000 to 700,000 molecular weight with a bifunctional or polyfunctional compound to obtain a protein polymer of 200,000 to 20,000,000 molecular weight. The second polymer can be the second member of the specific binding pair or the second member cross-linked with a linker or the second member cross-linked to a hydrophobic protein.Type: GrantFiled: December 23, 1991Date of Patent: December 7, 1993Assignee: Boehringer Mannheim GmbHInventors: Michael Berger, Arno Deger, Josef Maier