Attached To The Carrier Via A Bridging Agent Patents (Class 530/816)
  • Patent number: 8697111
    Abstract: An osteochondral plug includes a first scaffold and a second scaffold. The first scaffold may be a solid scaffold containing one or more pendant reactive functional groups. The second scaffold capable of reacting with the one or more pendant reactive functional groups of the first scaffold.
    Type: Grant
    Filed: May 12, 2010
    Date of Patent: April 15, 2014
    Assignee: Covidien LP
    Inventors: Arpan Desai, Timothy Sargeant, Atu Agawu, Joshua Stopek
  • Patent number: 8642744
    Abstract: Crosslinking reagents and methods for using the same for analysis of protein-protein interactions, are provided. The crosslinking reagents include a trifunctional scaffold that links two protein linking groups to each other and branches to link an affinity tag, where the protein linking groups can be fragmented from the scaffold. The distance between the two protein linking groups can be selected to crosslink two proteins of a protein complex via accessible amino acid residues. Also provided are crosslinked polypeptide compounds and kits that include crosslinking reagents. These reagents and methods find use in a variety of applications in which crosslinking of proteins in desired.
    Type: Grant
    Filed: October 28, 2010
    Date of Patent: February 4, 2014
    Assignee: Agilent Technologies, Inc.
    Inventors: Brian Phillip Smart, James Alexander Apffel, Jr.
  • Patent number: 8512728
    Abstract: A method for in situ formation of a medical device on biological tissue includes attaching a plurality of reactive members of a primary specific binding pair to a surface of the biological tissue, and providing a plurality of fibers having attached thereto a plurality of complementary reactive members of the primary specific binding pair, wherein upon contact of the reactive members on the surface of the biological tissue with the complimentary reactive members on the fibers, covalent bonds are formed between the reactive members and the complementary reactive members, thus adhering the fibers to the tissue. The fibers can incorporate functionalities which may cause them to bind to one another.
    Type: Grant
    Filed: February 19, 2010
    Date of Patent: August 20, 2013
    Assignee: Sofradim Production
    Inventors: Sebastien Ladet, Philippe Gravagna
  • Patent number: 8497357
    Abstract: A heterobifunctional poly(ethylene glycol) is provided having a hydrolytically degradable linkage, a first terminus comprising an acrylate group, and a second terminus comprising a target such as a protein or pharmaceutical agent or a reactive moiety capable of coupling to a target. Hydrogels can be prepared. The hydrogels can be used as a carrier for a protein or a pharmaceutical agent that can be readily released in a controlled fashion.
    Type: Grant
    Filed: April 13, 2012
    Date of Patent: July 30, 2013
    Assignee: Nektar Therapeutics
    Inventors: J. Milton Harris, Xuan Zhao
  • Patent number: 8481334
    Abstract: The invention features a method of attaching a ligand that has a free carboxyl group to a solid support by adding an amino group to the ligand to form a ligand-amino derivative, converting the ligand amino derivative to a ligand sulfhydryl derivative, attaching the ligand sulfhydryl derivative to a protein to form a ligand-linker-protein conjugate, and applying the ligand-linker-protein conjugate to the solid support. The method is particularly useful for immobilizing small molecule ligands having a free carboxyl group, such as cloxicillin, to a lateral-flow test strip, in order to make a detection zone on the test strip that exhibits a clear signal and enhanced sensitivity.
    Type: Grant
    Filed: March 31, 2008
    Date of Patent: July 9, 2013
    Assignee: Charm Sciences, Inc.
    Inventor: Steven J. Saul
  • Patent number: 7795006
    Abstract: A support carrying an immobilized selective binding substance, that the support surface has a polymer containing the structural unit represented by the following General Formula (1) in an amount of 10% or more with respect all monomer units, and a selective binding substance is immobilized on the support surface by binding to the carboxyl group formed thereon via a covalent bond: (in General Formula (1), R1, R2, and R3 each represent an alkyl or aryl group or a hydrogen atom.
    Type: Grant
    Filed: May 18, 2004
    Date of Patent: September 14, 2010
    Assignee: Toray Industries, Inc.
    Inventors: Kunihisa Nagino, Fumio Nakamura, Hitoshi Nobumasa
  • Patent number: 7635573
    Abstract: The present invention provides a new and improved method for quantitative determination and/or identification of proteins in a sample. In one aspect, the invention provides a mass spectroscopic method for comparing protein levels in two or more samples by differentially isotopically labeling each sample's proteins' N- or C-termini. In another aspect, the invention provides a mass-spectroscopic method for identifying a sample as source for a protein from a mixture of two or more samples by differentially isotopically labeling each sample's proteins' N- or C-termini.
    Type: Grant
    Filed: December 22, 2005
    Date of Patent: December 22, 2009
    Assignee: Agilent Technologies, Inc.
    Inventor: Steven M. Fischer
  • Patent number: 7635592
    Abstract: Matrix-enhancing molecules, such as TGF-?, are conjugated to or immobilized on scaffolds to increase ECM production by cells for tissue engineering, tissue regeneration and wound healing applications. The matrix-enhancing molecule is conjugated to a tether, such as polyethylene glycol (PEG) monoacrylate, for attachment to a tissue engineering or cell growth scaffold. The matrix-enhancing molecule retains activity after attachment to the scaffold, and causes cells growing in or on the scaffold to increase extracellular matrix (ECM) production, without substantially increasing proliferation of the cells, even when the scaffold additionally contains cell adhesion ligands. The increased ECM produced by the cells aids in maintaining the integrity of the scaffold, particularly when the scaffold is degradable, either by hydrolysis or by enzymatic degradation.
    Type: Grant
    Filed: August 21, 2001
    Date of Patent: December 22, 2009
    Assignee: Rice University
    Inventors: Jennifer L. West, Brenda K. Mann
  • Patent number: 7514540
    Abstract: The invention concerns a method for immobilizing biomolecules on a polymeric surface of a carrier material and a carrier material functionalized with a biomolecule according to the general formulas (IV) and (V), which can be produced according to the method, wherein P indicates the polymeric surface of the carrier material and M indicates the biomolecule bound to the linker compound via an amino group (formula IV) or a carbonyl group (formula V) and R2 has the meaning OR4 or NR4R5; R1, R4 and R5, independently of one another, indicate H, and alkyl group or an aryl group; R3 indicates H, an alkyl, an aryl, an acyl, an alkoxycarbonyl or an aryloxycarbonyl group; and the alkyl, aryl, acyl, alkoxycarbonyl and/or aryloxycarbonyl group of the radicals R1, R3, R4 and R5, independently of one another, are substituted or unsubstituted.
    Type: Grant
    Filed: December 3, 2001
    Date of Patent: April 7, 2009
    Assignee: Poly-An Gesellschaft zur Herstellung Von Polymeren Fuer Spezielle Anwendungen und Analytik mbH
    Inventors: Pablo Wessig, Jürgen Bendig, Uwe Schedler
  • Patent number: 7423117
    Abstract: The invention concerns a novel surface-functionalized carrier material with a polymeric surface and at least one linker compound according to the general formula (I), which is covalently bound to the surface. In the formula, P indicates the polymeric surface; R2 has the meaning OR4 or NR4R5 and R1, R4 and R5, independently of one another, indicate H, an alkyl group or an aryl group; R3 indicates H, an alkyl, an aryl, an acyl, an alkoxycarbonyl or an aryloxycarbonyl group; and the alkyl, aryl, acyl, alkoxycarbonyl and/or aryloxycarbonyl group of the radicals R1, R3, R4 and R5, independently of one another, are substituted or unsubstituted. The material according to the invention can be very easily produced by photochemical coupling and serves for the solid-phase synthesis of amino acids, peptides, proteins or molecules with at least one peptidic structural unit.
    Type: Grant
    Filed: December 3, 2001
    Date of Patent: September 9, 2008
    Assignee: Ploy-An Gesellschaft zur Herstellung von Polymeren Fuer Spezielle Anwendungen und Analytik mbH
    Inventors: Pablo Wessig, Jürgen Bendig, Uwe Schedler
  • Patent number: 7422865
    Abstract: The present invention provides a new and improved method for reducing the complexity of a proteomic sample, and preferably also for allowing identification of proteins in the sample. In one aspect, the invention provides a highly efficient method for identifying proteins in a proteomic sample by characterizing a single N-terminal peptide per protein. In another aspect, the invention provides a method for identifying proteins in a proteomic sample by characterizing a single C-terminal peptide per protein. In another aspect, the present invention provides a method for quantitative determination of differential protein expression and/or modification in different samples. In another aspect, the invention relates to kits useful for conveniently performing a method in accordance with the invention.
    Type: Grant
    Filed: January 13, 2003
    Date of Patent: September 9, 2008
    Assignee: Agilent Technologies, Inc.
    Inventor: Steven M. Fischer
  • Patent number: 7419600
    Abstract: Multi-armed, monofunctional, and hydrolytically stable polymers are described having the structure wherein Z is a moiety that can be activated for attachment to biologically active molecules such as proteins and wherein P and Q represent linkage fragments that join polymer arms polya and polyb, respectively, to central carbon atom, C, by hydrolytically stable linkages in the absence of aromatic rings in the linkage fragments. R typically is hydrogen or methyl, but can be a linkage fragment that includes another polymer arm. A specific example is an mPEG disubstituted lysine having the structure where mPEGa and mPEGb have the structure CH3O—(CH2CH2O)nCH2CH2— wherein n may be the same or different for polya- and polyb- and can be from 1 to about 1,150 to provide molecular weights of from about 100 to 100,000.
    Type: Grant
    Filed: August 5, 2003
    Date of Patent: September 2, 2008
    Assignee: Nektar Therapeutics AL, Corporation
    Inventors: J. Milton Harris, Francesco Maria Veronese, Paola Caliceti, Oddone Schiavon
  • Patent number: 7417021
    Abstract: A biologically active conjugate is disclosed comprising a biopolymer and a therapeutic agent joined by a disulfide bond. The conjugate, when formulated in a pharmaceutical composition with a suitable carrier, has improved in vivo stability and activity, and can be targeted to a variety of cells, tissues and organs.
    Type: Grant
    Filed: May 7, 2004
    Date of Patent: August 26, 2008
    Assignee: Genzyme Corporation
    Inventors: Pericles Calias, Robert J. Miller
  • Patent number: 7238360
    Abstract: Methods and compositions are provided for the persistent modification of cell membranes with exogenous proteins so as to alter the function of the cell to achieve effects similar to those of gene therapy, without the introduction of exogenous DNA. DNA sequences, the proteins and polypeptides embodying these sequences are disclosed for modulating the immune system. The modulations include down-regulation, up-regulation and apoptosis.
    Type: Grant
    Filed: July 2, 2001
    Date of Patent: July 3, 2007
    Assignee: Unversity of Louisville Research Foundation, Inc.
    Inventor: Haval Shirwan
  • Patent number: 7214388
    Abstract: A heterobifunctional poly(ethylene glycol) is provided having a hydrolytically degradable linkage, a first terminus comprising an acrylate group, and a second terminus comprising a target such as a protein or pharmaceutical agent or a reactive moiety capable of coupling to a target. Hydrogels can be prepared. The hydrogels can be used as a carrier for a protein or a pharmaceutical agent that can be readily released in a controlled fashion.
    Type: Grant
    Filed: October 14, 2003
    Date of Patent: May 8, 2007
    Assignee: Debio Recherche Pharmaceutique S.A.
    Inventors: J. Milton Harris, Xuan Zhao
  • Patent number: 7208299
    Abstract: The present invention is directed to a composition and method for regulating the adhesion of cells and biomolecules to hydrophobic surfaces and hydrophobic coated surfaces. The composition is a biomolecule conjugated end-group activated polymer (EGAP). The biomolecule conjugated EGAP can be put to numerous uses including cell adhesion, cell growth, cell sorting, and other biological assays.
    Type: Grant
    Filed: December 30, 2003
    Date of Patent: April 24, 2007
    Assignee: Universtiy of Utah Research Foundation
    Inventors: Karin D. Caldwell, Patrick A. Tresco, Jennifer Neff
  • Patent number: 7195913
    Abstract: Arrays including microparticles having probe and marker moieties are used for the detection of a target in a sample. Microparticles are randomly immobilized on at least a portion of a substrate. A detection scheme is performed to detect the marker associated with the microparticle and the identity of the probe, and any target bound to the probe.
    Type: Grant
    Filed: October 5, 2001
    Date of Patent: March 27, 2007
    Assignee: SurModics, Inc.
    Inventors: Patrick E. Guire, Kristin S. Taton, John V. Wall
  • Patent number: 7166304
    Abstract: A heterobifunctional poly(ethylene glycol) is provided having a hydrolytically degradable linkage, a first terminus comprising an acrylate group, and a second terminus comprising a target such as a protein or pharmaceutical agent or a reactive moiety capable of coupling to a target. Hydrogels can be prepared. The hydrogels can be used as a carrier for a protein or a pharmaceutical agent that can be readily released in a controlled fashion.
    Type: Grant
    Filed: October 14, 2003
    Date of Patent: January 23, 2007
    Assignee: Debio Recherche Pharmaceutique S.A.
    Inventors: J. Milton Harris, Xuan Zhao
  • Patent number: 7122356
    Abstract: A method for making a medical device having at least one biomolecule immobilized on a substrate surface is provided. One method of the present invention includes immobilizing a biomolecule comprising an unsubstituted amide moiety on a biomaterial surface. Another method of the present invention includes immobilizing a biomolecule on a biomaterial surface comprising an unsubstituted amide moiety. Still another method of the present invention may be employed to crosslink biomolecules comprising unsubstituted amide moieties immobilized on medical device surfaces. Additionally, one method of the present invention may be employed to crosslink biomolecules comprising unsubstituted amide moieties in solution, thereby forming a crosslinked biomaterial or a crosslinked medical device coating.
    Type: Grant
    Filed: July 15, 2003
    Date of Patent: October 17, 2006
    Assignee: Medtronic, Inc.
    Inventors: James R. Keogh, Paul V. Trescony
  • Patent number: 7087728
    Abstract: The present invention relates to the field of carbohydrate crosslinked glycoprotein crystals. Advantageously, such crosslinked glycoprotein crystals display stability to harsh environmental conditions, while maintaining the structural and functional integrity of the glycoprotein backbone. According to one embodiment, this invention relates to methods for concentrating proteins that have been modified by carbohydrates and for releasing their activity at controlled rates. This invention also provides methods for producing carbohydrate crosslinked glycoprotein crystals and methods for using them in pharmaceutical formulations, vaccines, immunotherapeutics, personal care compositions, including cosmetics, veterinary pharmaceutical compositions and vaccines, foods, feeds, diagnostics, cleaning agents, including detergents and decontamination formulations.
    Type: Grant
    Filed: December 23, 2002
    Date of Patent: August 8, 2006
    Assignee: Altus Pharmaceuticals Inc.
    Inventors: Alexey L Margolin, Chandrika P Govardhan, Kalevi J Visuri, Sinikka S Uotila
  • Patent number: 7083936
    Abstract: A composition containing polydisperse aminodextran polymer molecules is soluble in an aqueous solution at a concentration of 10 mg/ml. The molecules therein have a narrow size distribution characterized by an average molecule mean hydrodynamic diameter of greater than 115 nm, a polydispersity index of between 0.10 and 0.47, an average molecular weight (MW) greater than 3 million daltons, and an amine content of greater than 50 amines per molecule. Similar soluble compositions contain the polymer molecules with an average MW of greater than 7 million daltons. These compositions are useful in forming reagents by conjugation with proteins for labeling cells. Methods of making these compositions and reagents from conventional mixtures of aminodextran polymers involve fractionation on column chromatography.
    Type: Grant
    Filed: August 1, 2003
    Date of Patent: August 1, 2006
    Assignee: Beckman Coulter, Inc.
    Inventors: Stephen L. Ledis, Olavi Siiman, Cynthia G. Healy
  • Patent number: 7018624
    Abstract: A degradable PEG hydrogel is described that, upon hydrolysis, releases conjugates of substantially non-peptidic polymers and biologically active molecules. For example, PEG and protein conjugates can be released in vivo from the hydrogels for therapeutic application.
    Type: Grant
    Filed: March 14, 2003
    Date of Patent: March 28, 2006
    Assignee: Debio Recherche Pharmaceutique S.A.
    Inventor: J. Milton Harris
  • Patent number: 7008634
    Abstract: Described are compositions with tethered growth effector molecules, and methods of using these compositions for growing cells and tissues. Growth effector molecules, including growth factors and extracellular matrix molecules, are flexibly tethered to a solid substrate. The compositions can be used either in vitro or in vivo to grow cells and tissues. By tethering the growth factors, they will not diffuse away from the desired location. By making the attachment flexible, the growth effector molecules can more naturally bind to cell surface receptors. A significant feature of these compositions and methods is that they enhance the biological response to the growth factors. The method also offers other advantages over the traditional methods, in which growth factors are delivered in soluble form: (1) the growth factor is localized to a desired target cell population; (2) significantly less growth factor is needed to exert a biologic response.
    Type: Grant
    Filed: March 3, 1995
    Date of Patent: March 7, 2006
    Assignee: Massachusetts Institute of Technology
    Inventors: Linda G. Cima, Edward W. Merrill, Philip R. Kuhl
  • Patent number: 6960457
    Abstract: This invention provides materials and methods for the site specific attachment of virtually any moiety to a layered silicate surface. The methods involve covalently attaching the moiety to an arginine tag; and contacting the arginine tag with the layered silicate (e.g., mica) surface.
    Type: Grant
    Filed: September 3, 1998
    Date of Patent: November 1, 2005
    Assignee: Stanford University
    Inventors: James A. Spudich, Steffen Nock, Peter Wagner
  • Patent number: 6911535
    Abstract: The present invention is directed to methods for immobilizing natural or synthetic biomolecules to surfaces. The methods comprise covalently linking the natural or synthetic biomolecule to a mono- or bi-functional polymer and covalently and/or electrostatically immobilizing the biomolecule/polymer conjugate to an unmodified or modified surface. The biomolecule is an oligonucleotide, a polynucleotide, a protein, a glycoprotein, a peptide or a carbohydrate that has been modified to incorporate a single or plurality of nucleophilic groups. These groups comprise an aliphatic or aromatic amino, thiol, hydrazine, thiosemicarbazide, hydrazide, thiocarbazide, carbazide, aminooxy, a derivative of 2-hydrazinopyridine or aminoxyacetic acid or a single or plurality of electrophilic groups. The electrophilic groups comprise an aliphatic or aromatic aldehyde, ketone, epoxide, isocyanate, isothiocyanate, succinimidyl ester or cyanuric chloride or a linkable aromatic aldehyde or ketone.
    Type: Grant
    Filed: January 15, 2002
    Date of Patent: June 28, 2005
    Assignee: Solvlink Biosciences
    Inventor: David A. Schwartz
  • Patent number: 6894025
    Abstract: A poly(ethylene glycol) derivative is disclosed that is activated with a sulfone moiety for selective attachment to thiol moieties on molecules and surfaces. The activated PEG is water soluble, hydrolytically stable for extended periods, and forms hydrolytically stable linkages with thiol moieties. The linkages generally are not reversible in reducing environments. The PEG derivative is useful for modifying the characteristics of substances including modifying biologically active molecules and surfaces for biocompatibility. Methods for synthesizing the active PEG and for preparing conjugates of the active PEG and other substances, including biologically active substances, are also disclosed.
    Type: Grant
    Filed: August 25, 2003
    Date of Patent: May 17, 2005
    Assignee: Nektar Therapeutics AL, Corp.
    Inventor: J. Milton Harris
  • Patent number: 6809186
    Abstract: The present invention relates to methods for coupling labels to particular target moieties. The coupling reactions of the present invention use temporal spacing of the reactants through phase change (i.e. by rapid freezing) to control the initiation and termination of reaction. This process results in a simplified and improved method for linking labels to specific binding moieties using N-hydroxysuccinimide chemistry. The present invention further relates to kits comprising all necessary components to easily and rapidly make protein conjugates.
    Type: Grant
    Filed: December 6, 2001
    Date of Patent: October 26, 2004
    Assignee: Martek Biosciences Corporation
    Inventors: John P. Morseman, Xiangfei Zeng
  • Patent number: 6808908
    Abstract: The invention relates to porous polymeric materials, methods of making them, and applications in medical devices. A specific embodiment of the invention encompasses a material comprising a porous polyolefin substrate containing inclusions of a material to which chemical or biological moieties are attached directly or via a spacer.
    Type: Grant
    Filed: May 30, 2001
    Date of Patent: October 26, 2004
    Assignee: Porex Technologies Corporation
    Inventors: Li Yao, George Warren Greene, IV, Guoqiang Mao, Xingguo Li
  • Patent number: 6783838
    Abstract: A coated laminate having an ionic surface including a shrinkable polymeric film, an ionic coating and, optionally, a hydrogel is disclosed. A method for transferring sample molecules from a matrix to a coated laminate having an ionic surface also is disclosed.
    Type: Grant
    Filed: April 30, 2001
    Date of Patent: August 31, 2004
    Assignee: 3M Innovative Properties Company
    Inventors: Patrick L. Coleman, Kurt J. Halverson, James I. Hembre, Sanjay L. Patil, Anila Prabhu, Raj Rajagopal, Jerald K. Rasmussen, Barbara C. Swenson, Patrick S. Quint
  • Patent number: 6770220
    Abstract: Luminescent microparticles and nanoparticles are provided for use either as internal standards for referencing fluorescent signals, or as markers for detecting biomolecules. Luminescence dyes are incorporated in inert form into solid materials such that they are protected from the influence of chemical and biological compounds in aqueous sample constituents. The photophysical characteristics of the dyes (spectral characteristics, luminescence quantum efficiency, luminescence fading time and polarization) remain unaffected. The surface of the nanoparticles and microparticles can be provided with reactive surfaces in order to enable covalent coupling of biochemicals or to eliminate aggregation.
    Type: Grant
    Filed: January 15, 2002
    Date of Patent: August 3, 2004
    Assignee: Presens Precision Sensing GmbH
    Inventor: Ingo Klimant
  • Patent number: 6749865
    Abstract: A biologically active conjugate is disclosed comprising a biopolymer and a therapeutic agent joined by a disulfide bond. The conjugate, when formulated in a pharmaceutical composition with a suitable carrier, has improved in vivo stability and activity, and can be targeted to a variety of cells, tissues and organs.
    Type: Grant
    Filed: February 15, 2001
    Date of Patent: June 15, 2004
    Assignee: Genzyme Corporation
    Inventors: Pericles Calias, Robert J. Miller
  • Patent number: 6720304
    Abstract: The invention relates to conjugates comprising a D-enantiomer of a folic acid antagonist and a carrier. Furthermore, the invention relates to the production of such conjugates as well as their use.
    Type: Grant
    Filed: July 13, 2000
    Date of Patent: April 13, 2004
    Assignee: Deutsches Krebsforschungszentrum Stiftung Des Offentlichen Rechts
    Inventors: Hannsjörg Sinn, Hans-Herman Schrenk, Wolfgang Maier-Borst, Eva Frei, Gerd Stehle
  • Patent number: 6703207
    Abstract: A compound possessing physiological activity is coupled to a styrene-glycidyl methacrylate polymer through a spacer. Compounds that may be used include receptors such as proteins, and 3-[(5-(2,3-dimethoxy-6-methyl-benzoquinonyl)]-2-nonyl-2-propionic a preferred spacer is an ethylene glycol diglycidyl ether derivative. Preferably, the whole surface of the styrene-glycidyl methacrylate polymer in microsphere form is covered with glycidyl methacrylate. The microsphere may be used for isolating and detecting substances such as proteins that bind to the coupled compound.
    Type: Grant
    Filed: November 2, 2001
    Date of Patent: March 9, 2004
    Inventors: Hiroshi Handa, Haruma Kawaguchi
  • Patent number: 6677438
    Abstract: A process for attaching a polyethylene glycol compound to a macromolecule to prepare a conjugate or adduct between the polyethylene glycol compound and the macromolecule is described. The process comprises the steps of (1) preparing an activated PEG or an activated PEG derivative by incorporating an acrylic ester, an acrylic thioester or an acrylamido group into the PEG or PEG derivative; (2) reacting the activated PEG or PEG derivative with a macromolecular material comprising one or more sulphydryl groups, primary amino groups and/or secondary amino groups and (3) recovering the conjugate of the PEG or PEG derivative and the macromolecular material.
    Type: Grant
    Filed: July 21, 2000
    Date of Patent: January 13, 2004
    Assignees: University of Nottingham, Universita Degli Studi di Brescia
    Inventors: Martin Charles Garnett, Stanley Stewart Davis, Fabio Bignotti, Paolo Ferruti
  • Patent number: 6670199
    Abstract: The present invention is directed to a composition and method for regulating the adhesion of cells and biomolecules to hydrophobic surfaces and hydrophobic coated surfaces. The composition is a biomolecule conjugated end-group activated polymer (EGAP). The biomolecule conjugated EGAP can be put to numerous uses including cell adhesion, cell growth, cell sorting, and other biological assays.
    Type: Grant
    Filed: September 4, 2001
    Date of Patent: December 30, 2003
    Assignee: University of Utah Research Foundation
    Inventors: Karin D. Caldwell, Patrick A. Tresco, Jennifer Neff
  • Patent number: 6670159
    Abstract: A precursor for the construction of chelated metal conjugates which demonstrate improved assay performance and utility in minimizing non-specific binding while maintaining specificity for target molecules is disclosed. The precursor has tridentate functionality towards multivalent ions such as iron and nickel and contains a diacetyl glycine group covalently linked via an amide to a molecule such as a proteinaceous molecule providing a primary amide group for amide bond formation. The precursor is preferably prepared in monomeric form by reacting nitrilotriacetic acid or a salt thereof in an aqueous medium at an alkaline pH of at least 8 with a proteinaceous molecule containing a primary amine group in the presence of a carbodiimide. The proteinaceous molecule may be bovine serum albumin or an enzyme such as alkaline phosphatase or horseradish peroxidase.
    Type: Grant
    Filed: July 25, 2001
    Date of Patent: December 30, 2003
    Assignee: Pierce Biotechnology, Inc.
    Inventors: M. Dean Savage, Laura L. Sykaluk
  • Patent number: 6664331
    Abstract: An activated, substantially water soluble poly(ethylene glycol) is provided having of a linear or branched poly(ethylene glycol) backbone and at least one terminus linked to the backbone through a hydrolytically stable linkage, wherein the terminus is branched and has proximal reactive groups. The free reactive groups are capable of reacting with active moieties in a biologically active agent such as a protein or peptide thus forming conjugates between the activated poly(ethylene glycol) and the biologically active agent.
    Type: Grant
    Filed: November 5, 2001
    Date of Patent: December 16, 2003
    Assignee: Nektar Therapeutics AL, Corporation
    Inventors: J. Milton Harris, Antoni Kozlowski
  • Patent number: 6638725
    Abstract: The present invention provides a method capable of simultaneous processing of plural test samples for the receptor binding property of a chemical substance, which does not require immobilization of the receptor or a special device, and a reagent to be used for this method. That is a method for assaying the receptor binding property of an assay target substance is provided, the method comprising the steps of (a) competitively reacting a known concentration of a ligand and the assay target substance with a known concentration of the receptor in a solution, (b) measuring, without physically removing the ligand bound with the receptor prior to the assay, the amount of a free ligand in the solution using one or more antibodies against the ligand, and (c) determining the receptor binding property of the assay target substance using the amount of the free ligand as an index.
    Type: Grant
    Filed: January 24, 2000
    Date of Patent: October 28, 2003
    Assignee: Toyo Boseki Kabushiki Kaisha
    Inventors: Yoshihiro Soya, Shigeaki Nishii, Kazuhiro Matsui, Takuya Ishibashi, Yoshihisa Kawamura
  • Patent number: 6630577
    Abstract: A reagent having the general formula of General Formula I: wherein group Z comprises a spacer selected from an aliphatic chain up to about 6 carbon equivalents in length, an unbranched aliphatic chain of from about 6 to 18 carbon equivalents in length with at least one of an intermediate amide and a disulfide moiety, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length; wherein group R is an electrophilic or nucleophilic moiety suitable for reaction of the reagent with a biologically active species; and wherein group Q is one of nothing at all, an amide, a methyl amide, a methylene, an ether, a thioether, a methyl ether, and a methyl thioether moiety. Also, a conjugate, a bioconjugate and a method of conjugating.
    Type: Grant
    Filed: June 4, 2001
    Date of Patent: October 7, 2003
    Assignee: Prolinx, Inc.
    Inventors: Mark L. Stolowitz, Guisheng Li, Jean P. Wiley
  • Patent number: 6617142
    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: February 24, 1999
    Date of Patent: September 9, 2003
    Assignee: Medtronic, Inc.
    Inventors: James R. Keogh, Paul V. Trescony
  • Patent number: 6566409
    Abstract: A lock unimolecular micelle includes at least one engineered acceptor specifically binding a ligand (or specifically a “key” unimolecular micelle) thereto. A key unimolecular micelle comprises a core molecule and a plurality of branches extending therefrom, at least one of the branches including a shank portion extending therefrom having a terminal moiety at an end thereof for binding to a complimentary acceptor of a lock unimolecular micelle. Together, the lock and key micelles form a unit, either irreversibly or reversibly bound wherein the lock micelles is a soluble receptor engineered to specifically bind to the specifically engineered key micelle.
    Type: Grant
    Filed: May 8, 2000
    Date of Patent: May 20, 2003
    Assignee: University of South Florida
    Inventors: George R. Newkome, Charles N. Moorefield, Gregory Baker
  • Patent number: 6551598
    Abstract: Use of a CHV antigen for the preparation of a vaccine against canine herpesvirosis, which is intended to be administered to gestating bitches as close as possible to whelping, preferably during the final third of gestation, and which produces a high level of anti-CHV antibodies in gestating bitches at the time of whelping, inducing protection in the puppies by transfer of antibodies during suckling. Inactivated anti-CHV vaccine or subunit vaccines, which can be used for vaccinating gestating bitches to protect the puppies by transfer of antibodies.
    Type: Grant
    Filed: January 18, 2001
    Date of Patent: April 22, 2003
    Assignee: Merial
    Inventor: Hervé Poulet
  • Patent number: 6545132
    Abstract: A microsphere is prepared containing a compound possessing physiological activity coupled to a styrene-glycidyl methacrylate polymer through a spacer. Compounds that may be used include receptors such as proteins, and 3-[(5-(2,3-dimethoxy-6-methyl-benzoquinonyl)]-2-nonyl-2-propionic acid. A preferred spacer is an ethylene glycol diglycidyl ether derivative. Preferably, the whole surface of the styrene-glycidyl methacrylate polymer is covered with glycidyl methacrylate. The microsphere may be used for isolating and detecting substances such as proteins that bind to the coupled compound.
    Type: Grant
    Filed: November 15, 1999
    Date of Patent: April 8, 2003
    Inventors: Hiroshi Handa, Haruma Kawaguchi
  • Patent number: 6528291
    Abstract: A method is provided for preparing an active slide, including introducing a monomer containing an aldehyde group, or a mixture of a monomer containing an aldehyde group and an acidic functional group provider into a plasma chamber; and depositing the aldehyde group and acidic functional group onto the surface of an organic or inorganic matrix using plasma deposition to form a slide comprising a layer of polymerized actively functional groups thereon. The aldehyde groups and negatively charged groups are deposited on the surface of the active slide, such that the bio-molecules bound thereto possess the properties of an inducible orientation and thus form a mono-layer.
    Type: Grant
    Filed: September 11, 2000
    Date of Patent: March 4, 2003
    Assignee: Industrial Technology Research Institute
    Inventors: Zu-Sho Chow, Jia-Huey Tsao, Wen-Hsun Kuo, Chih-Wei Ho, Bor-Iuan Jan, Chao-Chi Pan, Yao-Sung Chang, Cheng-Tao Wu, Yu-Ching Liu
  • Patent number: 6514734
    Abstract: A polybifunctional reagent is provided having a polymeric backbone, one or more pendent latent reactive (preferably photoreactive) moieties, and two or more pendent bioactive groups. The reagent can be activated to form a bulk material or can be brought into contact with the surface of a previously formed biomaterial and activated to form a coating. The pendent bioactive groups function by promoting the attachment of specific molecules or cells to the bulk material or coated surface. Bioactive groups can include proteins, peptides, carbohydrates, nucleic acids and other molecules that are capable of binding noncovalently to specific and complimentary portions of molecules or cells.
    Type: Grant
    Filed: June 9, 2000
    Date of Patent: February 4, 2003
    Assignee: Surmodics, Inc.
    Inventors: David L. Clapper, Melvin J. Swanson, Sheau-Ping Hu, Richard A. Amos, Terrence P. Everson
  • Patent number: 6514688
    Abstract: Biological materials in a mixture of substances are separated, detected or quantified using magnetic spherically shaped cross-linked polyvinyl alcohol (PVAL) polymer particles ranging in size from 1 to 10 &mgr;m. The particles containing a coupled ligand are used to bind a biological material in a mixture of substances, and the particles containing bound biological material are isolated from the mixture. The particles are prepared by dispersing a magnetic colloid containing a magnetic material such as a ferromagnetic or superparamagnetic substance in an aqueous solution of polyvinyl alcohol containing reactive hydroxyl groups, adding the resultant mixture to an organic phase containing a mixture of at least two emulsifiers, and adding a water-soluble cross-linking agent such as a dialdehyde that reacts with the hydroxyl groups of polyvinyl alcohol to form the polymer particles.
    Type: Grant
    Filed: November 29, 2000
    Date of Patent: February 4, 2003
    Assignee: chemagen Biopolymer-Technologie Aktiengesellschaft
    Inventor: Detlef Muller-Schulte
  • Patent number: 6500933
    Abstract: The present invention relates to the field of carbohydrate crosslinked glycoprotein crystals. Advantageously, such crosslinked glycoprotein crystals display stability to harsh environmental conditions, while maintaining the structural and functional integrity of the glycoprotein backbone. According to one embodiment, this invention relates to methods for concentrating proteins that have been modified by carbohydrates and for releasing their activity at controlled rates. This invention also provides methods for producing carbohydrate crosslinked glycoprotein crystals and methods for using them in pharmaceutical formulations, vaccines, immunotherapeutics, personal care compositions, including cosmetics, veterinary pharmaceutical compositions and vaccines, foods, feeds, diagnostics, cleaning agents, including detergents and decontamination formulations.
    Type: Grant
    Filed: March 3, 2000
    Date of Patent: December 31, 2002
    Assignee: Altus Biologics Inc.
    Inventors: Alexey L. Margolin, Chandrika P. Govardhan, Kalevi J. Visuri, Sinikka S. Uotila
  • Patent number: 6462179
    Abstract: Reagents suitable for the modification of a bioactive species for the purpose of incorporating one or more phenyldiboronic acid (PDBA) moieties for subsequent conjugation to a different (or the same) bioactive species having one or more pendant boronic compound complexing moieties of the general formula of General Formula I, wherein group R is a reactive electrophilic or nucleophilic moiety suitable for reaction of the PDBA reagent with a bioactive species. Group Z is a spacer selected from a saturated or unsaturated chain up to about 0 to 6 carbon equivalents in length, an unbranched saturated or unsaturated chain of from about 6 to 18 carbon equivalents in length with at least one intermediate amide or disulfide moiety, and a polyethylene glycol chain of from about 3 to 12 carbon equivalents in length. Group Q is a linkage that includes one of amide, ether and thioether moieties.
    Type: Grant
    Filed: July 25, 2000
    Date of Patent: October 8, 2002
    Assignee: Prolinx, Inc.
    Inventors: Mark L. Stolowitz, Edward A. Kesicki, Kevin P. Lund, Karin A. Hughes
  • Patent number: 6458923
    Abstract: The substitution of the L-Pro at the 7-position of the peptide hormone bradykinin or other substituted analogs of bradykinin with an isoquinoline derivative which converts bradykinin agonists into bradykinin antagonists. The invention further includes the novel 7-position modified bradykinin antagonists which increase enzyme resistance, antagonist potency, and/or specificity of the new bradykinin antagonists. The analogs produced are useful in treating conditions and diseases of a mammal and human in which an excess of bradykinin or related kinins are produced or injected as by insect bites.
    Type: Grant
    Filed: September 12, 1994
    Date of Patent: October 1, 2002
    Assignee: Scios Inc.
    Inventor: Donald James Kyle
  • Patent number: 6444261
    Abstract: A particle resistant to storage of at least one first and at least one second component, wherein said second component of at least one crosslinkable polymer as a shell at least partially envelops and/or encloses said first component as a core and said first component has at least one ascertainable property, obtainable by reacting said first component with the crosslinkable polymer and subsequently reacting the formed product with a crosslinking agent such that the first component with resistance to storage remains within the second component.
    Type: Grant
    Filed: July 20, 1998
    Date of Patent: September 3, 2002
    Assignee: Abion Beteiligungs-und Verwaltungsgesellschaft mbH
    Inventors: Dmitri Plaksine, Elena Gromakovskaia, Christoph Erhardt