Carrier Is Carbohydrate Patents (Class 435/178)
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Patent number: 6787358Abstract: The present invention relates to a method of forming a pattern of cells on a surface, the surface being prepatterned in having a pattern of cell-growth-promoting molecules and/or cell-growth inhibiting molecules attached thereon. The invention also relates to patterns of cells, artificial tissues and to a use thereof.Type: GrantFiled: October 19, 2001Date of Patent: September 7, 2004Assignees: Sony International (Europe) GmbH, Max-Planck-Gesellschaft Zur Forderung der Wissenschaften E.V.Inventors: Gabriele Nelles, Akio Yasuda, Wolfgang Knoll, Andreas Offenhäusser, Chi-Kong Yeung, Lars Lauer
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Patent number: 6783964Abstract: Methods of treating and forming biocompatible microcapsules that contain living cells are provided, to improve the function of the microcapsules. In particular, methods of treating islet cells or microcapsules containing islet cells are provided. Culture of isolated islet cells prior to encapsulation, culture of encapsulated cells, and cryopreservation of islet cells prior to encapsulation, are described. Methods for harvesting viable islets that incorporates an anti-oxidant in the digestion medium are also disclosed.Type: GrantFiled: January 23, 2002Date of Patent: August 31, 2004Assignee: Duke UniversityInventor: Emmanuel C. Opara
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Patent number: 6783962Abstract: 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: GrantFiled: November 20, 2001Date of Patent: August 31, 2004Assignee: UpFront ChromatographyInventors: Morten Aae Olander, Allan Otto Fog Lihme, Timothy John Hobley, Marcos Simon, Irini Theodossiou, Owen Robert Tyrynis Thomas
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Patent number: 6780643Abstract: Compositions of matter are described which contain restricted cancer cells. When so restricted, the cells produce an unexpectedly high amount of material which suppresses cancer cell proliferation. The phenomenon crosses cancer type and species lines. Processes for making these compositions, and their use, are also described.Type: GrantFiled: December 12, 2000Date of Patent: August 24, 2004Assignee: The Rogosin InstituteInventors: Shirin Asina, Kanti Jain, Albert L. Rubin, Barry Smith, Kurt Stenzel
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Patent number: 6761887Abstract: Disclosed are a composition of chemically defined components which support in vitro and in vivo chondrogenesis of mesenchymal stem cells, a method for in vitro and in vivo chondrogenic induction of such stem cells, and a method of forming human chondrocytes in vitro and in vivo from such stem cells.Type: GrantFiled: June 21, 2001Date of Patent: July 13, 2004Assignee: Osiris Therapeutics, Inc.Inventors: Karl Kavalkovich, Raymond Boynton, Mary Murphy, Frank Barry
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Patent number: 6753179Abstract: The present invention provides a method of biological treatment for purifying an environmental pollutant utilizing microorganisms, wherein the pollutant is efficiently concentrated to a high concentration but exerts substantially no effect on the biological activity of the microorganisms used to biodegrade the pollutant, so that the pollutant are purified (assimilated or degraded) effectively. The present invention also provides a microbial treatment agent useful for the purification treatment of an environmental pollutant. Specifically stated, the method for purification treatment of the present invention can be carried out by making an environmental pollutant and microorganisms to coexist with each other as incorporated in a microorganism-produced polymer. The microbial treatment agent of the present invention comprises microorganisms incorporated in a microorganism-produced polymer.Type: GrantFiled: December 8, 2000Date of Patent: June 22, 2004Assignee: Allmighty Co., Ltd.Inventor: Akihito Tsuchiya
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Patent number: 6749865Abstract: 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: GrantFiled: February 15, 2001Date of Patent: June 15, 2004Assignee: Genzyme CorporationInventors: Pericles Calias, Robert J. Miller
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Patent number: 6730298Abstract: Slowly polymerizing polysaccharide hydrogels have been demonstrated to be useful as a means of delivering large numbers of isolated cells via injection. The gels promote engraftment and provide three dimensional templates for new cell growth. The resulting tissue is similar in composition and histology to naturally occurring tissue. This method can be used for a variety of reconstructive procedures, including custom molding of cell implants to reconstruct three dimensional tissue defects, as well as implantation of tissues generally.Type: GrantFiled: January 20, 1998Date of Patent: May 4, 2004Assignees: Massachusetts Institute of Technology, Children's Medical Center CorporationInventors: Linda Griffith-Cima, Anthony Atala, Charles A. Vacanti, Keith T. Paige
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Patent number: 6730314Abstract: A process is provided for the production of a human cartilage implant from chondrocytes cultured in vitro, which come as close as possible to the original with respect to their biochemical composition and biomechanical properties. Up to 20% vol. of human serum is used as medium addition in the process. The chondrocytes can be kept in monolayer culture until the 12th passage in order firstly to be re-differentiated, incubated under a reduced oxygen partial pressure, and subsequently stimulated to form a three-dimensional cartilage tissue due to aggregation under an oxygen partial pressure of 21%. In an embodiment, chondrocytes in alginate beads are cultured in a nutrient solution, which may contain human serum and one or more chondrogenic growth factors, under an oxygen partial pressure of less than 20 volume %, isolated from the alginate beads by a treatment with a chelating agent, aggregated by centrifugation and cultured under an oxygen partial pressure of: −21 volume %.Type: GrantFiled: August 29, 2001Date of Patent: May 4, 2004Assignee: Merck Patent GesellschaftInventors: Brigitte Jeschke, Jörg Meyer, Peter Adamietz, Norbert Meenen, Christiane Göpfert
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Patent number: 6726934Abstract: The present invention provides a method of making particles useful in drug delivery, comprising the steps of: contacting polyanionic polymers with cations in a stirred reactor so that polyanions and the cations react to form particles.Type: GrantFiled: October 9, 1998Date of Patent: April 27, 2004Assignee: Vanderbilt UniversityInventor: Ales Prokop
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Patent number: 6723539Abstract: An adsorbent medium is prepared comprising particles of a sponge material made of cellulose or agarose carrying functional groups such as diethylaminoethane groups. The particles may be obtained by chopping a larger block of the sponge material. The medium preferably has a water retention value of greater than 6 ml/g and a particle size of 0.5 to 10 mm, and the sponge material may be cross-linked. The adsorbent medium is especially useful for purifying DNA in an aqueous sample.Type: GrantFiled: August 13, 2001Date of Patent: April 20, 2004Assignee: BioProcessing, Ltd.Inventors: Katherine Louise Angus, David Alan Hutton, Robert John Noel, Linda Taylor
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Patent number: 6709762Abstract: The invention provides a sewage purification assist toilet paper that carries pineapple enzyme and at least one powdery additive selected from slag, porous ore, and activated carbon. The pineapple enzyme and additive decompose salinity and chlorides contained in toilet sewage which otherwise would inhibit the growth of microorganisms used in the biological treatment of sewage taking place not only in individual septic tanks but also in public sewage systems.Type: GrantFiled: August 2, 2001Date of Patent: March 23, 2004Inventor: Shizuo Uyama
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Patent number: 6699465Abstract: A chemo-physiological structure and method for forming the chemo-physiological structure. In a first embodiment, a cell of an animal is provided. The cell has a membrane surface and a viral receptor coupled to the membrane surface. A linker molecule having a covalently attached polymer is covalently bonded to the membrane surface, the viral receptor, or both. The polymer prevents an extracellular virus from bonding to the viral receptor. In a second embodiment, a linker molecule having a covalently attached polymer is covalently bonded to a capsid of a virus, which prevents the virus from bonding to a viral receptor of an adjacent or nearby animal cell.Type: GrantFiled: May 18, 2001Date of Patent: March 2, 2004Assignee: Albany Medical CollegeInventor: Mark D. Scott
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Patent number: 6699470Abstract: A cell delivery device is prepared comprising a controllable degradable gel phase, meshed within a polymer substrate for use in tissue-engineering. The gel phase comprises a degradable, natural or synthetic polymer, and includes a suspension of living cells. The polymer substrate comprises a biocompatible, degradable polymer, and may be synthetic or natural. Degradation of the gel phase may be controlled by enzyme activity or adjustment of gel phase physical properties. In one embodiment, the gel phase contains an enzyme and/or enzyme inhibitor to control degradation of the gel phase. The device is useful in tissue replacement and repair, and more particularly, in the repair of cartilage tissue.Type: GrantFiled: October 10, 2000Date of Patent: March 2, 2004Assignee: Massachusetts Institute of TechnologyInventors: Guillermo A. Ameer, Robert S. Langer, Jr.
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Patent number: 6689588Abstract: Immobilized garlic alliinase wherein the alliinase is chemically, physically or biologically immobilized, is useful in a method for continuous production of allicin. The method comprises adding a solution of alliin as substrate to a column containing the immobilized garlic alliinase and collecting pure allicin in the effluent. The pure allicin is intended for use as food additive or for the preparation of pharmaceutical compositions for the treatment of viral, bacterial, fungal and parasitic infections, high levels of cholesterol and blood lipids, high blood pressure and thrombosis.Type: GrantFiled: September 12, 2000Date of Patent: February 10, 2004Assignee: Yeda Research and Development Co. Ltd.Inventors: David Mirelman, Meir Wilchek, Talia Miron, Aharon Rabinkov, Hephzibah Sivaraman
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Patent number: 6686208Abstract: The invention relates to devices and methods for carrying out quantitative fluorescence immunoassays using evanescent field excitation. Light from at least one light source is directed onto the boundary between two media which have differing refractive indices. The light source emits practically monochromatic light with a wavelength suitable for exciting a marking substance. The light is directed onto a boundary surface disposed between an optically transparent base plate, the refractive index of which is greater than that of the material above the boundary surface, and a receiving region for the sample. The receiving region is covered with a covering plate on the side disposed opposite the base plate, there being arranged between the base plate and covering plate at least one functional layer. A detector for detecting the fluorescent light is disposed on the same side of the base plate as the light source.Type: GrantFiled: August 6, 2002Date of Patent: February 3, 2004Assignee: Institut fur Chemo- und Biosensorik Munster e.V.Inventors: Markus Meusel, Dieter Trau, Andreas Katerkamp
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Patent number: 6680184Abstract: A temperature-stable droplet is provided containing a temperature-stable hydrocolloid membrane. The hydrocolloid membrane encapsulates a liquid that contains at least one enzyme, a cell, a biological agent, a pharmaceutical agent, an immunological agent, or mixtures thereof, and at least one of a locust bean gum, a natural thickening agent, a guar, polyvinylpyrrolidone, Konjac mannan, methylcellulose, hydroxymethylcellulose, calcium gluconate, glucomannan, or mixtures thereof. Preferably, the hydrocolloid membrane comprises at least one of methoxy pectin, Konjac mannan, sodium alginate, or mixtures thereof, and at least one of a locust bean gum, methylcellulose, hydroxymethylcellulose, glucomannan, or mixtures thereof. The hydrocolloid membrane encapsulating the liquid is a thickness capable of holding the liquid without bursting through a temperature range of about −20° C. to about 90° C.Type: GrantFiled: September 29, 1999Date of Patent: January 20, 2004Assignee: Yissum Research & Development Co. of Hebrew UniversityInventor: Amos Nussinovitch
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Patent number: 6673244Abstract: A magnetic sludge which is suitable for use in waste water treatment, is easy to prepare, contains microbes and interacts with a magnetic field; and a method for treating waste water with improved efficiency comprising employing a biological membrane which uses the magnetic sludge and hence is easy to control its movement.Type: GrantFiled: October 31, 2001Date of Patent: January 6, 2004Assignee: Japan Science and Technology CorporationInventors: Takaaki Maekawa, Mitsuaki Kuroshima
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Patent number: 6656876Abstract: A storage stable composition comprising a carrier usable for the immobilization of compounds containing an amine group, for instance biomolecules and/or affinity ligands. The carrier has been activated to exhibit a squaric acid derivative linked to the carrier and is placed in contact with an aqueous medium. A kit comprising the storage stable composition is also disclosed.Type: GrantFiled: May 22, 2001Date of Patent: December 2, 2003Assignee: Amersham Biosciences ABInventor: Per-Mikael Åberg
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System and method for encapsulating biological material by applying electrostatic charge to capsules
Patent number: 6649384Abstract: A method and system for the effective and consistent encapsulation of viable (i.e., living or physiologically active) biological material (preferably, pancreatic islets also known as islets of Langerhans) with a polymeric material (preferably, a biocompatible semipermeable alginate) to form a gelled capsule, which preferably can be transplanted into genetically dissimilar hosts. The method includes an electrostatic mixing process for producing encapsulated cell clusters with at least two polymeric coatings, and the system includes an improved spinning disk atomizer. In an embodiment, biological material is encapsulated in a first alginate layer, the resultant capsules are suspended in a liquid carrier medium such as a saline solution, an electrostatic charge is applied to the carrier medium which is then introduced into an alginate solution, and the resultant suspension is atomized and gelled to form a second alginate layer.Type: GrantFiled: July 5, 2001Date of Patent: November 18, 2003Assignee: Islet Technology, Inc.Inventors: Stephen E. Walsh, Monte R. Canfield, Nancy J. Drake -
Three-dimensional cell culture material having sugar polymer containing cell recognition sugar chain
Patent number: 6642050Abstract: A cell culture material comprising a sugar containing polymer in which at least one kind of sugar chain is bonded as a side chain via a spacer molecule is made into a three-dimensional shape whereupon a three-dimensional cell material is prepared. With regard to the sugar containing polymer, a sugar containing polymer having a carboxyl group such as alginic acid, hyaluronic acid, pectic acid or a derivative thereof is preferably used. Sugar chain having a specific recognition to a cell is bonded as a side chain and, therefore, when the cell is incubated using the cell culture material, it is possible to maintain and improve the proliferation, morphology and function of the cells and to retain the cell form in a form of near that in vivo due to a specific interaction between the cell and the sugar chain.Type: GrantFiled: March 16, 2001Date of Patent: November 4, 2003Assignee: Amcite Research, Ltd.Inventors: Mitsuaki Goto, Toshihiro Akaike, Jun Yang -
Patent number: 6632446Abstract: 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: GrantFiled: October 23, 2000Date of Patent: October 14, 2003Assignee: The Board of Regents, University of Texas SystemInventors: Jeffrey A. Hubbell, Chandrashekhar P. Pathak, Amarpreet S. Sawhney, Neil P. Desai, Jennifer L. Hill, Syed F. A. Hossainy
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Patent number: 6620611Abstract: A slow-release solid chemical composition for environmental bioremediation is provided. The composition comprises a source of soluble organic substrates which include sugars, soluble organic polymers and mixtures of them in an amount of 7% to 90%, insoluble organic substrates an amount of 10% to 70%, complex inorganic phosphates in an amount of 0.5% to 7% and soluble organic salts in an amount of 2% to 70%. The insoluble organic substrates include fibrous plant materials, starches, cellulosic materials and mixtures of these substrates. The complex inorganic phosphates include ringed metaphosphates, linear polyphosphates and mixtures. The organic salts include lactates, formates, acetates, citrates, etc. Also the composition further comprises microorganisms which include Bacillus spp., Rhizobium spp., Bradyrhibzobium spp., Fibrobacter spp., Clostridium spp., Pseudomonas. spp., Geobacter spp., Arthrobacter spp., Nocardia, spp., aspergillus spp., Trichoderma spp., Candida spp., Yarrowia spp.Type: GrantFiled: January 6, 2001Date of Patent: September 16, 2003Assignee: Geovation Technologies, Inc.Inventor: Eric Christian Hince
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Patent number: 6616946Abstract: Polymeric hollow particles for delivery of an agent are provided that change permeability in response to a change in an external stimulus such as pH, temperature, light, ionic strength, electric field, magnetic field and/or solvent composition. The particles can have a shell formed of an amphiphilic triblock ABA or BAB copolymer, where A is a hydrophilic block and B is a hydrophobic block. Low permeability particles with a reversibly permeable shell expand and increase permeability in response to a stimulus so that an active agent such as a therapeutic, prophylactic or diagnostic agent can be introduced. Removing the stimulus allows the particles to return to a low permeability state to form particles loaded with the active agent. Surfaces of the particles can be modified with specific ligands that allow the particles to be directed to a specific target via molecular recognition.Type: GrantFiled: November 15, 2000Date of Patent: September 9, 2003Assignee: BioCure, Inc.Inventors: Wolfgang Meier, Marc Sauer
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Patent number: 6610668Abstract: The present invention relates to a purified, easily produced poly-&bgr;-1→4-N-acetylglucosamine (p-GlcNAc) polysaccharide species. The p-GlcNAc of the invention is a polymer of high molecular weight whose constituent monosaccharide sugars are attached in a &bgr;-1→4 conformation, and which is free of proteins, and substantially free of single amino acids, and other organic and inorganic contaminants. In addition, derivatives and reformulations of p-GlcNAc are described. The present invention further relates to methods for the purification of the p-GlcNAc of the invention from microalgae, preferably diatom, starting sources. Still further, the invention relates to methods for the derivatization and reformulation of the p-GlcNAc. Additionally, the present invention relates to the uses of pure p-GlcNAc, its derivatives, and/or its reformulations.Type: GrantFiled: May 29, 2001Date of Patent: August 26, 2003Assignee: Marine Polymers TechnologiesInventors: John N. Vournakis, Sergio Finkielsztein, Ernest R. Pariser, Mike Helton
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Patent number: 6602716Abstract: A method and device for fluorimetric determination of a biological, chemical or physical parameter of a sample utilize at least two different luminescent materials, the first of which is sensitive to the parameter, at least with respect to luminescence intensity, and the second of which is insensitive to the parameter, at least with respect to luminescence intensity and decay time. The luminescent materials have different decay times. The time- or phase behaviour of the resulting luminescence response is used to form a reference value for determination of a parameter.Type: GrantFiled: April 10, 2000Date of Patent: August 5, 2003Assignee: PreSens Precision Sensing GmbHInventor: Ingo Klimant
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Patent number: 6602691Abstract: The invention relates to the production of mannitol by bioconversion with the aid of immobilized micro-organisms as well as to the use of the mannitol and by-products formed in the conversion process. In said process a solution containing a substrate convertible into mannitol is fed into contact with solid carrier particles containing viable mannitol-forming microorganism cells immobilized in and/or on said particles. The solution is reconditioned between successive conversion steps in order to provide conversion of a major portion of said substrate into mannitol.Type: GrantFiled: January 9, 2001Date of Patent: August 5, 2003Assignee: Xyrofin OyInventors: Heikki Ojamo, Hannu Koivikko, Heikki Heikkilä
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Publication number: 20030143281Abstract: Compositions of matter are described which contain restricted cancer cells. When so restricted, the cells produce an unexpectedly high amount of material which suppresses cancer cell proliferation. The phenomenon crosses cancer type and species lines. Processes for making these compositions, and their use, are also described.Type: ApplicationFiled: January 3, 2003Publication date: July 31, 2003Inventors: Shirin Asina, Kanti Jain, Albert L. Rubin, Barry Smith, Kurt Stenzel
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Patent number: 6596310Abstract: A method is provided for encapsulating sperm in a particle wherein the particle provides for the timed release of the sperm. In particular, the method uses a gel forming polymer to form the particle and a medium for maintaining most of the sperm in a non-capacitated stage while it is encapsulated. Further provided is a method for artificial insemination using the encapsulated sperm wherein the sperm is naturally or artificially capacitated after the artificial insemination. In an embodiment, capsules containing a core of sperm in a semen extender are formed as a mixture having membranes of different thicknesses to provide varying time of sperm release. In another embodiment, the sperm and extender are dispersed throughout solid beads that vary in chemical property and diameter to provide varying time of sperm release. The extender may be free of glucose, xanthine oxidase and H2O2, and contain fructose, fructose-6-phosphate, pyruvate, lactate or mixtures thereof as a carbohydrate source.Type: GrantFiled: August 23, 2000Date of Patent: July 22, 2003Assignees: Board of Trustees operating Michigan State University, University of MichiganInventors: Kuo-Chuan Karen Chou, Henry Y. Wang
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Patent number: 6596532Abstract: A device and method are provided for isolating and culturing microorganisms from a bulk fluid sample. The device comprises a container having therein a polymeric immobilization layer having interstitial spaces between polymer chains such as a gel matrix. The interstitial spaces are of an average size less than an average size of microorganisms to be separated from the sample and cultured. A bulk fluid sample is applied to the immobilization layer where fluid is absorbed by the layer and microorganisms remain on the surface of the layer. After culturing, microorganism colonies are readily accessible on the surface of the layer for harvest and testing. The immobilization layer may contain one or more of nutrients for microorganism growth, lytic agents, lytic enzymes, antibiotics, antibiotic neutralizers, indicators, detergents and selective agents. An adjacent support layer may be above and/or below the immobilization layer.Type: GrantFiled: February 11, 2000Date of Patent: July 22, 2003Assignee: bioMérieux, Inc.Inventors: Jones M. Hyman, Paul M. Matsumura, Scott R. Jeffrey, Martin J. Maresch, Thurman C. Thorpe
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Patent number: 6592886Abstract: A stable cross-linked alginate gel such as in the form of alginate gel beads encapsulating transplant materials is produced by binding surplus multivalent cations remaining after cross-linking alginate with the cations. A cross-linked alginate gel containing the surplus cations is contacted with a solution of multivalent anions such as sodium sulfate solution to bind the surplus cations. Preferably, a dehydration preventing agent such as protein, bone powder or implant substances is present during cross-linking. A hydrophobic substance such as a perfluoro hydrocarbon or an emulsion may be present during cross-linking to fill spaces between alginate chains. Alginate gel beads produced by the process have long term stability after transplanting.Type: GrantFiled: January 27, 2000Date of Patent: July 15, 2003Assignee: CellMed AGInventor: Ulrich Zimmermann
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Publication number: 20030119157Abstract: The present invention relates to macroporous chitosan beads having 5-200 &mgr;m in size of relatively large and uniform pores that are distributed from surface to core region, and a preparation method thereof compring the following steps; by dropping chitosan solution, aqueous chitosan solution or their mixture into the low-temperature of organic solvent or liquid nitrogen; and by regulating pore size by phase separation method via temperature difference.Type: ApplicationFiled: June 17, 2002Publication date: June 26, 2003Inventors: Seo Young Jeong, Eunhee Bae, Ick Chan Kwon, Kuiwon Choi
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Publication number: 20030096218Abstract: A polymer product useful for adsorbing small molecular size solutes in the presence of large molecular size solutes comprises a matrix polymer, an affinity ligand, and a shielding ligand. The affinity ligand forms complexes with small molecular size solutes, while the shielding ligand prevents large molecular size solutes from forming complexes with the affinity ligand. The matrix polymer, affinity ligand, and shielding ligand are covalently bonded together. The affinity ligand and shielding ligand may both be independently bonded to the matrix polymer, or the affinity ligand may be bonded to the matrix polymer, and the shielding ligand bonded to the affinity ligand.Type: ApplicationFiled: May 7, 2002Publication date: May 22, 2003Applicant: Arizona Bd of Regents/Behalf of Univ. of ArizonaInventors: Roberto Guzman, Jerker Porath
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Patent number: 6558665Abstract: Particles such as islet cells are encapsulated by a method that forms a coating of uniform thickness that conforms to the size and shape of the particles. Two substantially immiscible liquids of different densities are provided in a container as upper and lower liquids such that an interface exists between the liquids. The upper liquid is less dense and has a greater viscosity than the lower liquid which is a coating liquid containing particles to be encapsulated. A tube is positioned in the upper liquid such that an orifice of the tube is above the interface. A pump connected to the tube sucks liquid through the tube at a rate sufficient to form a spout containing substantially the lower liquid extending between the interface and the tube orifice. The spout has maximum diameter at the interface and decreases in diameter as the spout approaches the tube orifice.Type: GrantFiled: May 18, 2000Date of Patent: May 6, 2003Assignee: Arch Development CorporationInventors: Itai Cohen, Sidney Nagel, Horacio Rilo, Milan Mrksich
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Patent number: 6555391Abstract: This invention relates methods for conditioning affinity chromatography resins to decrease leaching of the ligand during purification. The methods involve incubating the resin in a buffered solution of a hydroxyalkylamine compound (e.g., ethanolamine) prior to use of the resin for an affinity purification. The treatment removes unstably bound ligand from the resin.Type: GrantFiled: August 15, 2000Date of Patent: April 29, 2003Assignee: Baxter International, Inc.Inventors: Susan L. Bernhard, Robert Toso, Van Taiariol
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Patent number: 6541606Abstract: 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: GrantFiled: August 10, 1999Date of Patent: April 1, 2003Assignee: Altus Biologics Inc.Inventors: Alexey L. Margolin, Nazar K. Khalaf, Nancy L. St. Clair, Scott L. Rakestraw, Bhami C. Shenoy
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Publication number: 20030049811Abstract: A process for the preparation of an enzyme-containing granulate is disclosed where an aqueous enzyme-containing liquid is mixed with an edible carbohydrate-based solid carrier, such as starch, mechanically processed into granules, and subsequently dried. This enzyme granulate is suitable for the manufacture of animal feed compositions by mixing feed ingredients with the granulate, treating with steam and pelleting. The compositions optimally show improved enzyme stability during the pelleting process.Type: ApplicationFiled: October 25, 2002Publication date: March 13, 2003Inventors: Rudolph Carolus Maria Barendse, Gabriel Marinus Henricus Meesters, Hans-Peter Harz
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Patent number: 6521431Abstract: 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: GrantFiled: June 22, 1999Date of Patent: February 18, 2003Assignee: Access Pharmaceuticals, Inc.Inventors: Patrick F. Kiser, Allen A. Thomas
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Patent number: 6511798Abstract: Cell based screens for studying drug transport are described and improved methods for the preparation of cell monolayers for use in such screens are disclosed.Type: GrantFiled: March 16, 1999Date of Patent: January 28, 2003Assignee: Zeneca LimitedInventor: Charles Michael Shaw
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Publication number: 20030003441Abstract: A portable pathogen detection system that accomplishes on-site multiplex detection of targets in biological samples. The system includes: microbead specific reagents, incubation/mixing chambers, a disposable microbead capture substrate, and an optical measurement and decoding arrangement. The basis of this system is a highly flexible Liquid Array that utilizes optically encoded microbeads as the templates for biological assays. Target biological samples are optically labeled and captured on the microbeads, which are in turn captured on an ordered array or disordered array disposable capture substrate and then optically read.Type: ApplicationFiled: June 12, 2001Publication date: January 2, 2003Applicant: The Regents of the University of CaliforniaInventors: Billy W. Colston, Matthew Everett, Fred P. Milanovich, Steve B. Brown, Kodumudi Venkateswaran, Jonathan N. Simon
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Patent number: 6500426Abstract: Enzyme-containing granules for manufacturing animal feed compositions are prepared using a carrier containing at least about 15% (w/w) carbohydrate such as starch and less than 5% (w/w) protein. A mixture is formed containing an enzyme, the carrier and water, with or without prior kneading to improve plasticity, the mixture is mechanically processed such as by extrusion with a basket or dome extruder while not allowing the temperature of the mixture to rise above about 40° C., and drying the resultant enzyme-containing granules. The granules may be spheronised prior to drying, and drying may be in a fluid bed agglomerator. The water and enzyme may be provided as an enzyme-containing aqueous liquid such as an enzyme-containing filtrate from a fermentation process. Enzymes include phytase, endo-xylanase and &bgr;-glucanase. Other components that may be in the granules include divalent cations, cellulose, polyvinyl alcohol and an edible oil.Type: GrantFiled: June 4, 1998Date of Patent: December 31, 2002Inventors: Rudolf Carolus Maria Barendse, Gabriel Marinus Henricus Meesters, Hans-Peter Harz
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Patent number: 6500933Abstract: 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: GrantFiled: March 3, 2000Date of Patent: December 31, 2002Assignee: Altus Biologics Inc.Inventors: Alexey L. Margolin, Chandrika P. Govardhan, Kalevi J. Visuri, Sinikka S. Uotila
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Publication number: 20020192775Abstract: Granules that include a protein core are described. The protein core includes a protein matrix which includes a protein mixed together with a starch. The protein matrix can be layered over a seed particle or the protein core can be homogeneous. The protein can be an enzyme or a therapeutic protein.Type: ApplicationFiled: June 25, 2002Publication date: December 19, 2002Inventors: Nathaniel T. Becker, Thomas S. Green
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Patent number: 6495136Abstract: Protease conjugates such as subtilisin conjugates are provided comprising a protease moiety and one or more addition moieties wherein the protease moiety has a modified amino acid sequence of a parent amino acid sequence. The parent amino acid sequence comprises a first epitope region, a second epitope region and a third epitope region, and the modified amino acid sequence comprises a substitution by a substituting amino acid at one or more positions in one or more of the epitope regions. When a substitution occurs in the first epitope region, the substitution occurs at one or more positions corresponding to positions 70-84 of subtilisin BPN′. When a substitution occurs in the second epitope region, the substitution occurs at one or more positions corresponding to positions 103-126 of subtilisin BPN′. When a substitution occurs in the third epitope region, the substitution occurs at one or more positions corresponding to positions 217-252 of subtilisin BPN′.Type: GrantFiled: June 2, 1998Date of Patent: December 17, 2002Assignee: The Procter & Gamble CompanyInventors: David John Weisgerber, Donn Nelton Rubingh, Paul Elliott Correa
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Patent number: 6465001Abstract: 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: GrantFiled: March 3, 1998Date of Patent: October 15, 2002Assignee: Board of Regents, The University of Texas SystemsInventors: Jeffrey A. Hubbell, Chandrashekhar P. Pathak, Amarpreet Sawhney, Neil Desai, Syed Hossainy, Jennifer L. Hill-West
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Patent number: 6465226Abstract: Biologically active substances such as cells or tissue are microencapsulated by methods that provide a high proportion of microcapsules containing a core of the biologically active substance as compared to microcapsules not containing the biologically active substance. Microcapsules are obtained having a maximum diameter of 300 micrometers and a high concentration of biologically active substance. A solution of encapsulating material such as alginate containing dispersed biologically active substance is passed through an inner channel of a two-channel spray nozzle to form droplets containing a core of the biologically active substance. Air flow from an outer channel of the nozzle causes the droplets to break off from the nozzle. Conditions of air flow and flow rate of solution are selected to obtain droplets having a volume of 1.5 to 4 times the volume of the biologically active substance that forms the core.Type: GrantFiled: October 19, 1998Date of Patent: October 15, 2002Inventor: Ulrich Zimmermann
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Patent number: 6444261Abstract: 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: GrantFiled: July 20, 1998Date of Patent: September 3, 2002Assignee: Abion Beteiligungs-und Verwaltungsgesellschaft mbHInventors: Dmitri Plaksine, Elena Gromakovskaia, Christoph Erhardt
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Publication number: 20020119539Abstract: Method for purifying bone-derived TGF-&bgr; proteins including an anion exchange process, a cation exchange process, and a reverse phase HPLC process, and optionally, a filtration process, a Heparin-Sepharose process, and/or a reverse phase HPLC desalting process. The filtration process preferably selects proteins having a nominal molecular weight between approximately 10 kilodaltons and approximately 100 kilodaltons. Preferably, the anion exchange process uses a strongly cationic resin having quaternary amine functional groups. Preferably, the cation exchange process uses a strongly anionic resin having sulfonic acid functional groups. The TGF-&bgr; proteins can be eluted from the reverse phase HPLC column with an acetonitrile solution in combination with aqueous trifluoracetic acid. The purification processes yield highly enriched TGF-&bgr;1, and TGF-&bgr;2 proteins.Type: ApplicationFiled: December 19, 2000Publication date: August 29, 2002Inventors: Louis Junker, Michael Lewis, Robert Nelson
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Patent number: 6433078Abstract: 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: GrantFiled: October 23, 2000Date of Patent: August 13, 2002Assignee: Polium Technologies, Inc.Inventors: Mikhail Y. Gololobov, Victor M. Ilyashenko
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Patent number: RE38027Abstract: Biological agents such as secretory cells are encapsulated in a hydrophilic gel made of agarose or collagen-agarose and gelatin sponge-agarose combinations. In a preferred embodiment, semi-solid beads are formed from a suspension containing collagen, agarose and secretory cells such as pancreatic islets, the collagen is polymerized to form solid, agarose-collagen beads and the solid beads are coated with agarose. Coating is preferably by rolling the solid beads in about 5-10% agarose, contacting the rolled beads with mineral oil and washing oil from the beads. Beads containing secretory cells can be transplanted into a mammal to treat a condition caused by impaired secretory cell function.Type: GrantFiled: June 30, 1999Date of Patent: March 11, 2003Assignee: The Rogosin InstituteInventors: Kanti Jain, Albert L. Rubin, Barry Smith