Enzyme Or Microbial Cell Is Entrapped Within The Carrier (e.g., Gel, Hollow Fibre) Patents (Class 435/182)
  • Patent number: 6656489
    Abstract: A biodegradable, biocompatible porous matrix as a scaffold for tissue engineering cartilage is formed of a copolymer of a polyalkylene glycol and an aromatic polyester such as a polyethylene glycol/polybutylene terephtalate copolymer. A ceramic coating such as a calcium phosphate coating may be provided on the scaffold by soaking the scaffold in a solution containing calcium and phosphate ions. A composite scaffold which is preferably a two-layer system may be formed having an outer surface of a layer of the porous matrix formed of the copolymer, and an outer surface of a layer of a ceramic material. The composite scaffold may be prepared by casting the copolymer on top of the ceramic material in a mould. Cells are preferably seeded on the scaffold prior to implanting, and the scaffold may contain bioactive agents that are released on degradation of the scaffold in vivo.
    Type: Grant
    Filed: February 4, 2000
    Date of Patent: December 2, 2003
    Assignee: IsoTis N.V.
    Inventors: Tahir Mahmood, Jens Uwe Riesle, Clemens Antoni van Blitterswijk
  • Patent number: 6649384
    Abstract: 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: Grant
    Filed: July 5, 2001
    Date of Patent: November 18, 2003
    Assignee: Islet Technology, Inc.
    Inventors: Stephen E. Walsh, Monte R. Canfield, Nancy J. Drake
  • Patent number: 6641832
    Abstract: An angiogenic material is prepared which promotes extensive vascularization when implanted in animal tissue. 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. Preferably, the angiogenic material consists of a biocompatible polymer and a vascularizing compound consisting of polymerizable compounds capable of forming anions. Microspheres containing the angiogenic material may be used to assist in recovery of ischemic heart muscle by injection of the microspheres into the heart muscle or blood vessels serving the ischemic area. Also disclosed is a method of forming small microcapsules and microspheres by passing cell aggregates or air bubbles through layers of a density gradient.
    Type: Grant
    Filed: December 20, 2000
    Date of Patent: November 4, 2003
    Inventors: Michael Vivian Sefton, Julia Elizabeth Babensee, Michael Humphrey May
  • Patent number: 6642037
    Abstract: An enzymatically active reusable sponge or foam, capable of regeneration with oximes, made of a polymer such as polyurethane is prepared for detoxification of hazardous compounds such as organophosphorus and organosulfur compounds. The foam or sponge contains a plurality of enzymes including enzymes selected from acetylcholinesterase, butyrylcholinesterase, triesterase, pseudocholinesterase, organophosphate hydrase, phosphotriesterase, paraoxonase and organophosphorus and organosulfur hydrolyzing enzymes. The sponge or foam may additionally contain activated carbon and an enzyme reactivation compound. A kit can be formed containing the sponge or foam and the compound for enzyme reactivation. The enzymatically active foam or sponge may be prepared using a two chamber device where enzymes and prepolymer are passed from separate chambers into a static mixing stator and are subjected to low shear mixing and extrusion to form by the sponge or foam.
    Type: Grant
    Filed: April 26, 2000
    Date of Patent: November 4, 2003
    Assignee: The United States of America as represented by the Secretary of the Army
    Inventors: Richard K. Gordon, Bhupendra P. Doctor, Ashima Saxena, Shawn R. Feaster, Donald Maxwell, Michelle Ross, David Lenz, Keith Lejeune, Alan Russell
  • 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
  • Publication number: 20030186405
    Abstract: The present invention relates to a method of producing micro and nano-porous polymeric articles with well-defined pore structures.
    Type: Application
    Filed: April 1, 2002
    Publication date: October 2, 2003
    Applicant: The Ohio State University Research Foundation
    Inventors: L. James Lee, Siyi Lai
  • Patent number: 6627422
    Abstract: A device is provided containing cells or tissue distributed on a filamentous cell-supporting matrix which is encapsulated by a semi-permeable membrane which can be immunoisolatory. The matrix may be formed of a plurality of monofilaments twisted into yarn that is in non-woven strands, or of the monofilaments or yarn woven into a mesh. Configurations of the matrix include a hollow cylinder, tube, solid cylinder or cord. A coating of extracellular matrix molecules may be on the matrix, or the matrix may be treated with plasma irradiation to enhance cell adhesion. The device can be made by inserting the matrix in a hollow membrane tube, injecting cells or tissue into the tube and sealing ends of the tube. The device is particularly useful for implantation into a mammalian host to provide therapy resulting from a biologically active molecule produced by the cells and tissue.
    Type: Grant
    Filed: December 21, 2000
    Date of Patent: September 30, 2003
    Assignee: Neurotech S.A.
    Inventors: Rebecca Li, David Rhein
  • Patent number: 6623749
    Abstract: Polyhydroxyalkanoate (PHA) that contains a pyrogen such as an endotoxin due to a process of producing the PHA is treated to remove the pyrogen by a process that does not affect the inherent chemical and physical properties of the PHA to obtain a biocompatible PHA. PHA produced by fermentation with a Gram negative bacteria can be treated with an oxidizing agent such as hydrogen peroxide or benzoyl peroxide to reduce the endotoxin content to less than 20 endotoxin units/gram of PHA to produce PHA that does not elicit an acute inflammatory response when implanted in an animal. The PHA may have a melting point or glass transition temperature less than 136° C., and can be chemically modified or derivatized such as by covalently coupling an attachment or targeting molecule.
    Type: Grant
    Filed: March 28, 2001
    Date of Patent: September 23, 2003
    Assignee: Metabolix, Inc.
    Inventors: Simon F. Williams, David P. Martin, Tillman Gerngross, Daniel M. Horowitz
  • Patent number: 6617151
    Abstract: A method is provided for closing a containment device that involves wetting at least a portion of a permeable polymeric membrane such as tubular membrane with a liquid such as a cell suspension or drug formulation the device is being filled with, and applying heat to at least a portion of a wetted thermoplastic polymer in association with the membrane to form a “wet seal” closure. The thermoplastic polymer melts at a lower temperature than the polymeric membrane and the melted polymer integrates with the membrane by flowing along surfaces and into available interstices of the membrane to form a cell-tight closure when the polymer cools below its melt temperature. The application of heat may be accompanied by slight pressure, and a heat sink may be applied to limit heat transfer beyond the closure region to the membrane.
    Type: Grant
    Filed: February 29, 2000
    Date of Patent: September 9, 2003
    Assignee: Gore Enterprise Holdings, Inc.
    Inventors: Steven C. Newman, Brian H. Kram, Terry A Hubbard
  • Patent number: 6616954
    Abstract: The present invention is an encapsulated yeast composite comprising a core comprising yeast and a soluble coating comprising polyethylene glycol having a molecular weight less than 3050. The yeast includes Saccharomyces cerevisiae. The encapsulated composites are useful in the production of food compositions and food products.
    Type: Grant
    Filed: March 14, 2002
    Date of Patent: September 9, 2003
    Assignee: Balchem Corporation
    Inventors: Vernetta L. Dally, David E. Martin, Carl J. Pacifico, Paul H. Richardson
  • Patent number: 6616912
    Abstract: A bi-component microporous hollow fiber membrane structure is provided for in vivo propagation of cells and use in testing of the effect of medical treatments on cells within the structure. The structure has an inner structure fabricated from a first bio-compatible polymer and an outer structure fabricated from a different polymer that has a lower tendency for cell adhesion than the inner structure polymer. In this way, the inner structure can be selected to optimize cell propagation and the outer structure can be fabricated from a polymer which optimizes the removal of the bi-component structure from its implanted location. The inner and outer structures may have a pore size between 10 and 1000 Angstroms and 100 and 2000 Angstroms, respectively, and be formed from polysulfone or polyether sulfone and polyvinyledene difuoride, respectively. The membrane structure can form macrocapsules containing media and living cells for implanting.
    Type: Grant
    Filed: January 5, 2001
    Date of Patent: September 9, 2003
    Assignee: Spectrum Laboratories, Inc.
    Inventors: Roy T. Eddleman, Jesus Martinez
  • Publication number: 20030148483
    Abstract: Disclosed is a method of removing residual enzymes when microencapsulating enzymes, and more particularly, for inactivating enzymes remaining in an uncapsulated form during microencapsulation of enzymes by treating dispersion fluid of microcapsules containing enzymes with ozone, together with removal of microorganisms harmful to human beings, where the ozone treatment is conducted for 1-10 min with 1-10 ppm of ozone generated from a UV lamp in a range from 150 to 200 nm wavelength.
    Type: Application
    Filed: July 17, 2002
    Publication date: August 7, 2003
    Inventors: Hae-Soo Kwak, Joon Bum Lee
  • Patent number: 6596310
    Abstract: 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: Grant
    Filed: August 23, 2000
    Date of Patent: July 22, 2003
    Assignees: Board of Trustees operating Michigan State University, University of Michigan
    Inventors: Kuo-Chuan Karen Chou, Henry Y. Wang
  • Publication number: 20030113903
    Abstract: The present invention is a method of remedying contaminated soil comprises: providing microorganisms capable of degrading soil contaminants to contaminated soil, in which the microorganisms is supported on a carrier; and providing nutrients for the microorganisms to the contaminated soil on the condition that the nutrients can be gradually released, and a microorganism preparation for remedying soil.
    Type: Application
    Filed: September 10, 2002
    Publication date: June 19, 2003
    Applicant: FUJI PHOTO FILM CO., LTD.
    Inventor: Hideo Miyazaki
  • Patent number: 6576451
    Abstract: An oligomer is provided having a polyalkylene glycol main structure, a polymeric double bond group arranged at both ends of the main structure, and a sub-structure arranged between the main structure and each polymeric double bond group. The sub-structures lengthen the main structure, and are composed of a urethane bond and an ethyleneoxy, or a urethane bond, an ethyleneoxy and a propyleneoxy. The introduction of urethane bonds causes crystallization (network formation) with the urethane bonds themselves so that a hydrous gel resulting from polymerizing the oligomer has increased flexibility, strength and erosion resistance. As a result, even though the main structure is lengthened to increase capacity to entrap microorganisms, the strength of the hydrous gel is not reduced. The ethyleneoxy weakens hydrophobicity of urethane regions to improve affinity of the gel for microorganisms. Microorganisms can adhere to and grow on the surface of a hydrous gel produced by polymerizing the oligomer.
    Type: Grant
    Filed: August 25, 2000
    Date of Patent: June 10, 2003
    Assignees: Hitachi Plant Engineering & Construction Co., Ltd., Shin-Nakamura Chemical Co., Ltd.
    Inventors: Tatsuo Sumino, Naomichi Mori, Tamio Igarashi, Hiroyoshi Emori, Minoru Kayanoki, Takayuki Nakamura, Ryuichi Matsuyama, Tsutomu Minaki
  • 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: 6551806
    Abstract: Enzyme-containing polymers are prepared by an anhydrous process of direct reaction of an enzyme in organic solution with crosslinking organic compounds having terminal reactive groups. In a first step, the enzyme is reacted in an organic solvent with a bifunctional monomer such as p-phenylene diisocyanate, 4-methyl-m-phenylene diisocyanate or 4,4′-methylenebisphenyl diisocyanate, and in a second step a bifunctional amine such as N-phenylethylenediamine, 1,6-diaminohexane, N,N′-diethyl-ethylenediamine or 1,4-diaminobutane is added. The enzyme-containing polymers are used as catalysts in chemical reactions such as acylation or enantioselective acylation of alcohols.
    Type: Grant
    Filed: January 2, 2001
    Date of Patent: April 22, 2003
    Assignee: BASF Aktiengesellschaft
    Inventor: Rainer Stürmer
  • Patent number: 6552172
    Abstract: The present invention provides fibrin nanoparticles having a mean diameter of 200-2000 nm. The present invention provides also methods for preparing fibrin particles of various sizes, including fibrin nanoparticles and fibrin microbeads. The present invention further provides compositions comprising fibrin particles and an agent, wherein the agent is coupled to the amine or carboxy moieties on the surface of the fibrin particles. In addition the present invention provides a composition comprising fibrin nanoparticles and an agent, wherein the agent is admixed with the fibrin nanoparticles. Still further, the present invention provides a method for introducing an agent into a cell, a method for isolating stem and/or progenitor cells from a biological sample, as well as a composition comprising fibrin particles bound to stem and/or progenitor cells.
    Type: Grant
    Filed: August 30, 2001
    Date of Patent: April 22, 2003
    Assignee: Habto Biotech, Inc.
    Inventors: Gerard Marx, Raphael Gorodetsky
  • Patent number: 6544763
    Abstract: Enzyme granules are provided in which an enzyme is rapidly eluted, without insoluble remnants, and generation of powdery dust is suppressed, and which granules have a property such that classification phenomenon generated among the granules in a detergent composition is less likely to take place, in a case where the enzyme granules are formulated together with other components in a detergent. The enzyme granule comprise (A) water-insoluble substance and or a slightly water-soluble substance; (B) a water-soluble binder; and (C) an enzyme. A dye may also be present for coloring. The content of (A) component is 45% by weight or more, and the enzyme granules have an average particle size of from 150 to 500 &mgr;m and a bulk density of from 500 to 1,000 g/L, and have a structure such that more amount of (B) component is present near the surface of the enzyme granules than in the inner portion thereof. The enzyme granule may be aggregated to form an enzyme granule aggregate.
    Type: Grant
    Filed: October 31, 2001
    Date of Patent: April 8, 2003
    Assignee: Kao Corporation
    Inventors: Yoshinobu Imaizumi, Koichi Ohori, Itsuro Tsukahara, Hiroyuki Yamashita
  • Patent number: 6511854
    Abstract: An improved electrochemical method for disassociating a biological binding partner from a corresponding second biological binding partner associated with a waveguide surface, the electrochemical method involving the application of an electrical potential to said waveguide surface (118), the improvement comprising: applying the electrical potential to the waveguide surface (118) as a square wave polarization function. Preferably, the waveguide surface is comprised of indium tin oxide. The biological binding partners are selected from the group consisting of antigen-antibody, avidin-biotin, enzyme-substrate, cell receptor-substrate/analog, antibody/anti-antibody, DNA, RNA, and fragments thereof. The antigen may be comprised of an epitope. The epitope is produced by a solid phase peptide synthesis performed on said waveguide surface (118).
    Type: Grant
    Filed: June 12, 2000
    Date of Patent: January 28, 2003
    Assignee: The UAB Research Foundation
    Inventors: Alexander N. Asanov, W. William Wilson, Philip B. Oldham
  • Patent number: 6503731
    Abstract: Fibrin microbeads are prepared containing extensively cross-linked fibrin (ogen) without using glutaraldehyde. The fibrin microbeads are preferably prepared by containing an aqueous solution containing fibrinogen, thrombin and Factor XIII with an oil heated to about 50-80° C. to form an emulsion and mixing the emulsion at 50-80° C. until fibrin microbeads containing extensively cross-linked fibrin (ogen) are obtained. The fibrin microbeads may have a diameter of about 50-200 microns and can contain a bioactive agent. The fibrin microbeads are used for binding cells such as when culturing or separating one cell type from another, or when transplanting cells or engineering tissue.
    Type: Grant
    Filed: September 15, 1998
    Date of Patent: January 7, 2003
    Assignee: Hadasit Medical Research & Development Ltd.
    Inventors: Gerard Marx, Raphael Gorodetsky
  • Patent number: 6492163
    Abstract: A cell tube for ex vivo culturing animal cells and a multiple roller tube cell culture system are disclosed. Suitable for use in culturing cells, the tube has at its opposite end walls two openings through which culture media can come in and out. The openings are eccentrically located at corresponding positions in contact with the edge sides of the end walls. The system has a plurality of roller drums on which a multitude of cell tubes are assembled. As the roller drums are rotated, cells adhering to each tube experience a nutrient-rich state and aerobic starvation, repeatedly. In the nutrient-rich state, the cells are grown flourishingly. When subjected to starvation, cells select metabolism pathways for utilizing carbon sources effectively, produce lactate at a low rate and can maintain a constant pH, because they are in direct contact with air. The system makes cells adhere to the wall of cell tubes and provides air directly to cell surfaces.
    Type: Grant
    Filed: September 19, 2001
    Date of Patent: December 10, 2002
    Assignee: Core Biotech Co., Ltd.
    Inventors: Kwang Hyun Yoo, Wan Kyu Choi, Sung Ho Shin
  • Patent number: 6479066
    Abstract: A device and method of using the device are provided for implanting cell cultures in a host. The device is formed of a deformable body, a microporous membrane and a sealable port. The shape of the body which is preferably rounded can be altered by applying stress or pressure, The body comprises a continuous wall constructed of a mesh material, and the membrane lines a surface of the body. The wall and membrane define an enclosed three-dimensional cavity for containing a cell culture. Openings of the membrane allow for passage of therapeutic substances produced by the cells and nutrients or biomolecules produced by host. The sealable port is configured for adding a cell culture to the cavity, and is formed of a material that is capable of resealing after being punctured with a needle. Because the device is deformable, it can be compressed and placed in an implantation site where it expands to conform to contours of tissue surrounding the site.
    Type: Grant
    Filed: December 16, 1999
    Date of Patent: November 12, 2002
    Assignee: RST Implanted Cell Technology, LLC
    Inventor: Stanley D. Harpstead
  • Patent number: 6475382
    Abstract: A treatment unit is disclosed for treating a fluid in continuous mode. This treatment unit provides the opportunity to carry out simultaneously an enzymatic transformation and a capture of a fluid element. The unit has a reservoir with a fluid inlet for receiving a fluid to be treated and a fluid outlet for releasing a treated fluid. The unit also has removable cassettes provided with a reactive material for treating the fluid and two spaced-apart baffle walls in the reservoir for regulating the flow of the fluid therein. The unit further has a reaction chamber defined between each of the two spaced-apart baffles walls. The reaction chamber has an opening for removably inserting therein the cassette. Yet, the unit further has mounting means for mounting the cassette in a reaction chamber spaced-apart from the two baffle walls, whereby a cassette is disposed between two spaced-apart baffle walls and causes the fluid to flow in a zigzag pattern thus further regulating the flow of the fluid.
    Type: Grant
    Filed: December 19, 2000
    Date of Patent: November 5, 2002
    Assignee: CO2 Solution Inc.
    Inventor: Carmen Parent
  • 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: 6465226
    Abstract: 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: Grant
    Filed: October 19, 1998
    Date of Patent: October 15, 2002
    Inventor: Ulrich Zimmermann
  • Patent number: 6465227
    Abstract: A process is presented for producing spherical particles containing microorganism cells having desired enzyme activity. The process comprises the steps of mixing the cells directly with a primary or secondary amine-containing polymer, combining the resulting mixture with an organic solvent to form a two-phase system, and then adding a bifunctional cross-linking agent to yield the spherical particles. The preferred enzyme activities are D-amino acid oxidase and glutarylacylase activities.
    Type: Grant
    Filed: April 3, 2000
    Date of Patent: October 15, 2002
    Assignee: Biochemie Gesellschaft m.b.H.
    Inventors: Arno Reichert, Waander Riethorst, Franz Knauseder, Norbert Palma
  • Publication number: 20020142413
    Abstract: A tissue engineering scaffold for cell, tissue or organ growth comprises a biocompatible porous polyurethane cellular material comprising a plurality of substantially spherical voids of diameter from 20 to 300 microns, preferably 80 to 200 microns, interconnected by generally elliptically shaped pores. The cellular material has a void content of from 85% to 98% and a surface area to volume of from 5 to 400 mm2/mm3, ideally from 20 to 80 mm2/mm3.
    Type: Application
    Filed: November 6, 2001
    Publication date: October 3, 2002
    Applicant: SALVIAC LIMTED
    Inventors: Eamon Brady, Ann Marie Cannon, Fergal Farrell, Gerard McCaffrey
  • 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
  • Publication number: 20020110882
    Abstract: The invention provides a temperature-stable liquid droplet comprising a temperature-stable hydrocolloid membrane. The hydrocolloid is selected from low methoxy pectin, Konjac mannan, sodium alginate, or a mixture thereof. The membrane encapsulates a droplet of an edible product or a droplet containing a microorganism, an enzyme or a cell.
    Type: Application
    Filed: September 29, 1999
    Publication date: August 15, 2002
    Inventor: DR. AMOS NUSSINOVITCH
  • Patent number: 6426214
    Abstract: Cell encapsulating devices capable of maintaining large numbers of viable cells are provided containing an inert, substantially cell-free core that displaces cells, a permeable membrane and a zone for maintaining cells. The permeable membrane surrounds the core such that the zone of cells is bounded by the core and the permeable membrane. A preferred device contains a polytetrafluoroethylene permeable membrane and a flexible polymer core having a plurality of ridges and valleys running lengthwise along the core. The cell zone may contain support means for cell attachment and the core may have an outer boundary containing a material that promotes cell adhesion. Preferably, the cell zone has a thickness such that at least about 10% of the cells, more preferably at least about 50% or 80%, in a cell layer located closest to the outer boundary of the core remain viable. The thickness is preferably less than 500 microns such as 25 to 250 microns or 50 to 100 microns.
    Type: Grant
    Filed: November 8, 1999
    Date of Patent: July 30, 2002
    Assignee: Gore Enterprise Holdings, Inc.
    Inventors: Mark D. Butler, Stanley L. Mish
  • Publication number: 20020090690
    Abstract: A microporous hollow fiber membrane structure for use in the in vivo testing of the effect of medical treatments on cells within the structure. The structure has an inner portion fabricated from a first bio-compatible polymer and an outer structure fabricated from a different polymer than the inner structure. In this way, the inner structure can be selected to optimize cell propagation and the outer structure can be fabricated from a polymer which optimizes the removal of the bi-component structure from its implanted location.
    Type: Application
    Filed: January 5, 2001
    Publication date: July 11, 2002
    Inventors: Roy T. Eddleman, Jesus Martinez
  • Patent number: 6413749
    Abstract: Granules are prepared containing an admixture of protein and starch layered over an inert particle. 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. The admixture may also contain sugar such as sucrose. A ratio of corn starch to sugar much greater than 1:1 such as in a range of about 5:1 to about 15:1 is preferred. A coating layer may be between the inert particle and the admixture and/or over the admixture. Methods that may be used in preparing the granules include pan-coating, fluid-bed coating, prilling, disc granulation, spray drying, extrusion, centrifugal extrusion, spheronization, drum granulation and high shear agglomeration.
    Type: Grant
    Filed: October 27, 1999
    Date of Patent: July 2, 2002
    Assignee: Genencor International, Inc.
    Inventors: Nathaniel T. Becker, Thomas S. Green
  • Patent number: 6410287
    Abstract: Enzyme granules are provided in which an enzyme is rapidly eluted, without insoluble remnants, and generation of powdery dust is suppressed, and which granules have a property such that classification phenomenon generated among the granules in a detergent composition is less likely to take place, in a case where the enzyme granules are formulated together with other components in a detergent. The enzyme granule comprise (A) water-insoluble substance and or a slightly water-soluble substance; (B) a water-soluble binder; and (C) an enzyme. A dye may also be present for coloring. The content of (A) component is 45% by weight or more, and the enzyme granules have an average particle size of from 150 to 500 &mgr;m and a bulk density of from 500 to 1,000 g/L, and have a structure such that more amount of (B) component is present near the surface of the enzyme granules than in the inner portion thereof. The enzyme granule may be aggregated to form an enzyme granule aggregate.
    Type: Grant
    Filed: June 9, 2000
    Date of Patent: June 25, 2002
    Assignee: Kao Corporation
    Inventors: Yoshinobu Imaizumi, Koichi Ohori, Itsuro Tsukahara, Hiroyuki Yamashita
  • 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: 6391576
    Abstract: The present invention provides a method for isolating a microbe whereby a sample of microbe cells is encapsulated in agarose gel particulates, wherein some of the particulates contain a single cell, and the other particulates contain more than one cell; incubating the particulates in nutritional and environmental conditions that enable the microbe contained in the sample solution that can grow on a plate of a plate culture method to grow in the agarose gel particulate; and isolating the particulates having single cells from the group of the particulates having more than one cell.
    Type: Grant
    Filed: March 3, 2000
    Date of Patent: May 21, 2002
    Assignees: Japan Bioindustry Association, Ajinomoto Co., Inc., Agency of Industrial Science and Technology
    Inventors: Takayasu Tsuchida, Akira Manome, Ryuichiro Kurane
  • Patent number: 6387693
    Abstract: Cartilage tissue and implants comprising 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 means of 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). The cells settle on such a plate (7) and the cartilage tissue growing in the cell space (1).
    Type: Grant
    Filed: April 18, 2001
    Date of Patent: May 14, 2002
    Assignee: Sulzer Orthopedics Ltd.
    Inventors: Franz Rieser, Werner Muller, Pedro Bittmann, Pierre Mainil-Varlet, Christoph P. Saager
  • Patent number: 6379909
    Abstract: The invention relates to a method of evaluating the immunological status of a subject comprising the steps of 1) determining the content of an antibody in a liquid sample from the subject using an immunoassay, wherein the reaction between the antibody of the sample and a ligand in the form of an antigen, an antibody or a hapten, the ligand being directed to the Fab region of the sample antibody, is carried out in the presence of other constituents of the sample to obtain a measurement 1, 2) determining the content of an antibody in the liquid sample using an immunoassay, wherein the reaction between the antibody of the sample and a ligand in the form of an antigen, an antibody or a hapten, the ligand being directed to the Fab region of the sample antibody, is carried out in the absence of other constituents of the sample to obtain a measurement 2, and 3) interrelating measurements 1 and 2 to express the interference and using the interference as a parameter for evaluating the immunological status of the subje
    Type: Grant
    Filed: June 24, 1999
    Date of Patent: April 30, 2002
    Assignee: Alk-Abello A/S
    Inventors: Hans-Henrik Ipsen, Niels Johansen, R Ikke Morkeberg, Soren Bogestrand, Tine Charlotte Beck
  • Patent number: 6379599
    Abstract: The invention relates to a process for the preparation of molecularly imprinted polymers useful for separation of enzymes, which comprises the steps of reacting a complex of enzyme and affinity monomer, a comonomer and a crosslinker, with a polymerization initiator and a polymerization accelerator at ambient temperature and pressure for a period ranging between 2 to 24 hrs, thereby obtaining a crosslinked polymer, crushing the cross linked polymer obtained to fine particles, adding a solvent and extracting imprinted enzyme from the polymer, obtaining the molecularly imprinted polymer, contacting the imprinted polymer with aqueous solution containing imprinted enzyme or a mixture of imprinted enzyme and other enzymes and isolating the enzyme-adsorbed polymer.
    Type: Grant
    Filed: January 10, 2000
    Date of Patent: April 30, 2002
    Assignee: Council of Scientific and Industrial Research
    Inventors: Alankar Arun Vaidya, Bhalchandra Shripad Lele, Mohan Gopalkrishna Kulkarni, Raghunath Anant Mashelkar
  • Patent number: 6368858
    Abstract: Cells in a matrix or in the matrix in a vessel are grown to form a multicellular aggregate. Pressure is exerted on the growing cells by the matrix or the matrix together with the vessel due to growing cellular mass displacing the matrix. A value representing pressure exerted on the cells is calculated and the pressure is modulated to control growth of the multicellular aggregate, or to produce a multicellular aggregate of a pre-selected size or a pre-selected size and shape. Matrices include agarose, alginate and collagen gels, and the pressure exerted on the cells can be non-isotropic. The cells may be tumor cells, or liver, pancreatic, brain, skin, bone or muscle cells, and cell growth can be in vitro or in vivo. When collagen forms the matrix, the matrix may contain glycosaminoglycan.
    Type: Grant
    Filed: July 22, 1998
    Date of Patent: April 9, 2002
    Assignee: The General Hospital Corporation
    Inventors: Gabriel Helmlinger, Paolo A. Netti, Robert J. Melder, Rakesh K. Jain, Hera Lichtenbeld-Dubois
  • Patent number: 6368804
    Abstract: A method for preserving immobilized or unimmobilized microbial cells having nitrilase activity and for stabilizing the 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 about 0.10 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 uninmmobilized 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), Acidovorax facilis 72W (ATCC 55746), and transformed microbial cells having nitrilase activity, preferably E.
    Type: Grant
    Filed: July 12, 2000
    Date of Patent: April 9, 2002
    Assignee: E. I. du Pont de Nemours & Company
    Inventors: Arie Ben-Bassat, Robert Dicosimo, Robert Donald Fallon
  • Patent number: 6365385
    Abstract: 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. Microcapsules containing cells may be incubated with a physiologically acceptable salt to increase durability of the microcapsules. 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.
    Type: Grant
    Filed: December 1, 1999
    Date of Patent: April 2, 2002
    Assignee: Duke University
    Inventor: Emmanuel C. Opara
  • Patent number: 6362011
    Abstract: Graphitic nanotubes, which include tubular fullerenes (commonly called “buckytubes”) and fibrils, which are functionalized by chemical substitution, are used as solid supports in electrogenerated chemiluminescence assays. The graphitic nanotubes are chemically modified with functional group biomolecules prior to use in an assay. Association of electrochemiluminescent ruthenium complexes with the functional group biomolecule-modified nanotubes permits detection of molecules including nucleic acids, antigens, enzymes, and enzyme substrates by multiple formats.
    Type: Grant
    Filed: February 2, 1999
    Date of Patent: March 26, 2002
    Assignee: Meso Scale Technologies, LLC
    Inventors: Richard J. Massey, Mark T. Martin, Liwen Dong, Ming Lu, Alan Fischer, Fabian Jameison, Pam Liang, Robert Hoch, Jonathan K. Leland
  • Patent number: 6352707
    Abstract: Immune recognition of a transplant such as tissue implanted in a host mammal is obscured by encapsulating the transplant in a hydrogel matrix containing gelatin, dextran, at least one nitric oxide inhibitor and polar amino acids. The polar amino acids increase rigidity of the matrix and allow direct injection of the encapsulated transplant into a mammal without further immunosuppression. Preferably, the nitric oxide inhibitor is a combination of L-cysteine and an L-arginine analogue such as aminoguanidine, and the polar amino acids are a combination of L-glutamic acid, L-lysine and L-arginine. The matrix may also contain a superoxide inhibitor such as EDTA. Implanting can be carried out by applying a buffer medium containing a nitric oxide inhibitor to an implant site, implanting the encapsulated transplant, and applying to the implant site a buffer medium which may contain a nitric oxide inhibitor. The buffer medium may also contain a superoxide inhibitor.
    Type: Grant
    Filed: July 1, 1999
    Date of Patent: March 5, 2002
    Inventor: Anton-Lewis Usala
  • Patent number: 6352837
    Abstract: A sterilization indicator is useful for testing the effectiveness of sterilization procedures that disinfect objects by contacting them with a liquid sterilization procedure. The indicator includes an outer container having an open end and a cover material associated with the open end that is impermeable to liquids and bacteria. An enzyme-gel matrix is coated on a surface within the outer container that comprises a biologically inert polymeric gel and a source of an active enzyme dispersed within the gel. The enzyme has an activity that is correlated with the survival of at least one test microorganism that is commonly used to monitor the effectiveness of a sterilization procedure. A breakable ampoule within the outer container contains a substrate that is capable of reacting with any active enzyme remaining after the indicator has been subjected to a sterilization procedure to provide a detectable indication that the sterilization procedure was ineffective.
    Type: Grant
    Filed: February 22, 1999
    Date of Patent: March 5, 2002
    Assignee: 3M Innovative Properties Company
    Inventors: Kelvin J. Witcher, Lewis P. Woodson
  • Patent number: 6337198
    Abstract: 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: Grant
    Filed: June 27, 2000
    Date of Patent: January 8, 2002
    Assignee: Rutgers, The State University
    Inventors: Howard B. Levene, Christelle M. Lhommeau, Joachim B Kohn
  • Publication number: 20010055797
    Abstract: A sol and a method for forming a sol that can be used to immobilize biological materials and/or form robust macroporous gels. As needed, sols that are compatible with biological materials can be produced. Also as needed, robust macroporous gels can be formed by introducing dispersants to suitable sols.
    Type: Application
    Filed: February 20, 2001
    Publication date: December 27, 2001
    Inventors: John F.T. Conroy, Pamela M. Norris, Mary E. Power
  • Publication number: 20010051367
    Abstract: Unique single walled nanotube compositions and methods for making the composition wherein the nanotubes encloses foreign material capable of forming thread-like material having a solid form at ambient temperatures and pressures.
    Type: Application
    Filed: July 15, 1999
    Publication date: December 13, 2001
    Inventor: CHING-HWA KIANG
  • Patent number: 6325934
    Abstract: Sewage waste digestive bacteria and enzymes are incorporated into a slow release material and delivered to the site of the waste to digest the solid waste. The slow release material is made heavy so the enzymes and bacteria will be delivered to the sludge in the bottom of a sewage digester chamber and made fat soluble so that the enzymes and bacteria will be delivered to the grease in the waste system to be digested. This selective delivery system prevents the enzymes and bacteria from being diluted in grey water rendering them less effective and discharged from the sewage system without digesting waste.
    Type: Grant
    Filed: May 9, 2000
    Date of Patent: December 4, 2001
    Inventors: James Francis Tobey, Jr., Raymond D. Stapleton, Jr.
  • Patent number: RE38027
    Abstract: 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: Grant
    Filed: June 30, 1999
    Date of Patent: March 11, 2003
    Assignee: The Rogosin Institute
    Inventors: Kanti Jain, Albert L. Rubin, Barry Smith