Enzyme Or Microbial Cell Is Entrapped Within The Carrier (e.g., Gel, Hollow Fibre) Patents (Class 435/182)
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Patent number: 6326178Abstract: Disclosed herein is a method for synthesizing a composite of a conductive macromolecule and a protein component. The method utilizes, as the protein component, a protein composite consisting of protein bonded to a macromolecular anion. The protein composite can serve as a dopant to improve an electrical conductivity of the conductive macromolecule and also to impart multifunctional properties to the conductive macromolecule.Type: GrantFiled: January 6, 2000Date of Patent: December 4, 2001Assignee: Kwangju Institute of Science and TechnologyInventors: Yon-Han Bae, Won-Jun Sung
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Patent number: 6315994Abstract: A cell culture medium and hydrogel matrix for long term storage and proliferation of cells is provided. The cell culture medium and hydrogel matrix include an effective amount of polar amino acids, the polar amino acids selected from the group consisting of arginine, lysine, histidine, glutamic acid, and aspartic acid. The cell culture medium comprises about 5 to about 150 mM of polar amino acids. The hydrogel matrix comprises about 3 to about 150 mM of polar amino acids. Arginine and glutamic acid are preferably supplemented in the cell culture medium. Arginine, lysine, and glutamic acid are preferably supplemented in the hydrogel matrix. A method of maintaining viability and functioning of a transplant is also provided. The method of maintaining viability of a transplant includes encapsulating the cells in a hydrogel matrix and injecting the encapsulated cells into the host organism.Type: GrantFiled: January 11, 2001Date of Patent: November 13, 2001Inventors: Anton-Lewis Usala, Richard Chris Klann
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Patent number: 6312942Abstract: Substances such as chemical substances and biological substances including animal, vegetable and microbial cells are encapsulated using a process and an apparatus wherein a coil through which alternating current flows causes a magnet to vibrate creating vibrations such as in the range of between 300 to 4000 Hz that are transmitted to an encapsulating fluid containing the substance to form small substantially spherical particles containing the substance. The apparatus includes a pulsation chamber containing a movable wall for receiving the encapsulating fluid containing the substance to be encapsulated. A nozzle is spaced downstream from the pulsation chamber for receiving the encapsulating fluid from the pulsation chamber. A permanent magnet is mounted on the movable wall, and a coil is spaced from the permanent magnet by an air gap and is located proximate to the permanent magnet.Type: GrantFiled: November 23, 1998Date of Patent: November 6, 2001Assignee: Inotech AGInventors: Raphael Plüss-Wenzinger, Fritz Widmer, Christoph Heinzen, Harry Brandenberger
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Patent number: 6303355Abstract: Cells, preferably isolated pancreatic islet cells, are treated with a compound or a combination of compounds selected from an antioxidant, an anti-cytokine, an anti-endotoxin and an antibiotic. The compound or combination of compounds is in a medium for culturing the cells before microencapsulation, in a medium for cryopreserving the cells by freezing followed by thawing and microencapsulation, in a medium for culturing the cells after microencapsulation, or in a medium for culturing the cells before microencapsulation and in a medium for culturing the cells after microencapsulation. In a preferred method, isolated pancreatic islet cells are cultured for about 12 to about 36 hours in a medium containing an antioxidant as the compound, cryopreserved by freezing in a medium containing the compound or combination of compounds, thawed and microencapsulated. The microcapsule contains a hydrogel core such gelled alginate and a semipermeable outer membrane such as formed with polylysine.Type: GrantFiled: March 22, 1999Date of Patent: October 16, 2001Assignee: Duke UniversityInventor: Emmanuel C. Opara
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Patent number: 6303151Abstract: A material for suppressing proliferation of cancer cells is produced by entrapping cancer cells in a selectively-permeable structure such as a bead, and culturing the entrapped cells in a culture medium. Entrapment restricts growth of the cancel cells during culturing and causes the cells to produce in the culture medium a material having a molecular weight of at least about 30 kd as measured by filtration that suppresses proliferation of cancer cells. The material is separated from the culture medium by filtering the medium through a filter that separates material having a molecular weight of at least about 30 kd from material having a molecular weight of less than 30 kd. The structure that entraps the cells may contain 10,000 to 500,000 cells. The material or the structure containing the entrapped cells that produce the material can be administered to a subject to suppress cancer cell proliferation.Type: GrantFiled: November 9, 1999Date of Patent: October 16, 2001Assignee: The Rogosin InstituteInventors: Shirin Asina, Kanti Jain, Albert L. Rubin, Barry Smith, Kurt Stenzel
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Patent number: 6303136Abstract: A device is prepared having cells or tissue attached to a non-degradable filamentous matrix surrounded by a semi-permeable membrane. The matrix is preferably formed of a plurality of monofilaments twisted into a yarn or woven into a mesh, and can be in the form of a cylinder. When implanting the device, the semi-permeable membrane is preferably immunolsolatory, and the cells or tissue may produce a biologically active molecule to provide therapy. To enhance cell or tissue adhesion, the matrix is coated with extracellular matrix molecules or treated to provide a surface charge. The device can be made by inserting the matrix into a capsule formed of the semi-permeable membrane, distributing the cells or tissue on the matrix through an opening of the capsule, and sealing the opening of the capsule.Type: GrantFiled: April 12, 1999Date of Patent: October 16, 2001Assignee: Neurotech S.A.Inventors: Rebecca Li, David Rein
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Patent number: 6299895Abstract: A method and device for delivering a biologically active molecule to the eye, either intraocularly or periocularly, and method and device for treating ophthalmic disorders in a patient suffering therefrom.Type: GrantFiled: April 27, 1999Date of Patent: October 9, 2001Assignee: Neurotech S.A.Inventors: Joseph P. Hammang, E. Edward Baetge, William G. Tsiarias, Peter D. Spear
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Patent number: 6297033Abstract: A system for nitrate removal from aquariums, both fresh water and marine aquariums, by means of permeable polymeric beads which contain a combination of fermentative and denitrifying bacteria and a carbon source. Preferred beads are beads made from sodium alginate or chitosan. The bacteria, in the presence of the carbon source, are able to reduce nitrate to nitrogen gas. Bacteria which are not harmful to fish are used. The porous beads used in the process are novel and part of the invention.Type: GrantFiled: March 5, 1998Date of Patent: October 2, 2001Assignee: Yissum Research Development Company of the Hebrew University of JerusalemInventors: Jaap Van Rijn, Amos Nussinovitch, Joseph Tal
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Patent number: 6290851Abstract: The present invention relates to magnetic carriers in which microorganisms requiring carriers for their growth in the step of treating wastewater have been immmobilized, a process for producing the carriers and a method of treating wastewater. The present invention provides microorganisms-immobilized carriers with a high amount of microorganisms immobilized for use in wastewater treatment, the movement of which is controllable in a treatment chamber by magnetic force. Further the present invention provides a process for producing said carriers easily and a method for treating wastewater efficiently.Type: GrantFiled: January 25, 2000Date of Patent: September 18, 2001Assignee: Japan Science and Technology CorporationInventors: Takaaki Maekawa, Mitsuaki Kuroshima
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Patent number: 6291582Abstract: A method of preparing a polymer-protein composite based upon placing a protein in solution in an organic phase via the ion-pairing of the protein with a surfactant. The polymer-protein composites are useful, for example, as highly active and stable catalysts, in for example, paints and coatings, as well as in medical application.Type: GrantFiled: November 10, 1999Date of Patent: September 18, 2001Assignee: Biotechnology Research & Development Corp.Inventors: Jonathan S. Dordick, Ping Wang, Maria Vladimir Sergeeva, Scott Joel Novick
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Patent number: 6287558Abstract: A device that includes a living cell or tissue and an agent that inhibits the ability of a host molecule to damage the cell or tissue. The device can be constructed in various forms including an implantable device, a composite microreactor and a double composite microreactor. The composite microreactor includes an internal particle that includes a living cell or tissue, an internal particle matrix that includes the living cell or tissue and an internal semipermeable coating enclosing the internal particle matrix, a gel super matrix in which the internal particle is embedded, and an agent that inhibits the ability of a host molecule to damage the cell or tissue. The double composite microreactor includes an internal particle, a particle that includes a particle matrix in which the internal particle is embedded, a super matrix in which the particle is embedded, and an agent that inhibits the ability of a host molecule to damage the living cell or tissue.Type: GrantFiled: August 1, 1997Date of Patent: September 11, 2001Assignee: BioHybrio Technologies LLCInventors: Robert P. Lanza, Dawn M. Ecker, John Ringeling, Joanne P. Marsh, William Chick
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Patent number: 6280983Abstract: Gel immobilized enzymes are prepared for use in carrying out reactions in hydrophobic solvents. The gel is formed from a gelatinizer such as gelatin or a polysaccharide such as agarose, agar, pectin, sodium alginate or carrageenan. The gel contains a ratio of amount of gelatinizer to amount of water such that the gel is capable of being mechanically divisible into dimensionally substantially stable fragments at a temperature which may reach a lower limit of the gelation temperature range of the gelatinizer. A preferred gel contains 30 to 50% gelatin, and is prepared by forming a mixture of water, enzyme and water-soluble gelatin, heating the mixture to dissolve the gelatin to form a solution, and cooling the solution until it forms a gel.Type: GrantFiled: February 12, 1999Date of Patent: August 28, 2001Inventors: Sune Backlund, Folke Eriksson, Gun Hedström, Stefan Karlsson
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Patent number: 6268191Abstract: Enzymes are immobilized for use in non-aqueous enzymatic reactions by dehydrating hydrocolloid gel beads having an average particle size of 5 to 150 microns and a network structure capable of swelling in aqueous media, immersing or suspending the dehyrated gel beads in an aqueous solution of enzyme where the beads swell and imbibe the enzyme solution, optionally dehydrating the resultant enzyme-containing gel beads and recovering the gel beads containing the enzyme. In a specific method, the hydrocolloid is carrageenan such a kappa carragennan, the enzyme is subtilisin Carlsberg, the aqueous enzyme solution contains 0.05% to 40 wt % enzyme and the amount of enzyme imbibed is 0.05 to 0.5 grams of enzyme per gram of dehydrated gel beads.Type: GrantFiled: September 14, 1999Date of Patent: July 31, 2001Inventors: Robert K. Prud'homme, Catherine-Ann Cukras, Henry A. Pfeffer
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Patent number: 6261585Abstract: An angiogenic material is provided which promotes extensive vascularization when implanted in animal tissue. The angiogenic material contains a biocompatible polymer and a vascularizing polymerizable compound capable of forming anions. The polymer may be a polyacrylate, and the polymerizable compound includes compounds having ionizable groups selected from sulfates, sulfonic acid groups and carboxyl groups. These compounds include acrylic acid, methacrylic acid, crotonic acid, itaconic acid, vinylsulfonic acid and vinylacetic acid. The angiogenic material is preferably used in microcapsule coatings and microspheres for implantation in animals. In microcapsules, the angiogenic material promotes better exchange of nutrients, waste products and cellular products between encapsulated cells and the circulatory system of the host animal.Type: GrantFiled: April 30, 1998Date of Patent: July 17, 2001Inventors: Michael Vivian Sefton, Julia E. Babensee, Michael H. May
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Patent number: 6258870Abstract: This invention provides novel methods for the formation of biocompatible membranes around biological materials using photopolymerization of water soluble molecules. The membranes can be used as a covering to encapsulate biological materials or biomedical devices, as a “glue” to cause more than one biological substance to adhere together, or as carriers for biologically active species. Several methods for forming these membranes are provided. Each of these methods utilizes a polymerization system containing water-soluble macromers, species which are at once polymers and macromolecules capable of further polymerization. The macromers are polymerized using a photoinitiator (such as a dye), optionally a cocatalyst, optionally an accelerator, and radiation in the form of visible or long wavelength UV light. The reaction occurs either by suspension polymerization or by interfacial polymerization.Type: GrantFiled: January 13, 1997Date of Patent: July 10, 2001Assignee: Board of Regents, The University of Texas SystemsInventors: Jeffrey A. Hubbell, Chandrashekhar P. Pathak, Amarpreet S. Sawhney, Neil P. Desai, Syed F. A. Hossainy
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Patent number: 6251646Abstract: A method for the stabilization of nitrilase activity of unimmobilized or immobilized microbial cells has been developed. The unimmobilized or immobilized microbial cells are stored in an aqueous solution containing from 0.100 M to the saturation concentration of an inorganic salt of bicarbonate or carbonate, including ammonium, sodium and potassium salts of bicarbonate or carbonate. Aqueous suspensions containing at least 100 mM bicarbonate or carbonate limit microbial contamination of the stored enzyme catalyst, as well as stabilize the desired nitrilase activity of the unimmobilized or immobilized cells. Microorganisms which are characterized by an nitrilase activity and are stabilized and preserved by this method include Acidovorax facilis 72-PF-15 (ATCC 55747), Acidovorax facilis 72-PF-17 (ATCC 55745), and Acidovorax facilis 72W (ATCC 55746).Type: GrantFiled: July 12, 1999Date of Patent: June 26, 2001Assignee: E. I. du Pont de Nemours and CompanyInventors: Robert Dicosimo, Arie Ben-Bassat, Robert D. Fallon
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Patent number: 6248321Abstract: Microparticles such as propagules of eukaryotic biocontrol agents are encapsulated in cellular-scale polymer capsules that have a diameter similar to normal eukaryotic cells in a range of about 10 &mgr;m to about 400 &mgr;m. The microparticles are encapsulated by adding a hydrophobic dispersion medium such as a mixture of chloroform and hexane or a mixture of corn oil and n-hexadecane having a specific gravity of about 1 and containing an emulsifier such as lecithin to an aqueous suspension of the microparticles and a polymer matrix precursor such as alginate, agitating vigorously to form a stable emulsion of microscopic globules containing a microparticle, and adding the emulsion to an aqueous solution containing a polymerizing agent such as calcium chloride to polymerize and precipitate the globules to form microparticles encapsulated in polymer matrix capsules that may be of a teardrop shape having a length of 40-200% longer than the diameter.Type: GrantFiled: January 14, 1999Date of Patent: June 19, 2001Assignee: Her Majesty the Queen in right of Canada, as represented by the Minister of Natural Resources, Canadian Forestry ServiceInventors: Richard Scott Winder, Jeffery Jerome Wheeler
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Patent number: 6242230Abstract: Oxalate-degrading enzymes and bacteria were encapsulated for both enteric and intraperitoneal administration. We have shown that via alginate microencapsulation of Oxalobacter formigenes, enzymatic activity was retained for several months. A new process was developed which strengthened the alginate microcapsules and their tolerance to citrate treatment. Much smaller (30-50 &mgr;m) alginate microcapsules were made for injection as means of implantation. For oral administration, multi-encapsulated microspheres of cellulose acetate phthalate in poly-2-vinylpyridine (pKa=3.5) were prepared to protect the enzymes from gastric juices.Type: GrantFiled: November 18, 1999Date of Patent: June 5, 2001Assignee: University of FloridaInventors: Chris Batich, Farid Vaghefi
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Patent number: 6242247Abstract: Cartilage tissue and implants comprising cartilage tissue are produced in vitro starting from cells having the ability to form an extracellular cartilage matrix. Such cells are brought into a cell space (1) and are left in this cell space for producing an extracellular cartilage matrix. The cells are brought into the cell space to have a cell density of ca. 5×107 to 109 cells per cm3 of cell space. The cell space (1) is at least partly separated from a culture medium space (2) surrounding the cell space by a semi-permeable wall (3) or by an open-pore wall acting as convection barrier. The open-pore wall can be designed as a plate (7) made of a bone substitute material and constituting the bottom of the cell space (1).Type: GrantFiled: March 4, 1999Date of Patent: June 5, 2001Assignee: Sulzer Orthopedics Ltd.Inventors: Franz Rieser, Werner Muller, Pedro Bittmann, Pierre Mainil-Varlet, Christoph P. Saager
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Patent number: 6242248Abstract: A bioreactor (10) has arranged within its internal chamber (14) a bundle of liquid-impermeable hollow tubes (16), which are used to freeze or vitrify a biologically active material seeded within the internal chamber. When the bioreactor is ready for use, the biologically active material may be thawed by perfusing the liquid-impermeable hollow tubes with a heated solution or heated vapor.Type: GrantFiled: February 8, 2000Date of Patent: June 5, 2001Assignee: Cedars-Sinai Medical CenterInventors: Jacek Rozga, Achilles A. Demetriou
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Patent number: 6232090Abstract: First and second reactants that give a signal when mixed in the presence of an analyte in a liquid sample, are separately contained in sol-gels that release the reactants in the presence of the liquid. For example, when the first and second reactants respectively comprise an oxidant and a reductant, and the reaction provides a detectable signal, the system can be used to detect the presence of contaminants in a water sample. The sol-gel may be obtained by reaction of water with, per part by volume thereof, at least 2 parts of a metal alkoxide, and drying the resultant gel.Type: GrantFiled: November 16, 1998Date of Patent: May 15, 2001Assignee: Randox Laboratories Ltd.Inventors: Stephen Peter Fitzgerald, John Victor Lamont, Robert Ivan McConnell
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Patent number: 6231881Abstract: A cell culture medium and hydrogel matrix for long term storage and proliferation of cells is provided. The cell culture medium and hydrogel matrix include an effective amount of polar amino acids, the polar amino acids selected from the group consisting of arginine, lysine, histidine, glutamic acid, and aspartic acid. The cell culture medium comprises about 5 to about 150 mM of polar amino acids. The hydrogel matrix comprises about 3 to about 150 mM of polar amino acids. Arginine and glutamic acid are preferably supplemented in the cell culture medium. Arginine, lysine, and glutamic acid are preferably supplemented in the hydrogel matrix. A method of maintaining viability and functioning of a transplant is also provided. The method of maintaining viability of a transplant includes encapsulating the cells in a hydrogel matrix and injecting the encapsulated cells into the host organism.Type: GrantFiled: July 10, 1998Date of Patent: May 15, 2001Inventors: Anton-Lewis Usala, Richard Chris Klann
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Patent number: 6225047Abstract: This is invention is directed to methods of identifying analytes that are differentially present between two samples. The methods involve determining retention data by desorption spectrometry for analytes in different samples using the same selectivity conditions, comparing the data, and identifying analytes that are differentially retained.Type: GrantFiled: June 19, 1998Date of Patent: May 1, 2001Assignee: Ciphergen Biosystems, Inc.Inventors: T. William Hutchens, Tai-Tung Yip
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Patent number: 6224912Abstract: A material for suppressing proliferation of cancer cells is produced by entrapping cancer cells in a selectively-permeable structure such as a bead, and culturing the entrapped cells in a culture medium. Entrapment restricts growth of the cancel cells during culturing and causes the cells to produce in the culture medium a material having a molecular weight of at least about 30 kd that suppresses proliferation of cancer cells. The material is separated from the culture medium by filtering the medium through a filter that separates material having a molecular weight of at least about 30 kd from material having a molecular weight of less than 30 kd. The structure that entraps the cells may contain 10,000 to 500,000 cells.Type: GrantFiled: November 9, 1998Date of Patent: May 1, 2001Assignee: The Rogo InstituteInventors: Shirin Asina, Kanti Jain, Albert L. Rubin, Barry Smith, Kurt Stenzel
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Patent number: 6221376Abstract: A novel neurotrophic factor referred to as glial cell line-derived neurotrophic factor (GDNF) has been identified. Genes encoding GDNF have been cloned and sequenced. Methods and devices are disclosed for the delivery of GDNF using either an implantable cell which expresses human GDNF or a biocompatible semipermeable membrane containing genetically engineered cells which express and secrete the neurotrophic factor.Type: GrantFiled: September 22, 1997Date of Patent: April 24, 2001Assignee: Amgen Inc.Inventors: Leu-Fen H. Lin, Franklin D. Collins, Daniel H. Doherty, Jack Lile, Susan Bektesh
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Patent number: 6218158Abstract: This invention relates to a process for enzymic oxidation of a fatty acid to produce an oxidation product in the presence of water and oxygen wherein the fatty acid, water and enzyme for the oxidation are substantially uniformly distributed throughout a porous bed of solid support material in the substantial absence of a continuous liquid phase, oxygen is passed through the porous bed and the oxidation product is recovered from the porous bed. The invention is of particular value for production of methyl ketones from saturated fatty acids.Type: GrantFiled: June 10, 1992Date of Patent: April 17, 2001Assignee: Bush Boake Allen LimitedInventors: Anthony Martin Humphrey, Bridget Ann Skill, Judith L. Kinderlerer
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Patent number: 6214262Abstract: A method of producing a three dimensional section of polymerized liquid. The method includes providing a molding apparatus which includes a mold having at least one side, at least one piece of porous material adjacent to the one side of the mold and at least one support layer adjacent to the piece of porous material. The molding apparatus is clamped together and a liquid is added between the frame and the porous material. The filled molding apparatus is placed in a bath of polymerizing agent until the liquid polymerizes to form a three dimensional section.Type: GrantFiled: March 12, 1999Date of Patent: April 10, 2001Assignee: Massachusetts Institute of TechnologyInventors: Paula Ragan, Alan Grodzinsky, Vicki Chin, Han Hwa Hung
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Patent number: 6214593Abstract: A suspension of animal cells is incubated with supports to adhere the cells to the supports. Preferably, the supports have pores that provide pore volume, and the cells are grown during incubation until most of the available pore volume is filled with cells. An encapsulating layer is then formed around the supported cells by exposing the cells on the supports to a reactive gas composed of a carrier gas such as sterile air saturated with an inorganic alkoxide followed by treatment with steam to hydrolyze residual alkoxide groups. The encapsulated cells are stored by immersion in culture media. The cells may be in the form of cell aggregates, and the supports can be sterilized. The supports and encapsulating layer can have pores of a size that permit free exchange nutrients and metabolic products, and excludes the cells from contacting antibodies or immune cells when implanted. The encapsulated cells can used in an extracorporeal device or implanted directly.Type: GrantFiled: November 27, 1998Date of Patent: April 10, 2001Assignee: Biosil A.G.Inventors: Giovanni Carturan, Maurizio Muraca, Renzo Dal Monte
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Patent number: 6183737Abstract: Isolated chondrocytes are propagated in the presence of a biological gel such as a fibrin gel to generate a cartilage matrix that firmly bonds together two adjacent cartilage pieces. A bonding composition containing the isolated chondrocytes mixed with the biological gel is applied to a surface of one (or both) of the cartilage pieces, and the surface is contacted with the other cartilage piece. In a different order of steps, the two cartilage pieces are held in apposition, and gaps at the interface are filled with the bonding composition. In another method, either or both of the cartilage pieces are first incubated with the isolated chondrocytes, the biological gel is then applied, and the cartilage pieces are held together. Alternatively, after incubating with isolated chondrocytes, the biological gel can be applied to fill gaps at the interface between cartilage pieces held in apposition.Type: GrantFiled: October 29, 1998Date of Patent: February 6, 2001Assignee: The General Hospital CorporationInventors: David J. Zaleske, Giuseppe Peretti, Enzo Caruso, Francesco Rossetti, Mark Randolph
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Patent number: 6180378Abstract: Immobilized bioactive protein compositions are prepared containing a bioactive protein such as an enzyme intercalated into galleries of a phyllosilicate, and a crosslinking compound crosslinking the phyllosilicate and the bioactive protein. The phyllosilicate may contain sodium or alkylammonium ions and be montmorillonite. The protein may be lipoxygenase, and crosslinking compounds include tetramethyl orthosilicate, tetraethoxy silicate, propyltrimethoxy silicate, polydimethylortho silicate and methyltrimethoxy silicate. The composition is prepared by delaminating a sodium-saturated phyllosilicate, mixing a bioactive protein with the delaminated phyllosilicate and crosslinking with a crosslinking compound. After crosslinking, the composition may be vacuum dried and ground.Type: GrantFiled: January 29, 1999Date of Patent: January 30, 2001Assignee: The United States of America as represented by the Secretary of AgricultureInventors: Siyuan Shen, An-Fei Hsu, Thomas A. Foglia, Shu-I Tu
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Patent number: 6180007Abstract: A permselective graft polymer is disclosed that is formed by converting into intermediate reactive sites a portion of the cyano groups of a backbone polymer containing —CH2—CH(—C≡N)— units, and grafting polyalkylene oxide polymer chains to the backbone polymer through the reactive sites. Either the backbone polymer of a polymer resin or a permselective polymer membrane can be grafted. When a resin is used, it is formed into a permselective polymer membrane using known methods. The resulting permselective membrane can be formed into hollow fibers or flat sheets for the encapsulation of living cells. The encapsulated cells are then implanted into a patient in need of the biologically active factors produced by the cells. The permselective graft polymer membrane exhibits good molecular diffusion with minimal protein adsorption.Type: GrantFiled: January 31, 1998Date of Patent: January 30, 2001Assignee: Neurotech, SAInventors: Frank Gentile, Molly Shoichet, Milton Harris
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Patent number: 6171813Abstract: A method is presented for catalyzing the conversion of substrate into product in an organic reaction solvent with an enzyme-surfactant ion pair. The enzyme-surfactant ion pair comprises the enzyme catalyzing the reaction and a surfactant capable of forming an ion pair with the enzyme. Water present in the organic solvent at a concentration of about 0.03% to about 2.5% is sufficient to enhance the rate of catalysis and stabilize the enzyme without substantially increasing the rate of hydrolysis when compared to the anhydrous enzyme.Type: GrantFiled: October 16, 1997Date of Patent: January 9, 2001Assignees: BioTechnology Research & Develop. Corp., The University of Iowa Research FoundationInventors: Jonathan S. Dordick, Vikram M. Paradkar, Maria V. Sergeeva
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Patent number: 6153416Abstract: Microorganisms or enzymes immobilized in beads are prepared using a combination of calcium alginate, polyethylene glycol (PEG) and polyethylene imide (PEI). An aqueous solution containing 1-14% by weight each of calcium alginate, PEG and PEI is combined with a concentrated solution of a microorganism or an enzyme to form a mixture. The mixture is combined with an aqueous solution of 4-8% w/v CaCl.sub.2 to form spherical beads that are allowed to remain in the solution for 3-4 hours. Thereafter, the beads are rinsed with water for 2-3 minutes, transferred to water in a mixer, and stirred with a magnet for 6-9 hours. The resultant beads containing the microorganism or enzyme can be used for removing inorganic nitrogen and organic carbon in waste water, or in processes for making biochemical products.Type: GrantFiled: January 20, 1999Date of Patent: November 28, 2000Inventor: Yu-Kang Yuan
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Patent number: 6150472Abstract: Polymers having multi-functional sites and a gel comprising a solvent swollen network of cross-linked polymer(s), of which at least one polymer comprises at least one multi-functional site. A multi-functional site is a sequence of more than one functional group. A multi-functional polymer is a polymer comprising one or more multi-functional sites and/or more than one functional group.Type: GrantFiled: September 14, 1998Date of Patent: November 21, 2000Assignee: Holland Biomaterials Group B.V.Inventor: Gerardus Henricus Maria Engbers
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Patent number: 6150505Abstract: The present invention provides fibrin microbeads that are biologically active and comprise extensively cross-linked fibrin(ogen) without using glutaraldehyde, and a method for preparing the fibrin microbeads. The present invention also provides a composition comprising cells bound to the fibrin microbeads, and methods for culturing and separating cells using the fibrin microbeads of the present invention. Finally, the present invention provides methods for transplanting cells and engineering tissue using the fibrin microbeads of the present invention.Type: GrantFiled: September 19, 1997Date of Patent: November 21, 2000Assignee: Hadasit Medical Research Services & Development Ltd.Inventors: Gerard Marx, Raphael Gorodetsky
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Patent number: 6146665Abstract: A hydrophilic or lipophilic drug is entrapped or microencapsulated in a polyhydroxyalkanoate homopolymer or copolymer. The homopolymer or copolymer is synthesized in an aqueous medium containing a dissolved hydrophilic drug by in vitro enzyme polymerization of a hydroxyalkanoate Coenzyme A monomer to form microporous granules entrapping the drug. The enzyme may be a polyhydroxyalkanoate synthase, and the monomer may be 3-hydroxybutyryl Coenzyme A or 3-hydroxyvalerate Coenzyme A. The monomer is produced by reaction of a carboxylic acid group of a hydroxyalkanoic acid with a thiol group of Coenzyme A. To microencapsulate a lipophilic drug, droplets of oil containing a lipophilic drug are formed dispersed in an aqueous medium such as in the form of an oil-in-water emulsion. The polyhydroxyalkanoate homopolymer or copolymer is formed in the aqueous medium by the enzyme polymerization to form microcapsules having a core of oil containing the drug. The granules or microcapsules containing the drug may be dried.Type: GrantFiled: September 9, 1998Date of Patent: November 14, 2000Assignee: McGill UniversityInventors: Robert H. Marchessault, Dusica Maysinger, Geoffrey Alan Ralph Nobes
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Patent number: 6140089Abstract: Encapsulated viable cells for implanting are prepared having cells dispersed in a particulate, essentially non cross-linked chitosan core matrix that is enclosed within a semipermeable membrane. The cells are entrapped between chitosan particles of the core matrix and there is essentially no interfacial cross-linking between the core matrix and the membrane. The core matrix provides a physical support for the cells such that the cells are evenly dispersed throughout the core matrix so as to allow their maintenance, growth, proliferation and differentiation. The encapsulated cells may be prepared by mixing viable cells with a solution of chitosan, encapsulating the resultant mixture in a thermoplastic semipermeable membrane, and causing the chitosan to precipitate such as by changing the pH to form the core matrix. Alternatively, the chitosan in solution is precipitated to form the core matrix containing cells, and the core matrix is encapsulated in a semipermeable membrane.Type: GrantFiled: February 16, 1999Date of Patent: October 31, 2000Assignee: Brown University Research FoundationInventors: Patrick Aebischer, Beth A. Zielinski
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Patent number: 6133004Abstract: A bioreactor carrier is provided composed of a water absorption gel of a crosslinked N-vinylcarboxamide resin which has a great moisture content and excellent physical strength, is not eroded by microorganisms and is easily mass-produced on an industrial scale. The gel is obtained by swelling and gelling a crosslinked N-vinylcarboxamide resin made from an N-vinylcarboxamide such as N-vinylacetoamide. The swollen gel may be in the form of beads of 1.0 to 20 mm, and the resin when swollen with water has a water absorption coefficient of 500 to 3500%. Resin beads may be swollen in a suspension of a biocatalyst such as animal cells, plant cells, microorganisms or protozoans to bind and immobilize the biocatalyst to form a bioreactor. The microorganisms can be nitrate bacteria, denitrification bacteria or Hyphomycetes, and the bioreactor may be used to treat waste water or for deodorizing.Type: GrantFiled: March 9, 1998Date of Patent: October 17, 2000Assignee: Nisshinbo Industries, Inc.Inventors: Takaya Sato, Tsutomu Uehara, Hiroshi Yoshida
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Patent number: 6126936Abstract: Microcapsules and composite microreactors are prepared that immunoisolate living cells such as islet cells or genetically engineered cells. A reduced volume microcapsule is formed by coating a gel matrix particle with a polyamino acid of 15,000 daltons or less molecular weight to reduce volume of the particle by at least 30% as compared to volume prior to coating. A composite microreactor includes the microcapsule containing cell embedded in a gel matrix and provides a molecular weight cutoff that prevents molecules larger than about 400,000 daltons from containing the living cell. A double composite microreactor includes an internal particle that includes an internal particle gel matrix containing a living cell and having a coating, a particle that includes the internal particle embedded in a particle gel matrix and a coating, and a gel super matrix in which the particle is embedded. At least one of the coatings is a volume reducing coating of polyamino acid of 15,000 daltons or less molecular weight.Type: GrantFiled: March 10, 1995Date of Patent: October 3, 2000Assignee: BioHybrid Technologies LLCInventors: Robert P. Lanza, Willem M. Kuhtreiber, William L. Chick
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Patent number: 6127448Abstract: The invention provides a biocompatible polymeric coating material, wherein the polymeric material is selected from the group consisting of linear, dendrimeric and branched polymers which contain primary, secondary, tertiary or quaternary amine groups with hydrophobic side chains and which polymers are insoluble, or only slightly soluble, in aqueous solution at a pH range between 3 and 11 and soluble in at least one organic solvent selected from the group consisting of alcohols, acetone, methyl ethyl ketone, tetrahydrofuran, dioxane, chloroform, dichloromethane, hexanes and mixtures thereof.Type: GrantFiled: November 9, 1998Date of Patent: October 3, 2000Assignee: Alomone Labs Ltd.Inventor: Abraham Jacob Domb
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Patent number: 6110902Abstract: The present invention relates to the treatment of conditions associated with neuronal activity. Specifically, the invention is drawn to methods and compositions for administering adenosine to inhibit pain syndromes or epilepsy in a patient.Type: GrantFiled: June 23, 1997Date of Patent: August 29, 2000Inventors: Hanns Mohler, Detlev Boison
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Patent number: 6107102Abstract: A suspension of microfabricated microdevices for use in therapeutic applications is disclosed. The microdevices have a selected shape, and uniform dimensions preferably in the 100 nm to 10 Am range. Also disclosed are microfabrication methods for making such microdevices.Type: GrantFiled: August 7, 1997Date of Patent: August 22, 2000Assignee: Regents of the University of CaliforniaInventor: Mauro Ferrari
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Patent number: 6103255Abstract: Biodegradable and biocompatible porous scaffolds characterized by a substantially continuous polymer phase, having a highly interconnected bimodal distribution of open pore sizes with rounded large pores of about 50 to about 500 microns in diameter and rounded small pores less than 20 microns in diameter, wherein the small pores are aligned in an orderly linear fashion within the walls of the large pores. Methods of preparing polymeric tissue scaffolds are also disclosed.Type: GrantFiled: April 16, 1999Date of Patent: August 15, 2000Assignee: Rutgers, The State UniversityInventors: Howard B. Levene, Christelle M. Lhommeau, Joachim B Kohn
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Patent number: 6103528Abstract: A gelling cell culture medium useful for forming a three dimensional matrix for cell culture in vitro is prepared by copolymerizing an acrylamide derivative with a hydrophilic comonomer to form a reversible (preferably thermally reversible) gelling linear random copolymer in the form of a plurality of linear chains having a plurality of molecular weights greater than or equal to a minimum gelling molecular weight cutoff, mixing the copolymer with an aqueous solvent to form a reversible gelling solution and adding a cell culture medium to the gelling solution to form the gelling cell culture medium. Cells such as chondrocytes or hepatocytes are added to the culture medium to form a seeded culture medium, and temperature of the medium is raised to gel the seeded culture medium and form a three dimensional matrix containing the cells. After propagating the cells in the matrix, the cells may be recovered by lowering the temperature to dissolve the matrix and centrifuging.Type: GrantFiled: April 17, 1998Date of Patent: August 15, 2000Assignees: Battelle Memorial Institute, Medical University of South CarolinaInventors: Yuehuei H. An, Vladimir A. Mironov, Anna Gutowska
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Patent number: 6090793Abstract: Proposed is a mitogen-free substance comprising cross-linked copolymers including 10 to 90 mole % of guluronic acid, the balance being made up of mannuronic acid. The substance has a molecular weight of from 10,000 to 500,000 Daltons. Also proposed are methods for preparing such substances and their use.Type: GrantFiled: August 10, 1994Date of Patent: July 18, 2000Assignee: Monsanto Europe S.A.Inventors: Ulrich Zimmermann, Konrad Federlin, Tobias Zekorn, Gerd Klock
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Patent number: 6083523Abstract: An immunoisolatory vehicle for the implantation into an individual of cells which produce a needed product or provide a needed metabolic function. The vehicle is comprised of a core region containing isolated cells and materials sufficient to maintain the cells, and a permselective, biocompatible, peripheral region free of the isolated cells, which immunoisolates the core yet provides for the delivery of the secreted product or metabolic function to the individual.Type: GrantFiled: September 4, 1998Date of Patent: July 4, 2000Assignees: Brown University Research Foundation, Brown UniversityInventors: Keith E. Dionne, Dwaine F. Emerich, Diane Hoffman, Paul R. Sanberg, Lisa Christenson, Orion D. Hegre, David W. Scharp, Paul E. Lacy, Patrick Aebischer, Alfred V. Vasconcellos, Michael J. Lysaght, Frank T. Gentile
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Patent number: 6080402Abstract: Lipases are immobilized by entrapment in silicon-containing matrices obtained by hydrolysis of alkoxy-silicon compounds in the presence of a catalyst and additives such as proteins, polyhydroxy compounds, insoluble organic polymers and/or insoluble inorganic compounds. The entrapped lipase may be used for treatment of digestive insufficiency in a patient caused by pancreatic disease or cystic fibrosis.Type: GrantFiled: June 12, 1998Date of Patent: June 27, 2000Assignee: Studiengesellschaft Kohle mbHInventors: Manfred T. Reetz, Jorg Simpelkamp, Albin Zonta
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Patent number: 6066331Abstract: A composition useful for preparing vesicles loaded with biological cell-structures, biopolymers and/or -oligomers is prepared by solubilizing amphiphatic material such as a phospholipid in a polar-protic solvent miscible with water, solubilizing biological cell-structures, biopolymers and/or -oligomers in an aqueous medium, mixing the polar-protic solvent containing the amphiphatic material with the aqueous medium containing the biological cell-structures, biopolymers and/or -oligomers, and lyophilizing the resultant mixture to form a dry product. The dry product is hydrated in an aqueous medium to form the loaded vesicles. The polar-protic solvent may be tert-butanol, and the aqueous medium may contain a salt such as sodium chloride, an isoosmotic cryoprotectant such as lactose, sucrose or trehalose, or a mixture of the salt and the cryoprotectant. A medicament for disease treatment is formed by mixing the loaded vesicles with a pharmaceutically acceptable vehicle.Type: GrantFiled: August 13, 1996Date of Patent: May 23, 2000Inventors: Yechezkel Barenholz, Lilianne K. Bar, Dvorah Diminsky, Moshe Baru
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Patent number: 6054142Abstract: A biocompatible cell device having an internal foam scaffold to provide a growth surface for encapsulated cells which produce a biologically active molecule.Type: GrantFiled: August 1, 1996Date of Patent: April 25, 2000Assignee: Cyto Therapeutics, Inc.Inventors: Rebecca Li, Tyrone F. Hazlett
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Patent number: H1986Abstract: A method for removing sulfur from liquid compositions containing aliphatic or cylic organic sulfur-containing compounds, e.g., dibenzothiophene includes activating the sulfur-containing compound by oxidizing either the organic sulfur or adjacent carbon atoms in the presence of a suitable active biocatalyst (ie., microorganism, enzyme, etc.) followed by treating of the activated compound by techniques such as fluidized catalytic cracking so as to remove the sulfur therefrom.Type: GrantFiled: May 7, 1999Date of Patent: August 7, 2001Inventors: Ronald M. Atlas, David J. Boron, William R. Deever, Axel R. Johnson, Beverly Lynn McFarland, Jarold A. Meyer