Carrier Is A Synthetic Polymer Patents (Class 530/815)
  • Patent number: 7153519
    Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules.
    Type: Grant
    Filed: June 25, 2003
    Date of Patent: December 26, 2006
    Assignee: Board of Regents, The University of Texas System
    Inventors: Jeffrey A. Hubbell, Chandrashekhar P. Pathak, Amarpreet S. Sawhney, Neil P. Desai, Jennifer L. Hill, Syed F. A. Hossainy
  • Patent number: 7101846
    Abstract: Compositions, and methods of use thereof, for use as blood substitute products comprise aqueous mixtures of oxygen-carrying and non-oxygen carrying plasma expanders and methods for the use thereof. The oxygen-carrying component may consist of any hemoglobin-based oxygen carrier, while the non-oxygen carrying plasma expander my consist of any suitable diluent.
    Type: Grant
    Filed: August 11, 2004
    Date of Patent: September 5, 2006
    Assignee: The Regents of the University of California
    Inventor: Robert M. Winslow
  • 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: 7011963
    Abstract: The invention relates to a process for synthesis, by inverse bead polymerization of a monomer phase, of a bead-like, cross-linked, hydrophilic copolymer which has binding activity toward ligands containing nucleophilic groups. The invention relates to support polymer materials with high binding capacity for penicillin acylase and low swelling factor, as well as to use of the same.
    Type: Grant
    Filed: February 1, 1999
    Date of Patent: March 14, 2006
    Assignee: Roehm GmbH & Co KG
    Inventors: Christian Meier, Thomas Suefke, Hans-Ulrich Petereit, Roger Recktenwald, Thomas Boller
  • 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: 6995248
    Abstract: This invention relates to a biomolecule-bound substrate made of polymeric molecules, each of which contains a reacting group; and a plurality of biomolecules, each of which contains another reacting group. One of the two reacting groups is a substitute group and the other is a leaving group; and the biomolecules are covalently bonded to the solid support via a chemical ligation reaction between the two reacting groups.
    Type: Grant
    Filed: July 16, 2001
    Date of Patent: February 7, 2006
    Assignee: Dr. Chip Biotechnology, Inc.
    Inventors: Kan-Hung Lee, Kang-Jehng Chen, Hsing Hsiao, Shin-Hwan Wang
  • Patent number: 6989147
    Abstract: Disclosed are novel proteins, referred to as tumor necrosis factor binding proteins, that modulate the activity of tumor necrosis factor. Also disclosed are processes for obtaining the tumor necrosis binding proteins by recombinant genetic engineering techniques.
    Type: Grant
    Filed: June 15, 2001
    Date of Patent: January 24, 2006
    Assignee: Amgen Inc.
    Inventors: Eric F. Fisher, Carl K. Edwards, III, Gary L. Kieft
  • 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: 6872576
    Abstract: The invention relates to an immunoassays, binding assays, solid phase substrates (12) and other devices with an antigen or antibody or ligand or receptor (11) embedded into a solid phase substrate (12). The antigen or antibody is mixed with a molten thermoplastic and formed into the solid phase substrate (12).
    Type: Grant
    Filed: March 17, 2000
    Date of Patent: March 29, 2005
    Assignee: Embedded Concepts, LLC
    Inventor: John A. McIntyre
  • Patent number: 6858582
    Abstract: Methods and reagents are provided for specifically targeting biologically active compounds such as antiviral and antimicrobial drugs, or prodrugs containing the biologically active compound to specific sites such as specific organelles in phagocytic mammalian cells. The biologically active compound or prodrug is linked to a microparticle with a linker that is non-specifically or specifically cleaved inside a phagocytic mammalian cell. Alternatively, the biologically active compound or prodrug is impregnated into a porous microparticle or coated on a nonporous microparticle, and then coated with a coating material that is non-specifically or specifically degraded inside a phagocytic mammalian cell. The prodrug contains the biologically active compound linked to a polar lipid such as ceramide with a specific linker such as a peptide that is specifically cleaved to activate the prodrug in a phagocytic mammalian cell infected with a microorganism.
    Type: Grant
    Filed: January 15, 2002
    Date of Patent: February 22, 2005
    Assignee: Oregon Health and Sciences University
    Inventors: Milton B. Yatvin, Michael HB Stowell, Vincent S. Gallicchio, Michael J. Meredith
  • Patent number: 6849594
    Abstract: The invention relates to purified cartilage oligomeric matrix protein (COMP), such as human COMP (hCOMP), including hCOMP prepared by purifying hCOMP in the presence of calcium (e.g. under calcium replete conditions); methods of purifying COMP in the presence of calcium; antibodies to purified hCOMP; ELISA kits comprising purified hCOMP; compositions (e.g.
    Type: Grant
    Filed: June 29, 2000
    Date of Patent: February 1, 2005
    Inventors: Hui Chen, John W. Lawler
  • Patent number: 6825000
    Abstract: An immunoassay reagent is obtained whereby a microscale substance such as an antigen or antibody can be assayed at a high sensitivity, and whereby a need to separate a reacted substance, e.g., an immunoreacted substance, from an unreacted substance can be eliminated or such a separation can be simplified. An immunoassay reagent, for use in the quantitative determination of a target antigen or antibody present in a sample, containing an insoluble carrier which carries an enzyme and an antibody or antigen corresponding to the antigen or antibody, an enzyme inhibitor for inhibiting the activity of the enzyme and a substrate with which the enzyme reacts.
    Type: Grant
    Filed: October 31, 2000
    Date of Patent: November 30, 2004
    Assignee: Sekisui Chemical Co., Ltd.
    Inventors: Masayuki Yokoi, Takayuki Akamine, Katsumi Yoshikawa
  • Patent number: 6821529
    Abstract: The present invention provides biotechnologically useful oligo(ethylene glycol)-terminated 1,2-dithiolane compositions and conjugates of these compositions with biological or non-biological receptor, ligand, sequestering, or reporter moieties. The invention also provides methods for the preparation of these compositions. Further, the invention provides self-assembled monolayer (SAM) compositions on a metal and methods for their preparation.
    Type: Grant
    Filed: September 5, 2001
    Date of Patent: November 23, 2004
    Inventor: Deanna Jean Nelson
  • 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: 6783962
    Abstract: The present invention relates to particulate material having a density of at least 2.5 g/ml, where the particles of the particulate material have an average diameter of 5-75 &mgr;m, and the particles of the particulate material are essentially constructed of a polymeric base matrix, e.g. a polysaccharide such as agarose, and a non-porous core material, e.g. steel and titanium, said core material having a density of at least 3.0 g/ml, said polymeric base matrix including pendant groups which are positively charged at pH 4.0 or which are affinity ligands for a bio-molecule. Possible pendant groups include polyethyleneimine (PEI), diethylaminoethyl (DEAE) and quaternary aminoethyl (QAE). The materials are useful in expanded bed or fluidized bed chromatography processes, in particular for purification of bio-macromolecules such as plasmid DNA, chromosomal DNA, RNA, viral DNA, bacteria and viruses.
    Type: Grant
    Filed: November 20, 2001
    Date of Patent: August 31, 2004
    Assignee: UpFront Chromatography
    Inventors: Morten Aae Olander, Allan Otto Fog Lihme, Timothy John Hobley, Marcos Simon, Irini Theodossiou, Owen Robert Tyrynis Thomas
  • Patent number: 6756234
    Abstract: It has been found that casein and salts of casein are useful as replacements for, or in addition to, BSA as materials for coating solid phases, particularly magnetic particles, used for immunoassays and other binding assays for separation of the desired analyte. By using casein, immunoassays having improved stability and few discordant samples have been developed. Casein used at a concentration of 0.05-4.0 grams per gram of paramagnetic particle (optimally approximately 0.78-1.2 grams of casein per gram of magnetic particle) has been found to confer this benefit. In addition, a process for coating solid phases has been invented, said process comprising the mixing of casein with magnetic particles at 30-60° C. for 5-180 hours, said process resulting in casein-coated paramagnetic particles which either (1) already have combined therewith active ingredients needed in the binding assay or (2) are capable of reacting with active ingredients needed in the binding assay.
    Type: Grant
    Filed: December 21, 2001
    Date of Patent: June 29, 2004
    Assignee: Bayer Corporation
    Inventors: Wei-Chao Ni, Daniel W. Eustace, Steve Chin-Shen Chang
  • Patent number: 6756354
    Abstract: The present invention provides biotechnologically useful oligo(ethylene glycol)-terminated 1,2-dithiolane compositions and conjugates of these compositions with biological or non-biological receptor, ligand, sequestering, or reporter moieties to provide physiologically active therapeutic compositions. The invention also provides methods for the preparation of these compositions. Further, the invention provides self-assembled monolayer (SAM) compositions on a metal and methods for their preparation.
    Type: Grant
    Filed: April 3, 2002
    Date of Patent: June 29, 2004
    Inventor: Deanna Jean Nelson
  • 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: 6693083
    Abstract: A composition for intracellular delivery of a chemical agent into an interleukin-2-receptor-bearing cell, e.g. an activated T cell, includes a chemical agent and at least one copy of an interleukin-2-receptor-binding and endocytosis-inducing ligand coupled to a water soluble polymer. The ligand binds to a receptor on the interleukin-2-receptor-bearing cell and elicits endocytosis of the composition. The composition also preferably includes a spacer for coupling the chemical agent and the ligand to the polymer. Chemical agents can include cytotoxins, transforming nucleic acids, gene regulators, labels, antigens, drugs, and the like. A preferred water soluble polymer is a polyalkylene oxide, such as polyethlene glycol and polyethylene oxide, and activated derivatives thereof. The composition can further comprise a carrier such as another water soluble polymer, liposome, or particulate. Methods of using these compositions for delivering a chemical agent in vivo or in vitro are also disclosed.
    Type: Grant
    Filed: February 12, 2001
    Date of Patent: February 17, 2004
    Assignee: Watson Pharmaceuticals, Inc.
    Inventors: Ramesh K. Prakash, Christopher M. Clemens
  • 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: 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: 6638526
    Abstract: A polypeptide-polymer conjugate is prepared having one or more polymers covalently bound to a polypeptide. The polymer has the general formula; EOXPOY wherein EO is ethylene oxide, PO is propylene oxide, x=1−99%, y=1−99%, x+y=100%, and x and y are in a ratio range of 10:90 to 90:10, more preferably 40:60 to 60:40, or in a 50/50 ratio. The polymer, which can be a block polymer, typically has a molecular weight in a range of 100 to 100,000 daltons, and the polypeptide may contain 1 to 100 polymer molecules. Coupling the polypeptide, in particular enzymes, to the polymer reduces respiratory allergenicity of the polypeptide. Industrial compositions such as detergent compositions, personal care compositions, compositions for processing/treating textiles, and food and feed compositions containing the polypeptide-polymer conjugate have reduced respiratory allergenicity.
    Type: Grant
    Filed: June 23, 1999
    Date of Patent: October 28, 2003
    Assignee: Novozymes A/S
    Inventors: Heinz-Josef Deussen, Arne Agerlin Olsen, Tine Muxoll Fatum, Erwin Ludo Roggen
  • Patent number: 6635744
    Abstract: The invention provides fibroblast growth factor homologous factor (FHF) polypeptides and nucleic acid molecules that encode them. Also included in the invention are diagnostic and therapeutic methods using FHF polypeptides and nucleic acids.
    Type: Grant
    Filed: January 25, 2000
    Date of Patent: October 21, 2003
    Assignee: The Johns Hopkins University School of Medicine
    Inventors: Jeremy Nathans, Philip M. Smallwood
  • Patent number: 6632446
    Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, and coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules.
    Type: Grant
    Filed: October 23, 2000
    Date of Patent: October 14, 2003
    Assignee: The Board of Regents, University of Texas System
    Inventors: Jeffrey A. Hubbell, Chandrashekhar P. Pathak, Amarpreet S. Sawhney, Neil P. Desai, Jennifer L. Hill, Syed F. A. Hossainy
  • 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: 6586239
    Abstract: A method is provided for obtaining a cell population enriched in microglial cells by contacting a composition containing microglial cells with immunoglobulin immobilized on a matrix such as a polystyrene matrix before or after contact with the cells, allowing the cells to bind to the with immunoglobulin, and removing non-adherent cells to obtain a cell population containing preferably at least 95% microglial cells. The immunoglobulin may be Fc domain-containing immunoglobulin G, and Fc receptors of the microglial cells bind to the Fc domain of immunoglobulin G. Purified Fc fragments from immunoglobulin G may be used in place of immunoglobulin G. The microglial cells may be from brain tissue, and from tissue of a normal animal or tissue of an animal having a neurological disorder.
    Type: Grant
    Filed: January 7, 2000
    Date of Patent: July 1, 2003
    Assignee: AGY Therapeutics, Inc.
    Inventors: Huaiyu Mi, Saili Yi
  • Patent number: 6569426
    Abstract: Viruses are modified by coupling a polymer such as polyethylene glycol to obtain polymer-modified viruses that can exhibit reduced antigenicity while retaining infectivity, and which may exhibit increased circulation time in vivo. The polymer may be directly covalently attached or indirectly covalently attached via an intermediate coupling moiety to the virus. The polymer may also be indirectly noncovalently attached to the virus via a ligand such as an antibody having specificity for a viral surface component. To prepare the polymer-modified virus, the polymer is activated and coupled to the virus. A preferred activated polymer is tresyl-monomethoxypolyethylene glycol having an average molecular weight of about 5000 daltons. The polymer-modified viruses have utility for therapeutic and diagnostic in vivo applications, and may be used to introduce a transgene into a target cell by infection, or be administered to a subject having a tumor where the polymer-modified virus localizes to the tumor.
    Type: Grant
    Filed: September 30, 1999
    Date of Patent: May 27, 2003
    Assignees: Genzyme Corporation, Polymasc Pharmaceuticals
    Inventors: Alan E. Smith, Catherine R. O'Riordan, Gillian E. Francis, Vincent Parkes, Christina Delgado
  • Patent number: 6565842
    Abstract: In accordance with the present invention, there are provided rapidly crosslinkable polypeptides which are obtained upon introduction of unsaturated group(s) into the polypeptide via linkage to amino acid residues on the polypeptide directly through one of three types of linkages, namely, an amide linkage, an ester linkage, or a thioester linkage. Each of these linkages are obtainable in a single step by use of a single derivatizing agent, acrylic anhydride. Also provided are methods for preparing such modified polypeptides and various uses therefor. It has unexpectedly been found that proteins with the above-described chemical modifications have the ability to rapidly crosslink to themselves under suitable conditions. This crosslinking occurs in the absence of any external crosslinking agents (indeed, in the absence of any extraneous agents), resulting in the formation of a solid gel material. Solid crosslinked gels are formed in seconds, starting from a freely flowing solution of polypeptide.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: May 20, 2003
    Assignee: American Bioscience, Inc.
    Inventors: Soebianto A. Sojomihardjo, Neil P. Desai, Paul A. Sandford, Patrick Soon-Shiong, Shubhi Nagrani
  • 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: 6541606
    Abstract: This invention relates to methods for the stabilization, storage and delivery of biologically active macromolecules, such as proteins, peptides and nucleic acids. In particular, this invention relates to protein or nucleic acid crystals, formulations and compositions comprising them. Methods are provided for the crystallization of proteins and nucleic acids and for the preparation of stabilized protein or nucleic acid crystals for use in dry or slurry formulations. The present invention is further directed to encapsulating proteins, glycoproteins, enzymes, antibodies, hormones and peptide crystals or crystal formulations into compositions for biological delivery to humans and animals. According to this invention, protein crystals or crystal formulations are encapsulated within a matrix comprising a polymeric carrier to form a composition.
    Type: Grant
    Filed: August 10, 1999
    Date of Patent: April 1, 2003
    Assignee: Altus Biologics Inc.
    Inventors: Alexey L. Margolin, Nazar K. Khalaf, Nancy L. St. Clair, Scott L. Rakestraw, Bhami C. Shenoy
  • 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: 6521431
    Abstract: Biodegradable cross-linkers are provided having a polyacid core with at least two acidic groups covalently connected to reactive groups usable to cross-link polymer filaments. Between at least one reactive group and an acidic group of the polyacid is a biodegradable region which preferably consists of a hydroxyalkyl acid ester sequence having 1, 2, 3, 4, 5 or 6 hydroxyalkyl acid ester groups. The polyacid may be attached to a water soluble region that is attached to the biodegradable region having attached reactive groups. The hydroxyalkyl acid ester group is preferably a lactate or glycolate. Polyacids include diacids, triacids, tetraacids and pentaacids, and the reactive group may contain a carbon-carbon double bond. A network of cross-linked polymer filaments having adefined biodegradation rate can be formed using the cross-linkers. The network may contain biologically active molecules, and can be in the form of a microparticle or nanoparticle, or hydrogel.
    Type: Grant
    Filed: June 22, 1999
    Date of Patent: February 18, 2003
    Assignee: Access Pharmaceuticals, Inc.
    Inventors: Patrick F. Kiser, Allen A. Thomas
  • 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: 6500921
    Abstract: This invention provides efficient methods for producing a covalent linkage having improved chemical stability between an amine-containing biomolecule and a solid support or hydrogel surface containing an aldehyde moiety.
    Type: Grant
    Filed: November 7, 2000
    Date of Patent: December 31, 2002
    Assignee: Amersham Biosciences AB
    Inventors: Norman Gery Fuller, W. Travis Johnson, Michael Gaskin, Peiming Zhang
  • Patent number: 6492501
    Abstract: The invention concerns a water soluble vinyl membrane-polymer protein amphiphilic complex, characterised in that said vinyl polymer corresponds to formula (I) in which: R1 is a group: COO⊖ M+ M+ being an alkaline cation, COOR7, R7 being a sugar radical; polyoxyalkylene, polyoxyethylene; N-pyrrolidonyl; phenyl sulphonate; CONR8R9, R8 and R9 identical or different being hydrogen atom, a sugar radical, polyoxyalkylene, in particular polyoxyethylene, a zwitterion radical; R4, R5, R6 identical or different are hydrogen atom, or methyl radical; R2 is a COOR12 or CONR13R14 radical, R12 being a linear or branched alkyl or alkylene radical; R13, R14 identical or different have one of the meanings of R12, and moreover one of the two can correspond to hydrogen atom; R3 is a COOR15 or CONR16R17 radical; R15 being a (C1-C5) alkyl radical; R16, R17 having one if the meanings of R15 and moreover one of the two can correspond to hydrogen atom; x, y, z correspond to the respective percentages of units.
    Type: Grant
    Filed: November 5, 1999
    Date of Patent: December 10, 2002
    Inventors: Jean-Luc Popot, Christophe Tribet, Roland Audebert
  • Patent number: 6465001
    Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, and coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules. A medical condition at a localized site is treated by applying a polymerization initiator and then applying a substantially water-soluble, degradable macromer of at least 200 mw and having at least two crosslinkable substituents, and polymerizing the macromer to form a crosslinked polymeric material at the site.
    Type: Grant
    Filed: March 3, 1998
    Date of Patent: October 15, 2002
    Assignee: Board of Regents, The University of Texas Systems
    Inventors: Jeffrey A. Hubbell, Chandrashekhar P. Pathak, Amarpreet Sawhney, Neil Desai, Syed Hossainy, Jennifer L. Hill-West
  • Patent number: 6461874
    Abstract: It has been found that casein and salts of casein are useful as replacements for, or in addition to, BSA as materials for coating solid phases, particularly magnetic particles, used in immunoassays and other binding assays for separation of the desired analyte. By using casein, immunoassays having improved stability and fewer discordant samples have been developed. Casein used at a concentration of 0.05-4.0 grams per gram of paramagnetic particle (optimally approximately 0.78-1.2 grams of casein per gram of magnetic particle) has been found to confer this benefit.
    Type: Grant
    Filed: January 26, 2000
    Date of Patent: October 8, 2002
    Assignee: Bayer Corporation
    Inventors: Wei-Chao Ni, Daniel W. Eustace, Steve Chin-Shen Chang
  • 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
  • Patent number: 6433078
    Abstract: The present invention is directed to a method for producing reversibly soluble, catalytically active enzyme-polymer conjugates and the products thereof. In particular, the invention is directed to reversibly soluble catalytically active enzyme-polymer conjugates made by incorporating enzymes modified to contain free vinyl double bonds into reversibly soluble polymers i.e., polymers that reversibly respond to slight changes in the environment, such as temperature, ionic strength, pH, electric fields, etc., during the polymerization reaction. Thus, when modified enzymes are incorporated into reversibly soluble polymers, the biocatalysts obtained can be precipitated without destroying the delicate enzyme(s). Moreover, these biocatalysts can be solubilized again and reused at the initial environmental conditions.
    Type: Grant
    Filed: October 23, 2000
    Date of Patent: August 13, 2002
    Assignee: Polium Technologies, Inc.
    Inventors: Mikhail Y. Gololobov, Victor M. Ilyashenko
  • Patent number: 6432918
    Abstract: Compositions, and methods of use thereof, for use as blood substitute products comprise aqueous mixtures of oxygen-carrying and non-oxygen carrying plasma expanders and methods for the use thereof. The oxygen-carrying component may consist of any hemoglobin-based oxygen carrier, while the non-oxygen carrying plasma expander my consist of any suitable diluent.
    Type: Grant
    Filed: April 5, 2000
    Date of Patent: August 13, 2002
    Assignee: The Regents of the University of California
    Inventor: Robert M. Winslow
  • Patent number: 6423517
    Abstract: Granules are prepared containing an admixture of protein and salt layered over an inert particle. A preferred amount of salt is about between 63.7 and 84.3% of the total weight of the admixture. Proteins include pharmaceutically important proteins such as hormones, or industrially important proteins such as enzymes including proteases, amylases, lipases and cellulases capable of hydrolyzing substrates such as stains. Inert particles include inorganic salts, sugars, sugar alcohols, small organic molecules such as organic acids or salts, and minerals such as clays or silicates. A binder such as starch or polyethylene oxide may be mixed in with the admixture. A barrier material such as an inorganic salt or organic acid or salt may be in the admixture or coated over the admixture layer. A coating layer of a soluble or water dispersible film-forming polymer may be between the inert particle and admixture layer and/or over the admixture layer.
    Type: Grant
    Filed: December 18, 1998
    Date of Patent: July 23, 2002
    Assignee: Genecor International, Inc.
    Inventors: Nathaniel T. Becker, Robert I. Christensen, Jr., Ernst H. Gros
  • Publication number: 20020071908
    Abstract: A particle resistant to storage of at least one first and at least one second component, wherein
    Type: Application
    Filed: July 20, 1998
    Publication date: June 13, 2002
    Inventors: DMITRI PLAKSINE, ELENA GROMAKOVSKAIA, CHRISTOPH ERHARDT
  • Patent number: 6399750
    Abstract: A separation medium having a base matrix and matrix-bound groups which exhibit recombinant Protein A containing a cysteine. The groups are of formula: —B—X—rProtein A-cys where B is a bridge which binds to the base matrix and X includes a heteroatom N or S from rProtein A-cys. In a preferred embodiment X is a thioether sulphur and/or a secondary amine (—NH—). An alternative embodiment features a variant of Protein A in which the C-terminal residue is cysteine.
    Type: Grant
    Filed: June 9, 1997
    Date of Patent: June 4, 2002
    Assignee: Pharmacia Biotech AB
    Inventor: Ingemar Johansson
  • Patent number: 6387974
    Abstract: Macroporous polymers having selected porosity and permeability characteristics that provide rigid polymer matrices suitable for use in medium and high pressure reversed phase liquid chromatography (RPC) are disclosed. A method for preparing the polymers using selected mixed porogens in selected proportions relative to the monomer phase is also disclosed. The polymers are especially useful as stationary phases in large scale chromatography columns without developing increased pressures during prolonged use, while maintaining good chromatographic performance for targeted biomolecules, such as insulin.
    Type: Grant
    Filed: August 7, 2001
    Date of Patent: May 14, 2002
    Assignee: Rohm and Haas Company
    Inventors: Karl Chaplin Deissler, Marlin Kenneth Kinzey, John Joseph Maikner, Robert E. Rosen
  • Patent number: 6388054
    Abstract: The present invention provides compounds useful to inhibit tumor growth and to induce apoptosis. In general, the anti-cancer agents (ACA) are described by the formula: [ACA]n-X  [Formula I] wherein X is a linker group having 2-5 functional groups or is absent, n=1, and ACA is selected from the group consisting of Formula II, Formula III, Formula IV, Formula V, and Formula VI, as described herein. Other compounds described herein are defined by the Formula VII, as described herein.
    Type: Grant
    Filed: August 19, 1999
    Date of Patent: May 14, 2002
    Inventors: John M. Stewart, Daniel C. F. Chan, Lajos Gera, Eunice York, Paul Bunn