Entrapped Within The Carrier, E.g., Gel, Hollow Fibre, Etc. Patents (Class 530/817)
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Patent number: 8771720Abstract: Polyhydroxyalkanoates (PHAs) from which pyrogen has been removed are provided. PHAs which have been chemically modified to enhance physical and/or chemical properties, for targeting or to modify biodegradability or clearance by the reticuloendothelial system (RES), are described. Methods for depyrogenating PHA polymers prepared by bacterial fermentation processes are also provided, wherein pyrogens are removed from the polymers without adversely impacting the polymers' inherent chemical structures and physical properties. PHAs with advantageous processing characteristics, including low melting points and/or solubility in non-toxic solvents, are also described. The PHAs are suitable for use in in vivo applications such as in tissue coatings, stents, sutures, tubing, bone, other prostheses, bone or tissue cements, tissue regeneration devices, wound dressings, drug delivery, and for diagnostic and prophylactic uses.Type: GrantFiled: July 10, 2012Date of Patent: July 8, 2014Assignee: Metabolix, Inc.Inventors: Simon F. Williams, David P. Martin, Tillman Gerngross, Daniel M. Horowitz
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Patent number: 8697111Abstract: An osteochondral plug includes a first scaffold and a second scaffold. The first scaffold may be a solid scaffold containing one or more pendant reactive functional groups. The second scaffold capable of reacting with the one or more pendant reactive functional groups of the first scaffold.Type: GrantFiled: May 12, 2010Date of Patent: April 15, 2014Assignee: Covidien LPInventors: Arpan Desai, Timothy Sargeant, Atu Agawu, Joshua Stopek
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Patent number: 8679808Abstract: The present invention discloses a method for fabricating aerogels, a method for fabricating surface-modified aerogels, and a method for fabricating biocomposites. Take the fabricating method of biocomposites for example, first, a precursor solution is provided and the precursor solution comprises a hydrophilic ionic liquid, a catalyzed hydrolysis and/or condensation reagent, at least one biomolecule. Next, a curing process is performed for the precursor solution to hydrolyze and polymerize the at least one alkoxide monomer and/or aryloxide monomer to wrap at least one biomolecule and thus form biocomposite. Afterwards, an extracting process is performed by a solvent for the biocomposite to substitute the ionic liquid in the biocomposite. Finally, a drying process for the biocomposite is carried out after the extracting process so as to remove the solvent in the biocomposite. Therefore, the biocomposite is formed.Type: GrantFiled: November 17, 2010Date of Patent: March 25, 2014Assignee: Chung Yuan Christian UniversityInventors: Yui-Whei Chen-Yang, Yen-Kuang Li, Ching-Yao Yuan, Tzong-Yuan Wu
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Patent number: 8481334Abstract: The invention features a method of attaching a ligand that has a free carboxyl group to a solid support by adding an amino group to the ligand to form a ligand-amino derivative, converting the ligand amino derivative to a ligand sulfhydryl derivative, attaching the ligand sulfhydryl derivative to a protein to form a ligand-linker-protein conjugate, and applying the ligand-linker-protein conjugate to the solid support. The method is particularly useful for immobilizing small molecule ligands having a free carboxyl group, such as cloxicillin, to a lateral-flow test strip, in order to make a detection zone on the test strip that exhibits a clear signal and enhanced sensitivity.Type: GrantFiled: March 31, 2008Date of Patent: July 9, 2013Assignee: Charm Sciences, Inc.Inventor: Steven J. Saul
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Patent number: 8202833Abstract: The present invention provides method and materials for forming a polymeric matrix having improved biocompatible properties. A polymerization accelerator is provided that includes an N-vinyl group and a biocompatible functional group. The polymerization accelerator is particularly useful for the polymerization of macromers, which can be used to form biocompatible polymeric coatings on the surface of biological materials, such as cells and tissue.Type: GrantFiled: November 26, 2003Date of Patent: June 19, 2012Assignee: Surmodics, Inc.Inventors: Dale G. Swan, Stephen J. Chudzik, Ronald F. Ofstead
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Patent number: 8025901Abstract: Disclosed are hydrogels wherein a polymer matrix is modified to contain a bifunctional poly(alkylene glycol) molecule covalently bonded to the polymer matrix. The hydrogels can be cross-linked using, for example, glutaraldehyde. The hydrogels may also be crosslinked via an interpenetrating network of a photopolymerizable acrylates. The hydrogels may also be modified to have pharmacologically-active agents covalently bonded to the poly(alkylene glycol) molecules or entrained within the hydrogel. Living cells may also be entrained within the hydrogels.Type: GrantFiled: November 10, 2009Date of Patent: September 27, 2011Assignee: Wisconsin Alumni Research FoundationInventors: Weiyuan John Kao, Jing Li, David Lok, Rathna Gundloori
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Patent number: 7754241Abstract: A degradable hydrogel and a method of making a degradable hydrogel is disclosed herein. The method comprises obtaining a hydrophilic polymer having at least two hydroxyl groups, reacting the hydrophilic polymer with a di-functional monomer comprised of an acid halide group and an alkyl halide group to form an intermediate having an ester bond and a terminal alkyl halide group, reacting the terminal alkyl halide group of the intermediate with a metallic salt of a vinyl acid monomer to form a macromonomer comprised of an ester, an alkyl group spacer, and a terminal vinyl group, and polymerizing the macromonomer to form a degradable hydrogel. A method is also disclosed for varying the degradation rate of the hydrogel as a function of the chemical composition of the alkyl group spacer in the terminal linkage of the macromonomer.Type: GrantFiled: November 10, 2005Date of Patent: July 13, 2010Inventors: Charles K. Webb, Naren R. Vyavahare
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Patent number: 7727969Abstract: The present invention relates to a conjugate that includes a nucleic acid ligand bound to a controlled release polymer system, a pharmaceutical composition that contains the conjugate, and methods of treatment using the conjugate. The controlled release polymer system includes an agent such as a therapeutic, diagnostic, prognostic, or prophylactic agent. The nucleic acid ligand that is bound to the controlled release polymer system, binds selectively to a target, such as a cell surface antigen, and thereby delivers the controlled release polymer system to the target.Type: GrantFiled: June 6, 2003Date of Patent: June 1, 2010Assignee: Massachusetts Institute of TechnologyInventors: Omid C. Farokhzad, Sang Yong Jon, Robert S. Langer
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Patent number: 7723086Abstract: An apparatus for encapsulating cells is disclosed. According to one embodiment, the apparatus includes an indirect-pumping dispenser for dispensing a cell suspension into an encapsulation solution through an outlet of the dispenser. The apparatus also includes a dipping mechanism that is attachable to the outlet of the dispenser. The dipping mechanism is adapted to dip the dispenser outlet in the encapsulation solution to allow the cell suspension dispensed thereat to come into contact with the encapsulation solution.Type: GrantFiled: June 16, 2004Date of Patent: May 25, 2010Assignee: Agency for Science, Technology + ResearchInventors: Hanry Yu, Hai Ting Ho, Jing Zhang
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Patent number: 7615593Abstract: Disclosed are hydrogels wherein a polymer matrix is modified to contain a bifunctional poly(alkylene glycol) molecule covalently bonded to the polymer matrix. The hydrogels can be cross-linked using, for example, glutaraldehyde. The hydrogels may also be crosslinked via an interpenetrating network of a photopolymerizable acrylates. The hydrogels may also be modified to have pharmacologically-active agents covalently bonded to the poly(alkylene glycol) molecules or entrained within the hydrogel. Living cells may also be entrained within the hydrogels.Type: GrantFiled: April 23, 2002Date of Patent: November 10, 2009Assignee: Wisconsin Alumni Research FoundationInventors: Weiyun John Kao, Jing Li, David Lok, Rathna Gundloori
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Patent number: 7544496Abstract: The subject invention concerns a composite comprising an organic fluid-swellable, fibrous matrix, such as collagen, and a mineral phase, such as calcium carbonate or phosphate mineral phase, for use as a biomimetic of bone. In another aspect, the subject invention concerns a process for making a composite involving the inclusion of acidic polymers to a supersaturated mineralizing solution, in order to induce an amorphous liquid-phase precursor to the inorganic mineral, which is then absorbed (pulled by capillary action) into the organic matrix. Advantageously, once solidified, a high mineral content can be achieved, with the inorganic mineral crystals embedded within the collagen fibers (intrafibrillarly) and oriented such that they are aligned along the long axes of the fibers of the organic matrix, thereby closely mimicking the natural structure of bone.Type: GrantFiled: May 12, 2006Date of Patent: June 9, 2009Assignee: University of Florida Research Foundation, Inc.Inventors: Laurie B. Gower, Matthew J. Olszta, Elliot P. Douglas, Sivakumar Munisamy, Donna L. Wheeler
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Patent number: 7514249Abstract: The subject invention concerns a composite comprising an organic fluid-swellable, fibrous matrix, such as collagen, and a mineral phase, such as calcium carbonate or phosphate mineral phase, for use as a biomimetic of bone. In another aspect, the subject invention concerns a process for making a composite involving the inclusion of acidic polymers to a supersaturated mineralizing solution, in order to induce an amorphous liquid-phase precursor to the inorganic mineral, which is then absorbed (pulled by capillary action) into the organic matrix. Advantageously, once solidified, a high mineral content can be achieved, with the inorganic mineral crystals embedded within the collagen fibers (intrafibrillarly) and oriented such that they are aligned along the long axes of the fibers of the organic matrix, thereby closely mimicking the natural structure of bone.Type: GrantFiled: October 22, 2003Date of Patent: April 7, 2009Assignee: The University of Florida Research Foundation, Inc.Inventors: Laurie B. Gower, Matthew J. Olszta, Elliot P. Douglas, Sivakumar Munisamy, Donna L. Wheeler
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Patent number: 7514248Abstract: The subject invention concerns a composite comprising an organic fluid-swellable matrix, such as collagen, and mineral phase, such as calcium carbonate or phosphate mineral phase, for use as a biomimetic of bone. In another aspect, the subject invention concerns a process for making a composite involving the inclusion of acidic polymers to a supersaturated mineralizing solution, in order to induce an amorphous liquid-phase precursor to the inorganic mineral, which is then absorbed (pulled by capillary action) into the interstices of the organic matrix, and subsequently mineralizes via solidification and crystallization of the precursor phase. The present invention further concerns a method of treating a patient suffering from a bone defect by applying a biomimetic composite to the bone defect site.Type: GrantFiled: April 18, 2003Date of Patent: April 7, 2009Assignee: University of Florida Research Foundation, Inc.Inventors: Laurie B. Gower, Matthew J. Olszta, Elliot P. Douglas, Sivakumar Munisamy, Donna L. Wheeler
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Patent number: 7153519Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules.Type: GrantFiled: June 25, 2003Date of Patent: December 26, 2006Assignee: Board of Regents, The University of Texas SystemInventors: Jeffrey A. Hubbell, Chandrashekhar P. Pathak, Amarpreet S. Sawhney, Neil P. Desai, Jennifer L. Hill, Syed F. A. Hossainy
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Patent number: 6872576Abstract: The invention relates to an immunoassays, binding assays, solid phase substrates (12) and other devices with an antigen or antibody or ligand or receptor (11) embedded into a solid phase substrate (12). The antigen or antibody is mixed with a molten thermoplastic and formed into the solid phase substrate (12).Type: GrantFiled: March 17, 2000Date of Patent: March 29, 2005Assignee: Embedded Concepts, LLCInventor: John A. McIntyre
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Patent number: 6685957Abstract: A fibrous polymer implant loaded with one or more bioactive agents is prepared using a wet spinning technique. Preferably, an aqueous solution of bioactive agent is added to a solution of amphiphilic block copolymer containing hydrophilic blocks such as polyalkylene glycol and hydrophobic blocks such as an aromatic ester dissolved in a first solvent immiscible with water to form an emulsion. The emulsion is injected through a nozzle into a second solvent miscible with the first solvent in which the copolymer is essentially insoluble to form a solid copolymer fiber loaded with the bioactive agent. The fiber is shaped into an implant. Water content of the aqueous solution of bioactive agent affects rate of release of the bioactive agent in vivo. Bioactive agents include peptides, oligopeptides, polypeptides and proteins. The implant may be used as a carrier for controlled drug release or as a scaffold for tissue engineering.Type: GrantFiled: September 29, 2000Date of Patent: February 3, 2004Assignee: Chienna B.V.Inventors: Jeroen Mattijs Bezemer, Clemens Antoni van Blitterswijk, Jan Feijen, Dirk Wybe Grijpma
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Patent number: 6680184Abstract: A temperature-stable droplet is provided containing a temperature-stable hydrocolloid membrane. The hydrocolloid membrane encapsulates a liquid that contains at least one enzyme, a cell, a biological agent, a pharmaceutical agent, an immunological agent, or mixtures thereof, and at least one of a locust bean gum, a natural thickening agent, a guar, polyvinylpyrrolidone, Konjac mannan, methylcellulose, hydroxymethylcellulose, calcium gluconate, glucomannan, or mixtures thereof. Preferably, the hydrocolloid membrane comprises at least one of methoxy pectin, Konjac mannan, sodium alginate, or mixtures thereof, and at least one of a locust bean gum, methylcellulose, hydroxymethylcellulose, glucomannan, or mixtures thereof. The hydrocolloid membrane encapsulating the liquid is a thickness capable of holding the liquid without bursting through a temperature range of about −20° C. to about 90° C.Type: GrantFiled: September 29, 1999Date of Patent: January 20, 2004Assignee: Yissum Research & Development Co. of Hebrew UniversityInventor: Amos Nussinovitch
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Patent number: 6632446Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, and coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules.Type: GrantFiled: October 23, 2000Date of Patent: October 14, 2003Assignee: The Board of Regents, University of Texas SystemInventors: Jeffrey A. Hubbell, Chandrashekhar P. Pathak, Amarpreet S. Sawhney, Neil P. Desai, Jennifer L. Hill, Syed F. A. Hossainy
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Patent number: 6616946Abstract: Polymeric hollow particles for delivery of an agent are provided that change permeability in response to a change in an external stimulus such as pH, temperature, light, ionic strength, electric field, magnetic field and/or solvent composition. The particles can have a shell formed of an amphiphilic triblock ABA or BAB copolymer, where A is a hydrophilic block and B is a hydrophobic block. Low permeability particles with a reversibly permeable shell expand and increase permeability in response to a stimulus so that an active agent such as a therapeutic, prophylactic or diagnostic agent can be introduced. Removing the stimulus allows the particles to return to a low permeability state to form particles loaded with the active agent. Surfaces of the particles can be modified with specific ligands that allow the particles to be directed to a specific target via molecular recognition.Type: GrantFiled: November 15, 2000Date of Patent: September 9, 2003Assignee: BioCure, Inc.Inventors: Wolfgang Meier, Marc Sauer
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Patent number: 6565842Abstract: 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: GrantFiled: June 7, 1995Date of Patent: May 20, 2003Assignee: American Bioscience, Inc.Inventors: Soebianto A. Sojomihardjo, Neil P. Desai, Paul A. Sandford, Patrick Soon-Shiong, Shubhi Nagrani
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Publication number: 20030008971Abstract: A hydrogel forming system which comprises a hydrophobic macromer with unsaturated group terminated ends and a hydrophilic polymer which is a polysaccharide containing hydroxy groups which are reacted with unsaturated group introducing compound, is convertible by free radical polymerization to form a hydrogel containing a three dimensional crosslinked polymer network containing hydrophobic and hydrophilic components. Agent can be entrapped in the polymer network, e.g., drugs, macromolecules or synthetic or natural polymers, for controlled release therefrom In one embodiment, a vascular stent is coated with hydrogel with therapeutic agent entrapped therein.Type: ApplicationFiled: May 13, 2002Publication date: January 9, 2003Inventors: Chee-Youb Won, Yeli Zhang, Chih-Chang Chu
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Patent number: 6465001Abstract: Water soluble macromers are modified by addition of free radical polymerizable groups, such as those containing a carbon-carbon double or triple bond, which can be polymerized under mild conditions to encapsulate tissues, cells, or biologically active materials. The polymeric materials are particularly useful as tissue adhesives, coatings for tissue lumens including blood vessels, coatings for cells such as islets of Langerhans, and coatings, plugs, supports or substrates for contact with biological materials such as the body, and as drug delivery devices for biologically active molecules. A medical condition at a localized site is treated by applying a polymerization initiator and then applying a substantially water-soluble, degradable macromer of at least 200 mw and having at least two crosslinkable substituents, and polymerizing the macromer to form a crosslinked polymeric material at the site.Type: GrantFiled: March 3, 1998Date of Patent: October 15, 2002Assignee: Board of Regents, The University of Texas SystemsInventors: Jeffrey A. Hubbell, Chandrashekhar P. Pathak, Amarpreet Sawhney, Neil Desai, Syed Hossainy, Jennifer L. Hill-West
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Patent number: 6444261Abstract: A particle resistant to storage of at least one first and at least one second component, wherein said second component of at least one crosslinkable polymer as a shell at least partially envelops and/or encloses said first component as a core and said first component has at least one ascertainable property, obtainable by reacting said first component with the crosslinkable polymer and subsequently reacting the formed product with a crosslinking agent such that the first component with resistance to storage remains within the second component.Type: GrantFiled: July 20, 1998Date of Patent: September 3, 2002Assignee: Abion Beteiligungs-und Verwaltungsgesellschaft mbHInventors: Dmitri Plaksine, Elena Gromakovskaia, Christoph Erhardt
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Publication number: 20020071908Abstract: A particle resistant to storage of at least one first and at least one second component, whereinType: ApplicationFiled: July 20, 1998Publication date: June 13, 2002Inventors: DMITRI PLAKSINE, ELENA GROMAKOVSKAIA, CHRISTOPH ERHARDT
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Patent number: 6399750Abstract: A separation medium having a base matrix and matrix-bound groups which exhibit recombinant Protein A containing a cysteine. The groups are of formula: —B—X—rProtein A-cys where B is a bridge which binds to the base matrix and X includes a heteroatom N or S from rProtein A-cys. In a preferred embodiment X is a thioether sulphur and/or a secondary amine (—NH—). An alternative embodiment features a variant of Protein A in which the C-terminal residue is cysteine.Type: GrantFiled: June 9, 1997Date of Patent: June 4, 2002Assignee: Pharmacia Biotech ABInventor: Ingemar Johansson
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Patent number: 6384188Abstract: Substance which bind with high affinity to endotoxin (lipopolysaccharide [LPS]), and which are useful for the prevention or treatment of, for example, Gram-negative and Gram-positive bacterial sepsis, and for the treatment of bacterial and fungal infections as well as for neutralizing effects associated with heparin. The substances are LPS-binding peptides comprising an LPS-binding domain. DNA sequences encoding peptides, recombinant microorganisms containing the DNA, pharmaceutical compositions containing the peptides of the invention, and diagnostic kits. Methods for the detection and removal of bacterial LPS from solutions.Type: GrantFiled: June 7, 1995Date of Patent: May 7, 2002Assignee: Dana-Farber Cancer Institute, Inc.Inventors: Adolf Hoess, Robert C. Liddington, George R. Siber
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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: 6306959Abstract: Novel polymer-supported quenching reagents of Formula (I): P-L-Q, wherein P is a polymer of low chemical reactivity which is soluble or insoluble; Q is one or more quenching reagents, or an acid or base addition salts thereof, that are capable of selective covalent reaction with unwanted byproducts, or excess reagents; and L is one or more chemically robust linkers that join P and Q; are described, as well as methods for their preparation and methods for their use in the rapid purification of synthetic intermediates and products in organic synthesis, combinatorial chemistry and automated organic synthesis.Type: GrantFiled: October 15, 1998Date of Patent: October 23, 2001Assignee: Warner Lambert CompanyInventors: Gary L. Bolton, Richard J. Booth, Mark W. Creswell, John C. Hodges, Joseph S. Warmus, Michael W. Wilson
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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: 6204256Abstract: A cyclodextrin derivative, wherein at least 60 percent of the free hydroxy groups of said cyclodextrin are acylated with acyl groups where at least one of said acyl groups comprise a free carboxylic group.Type: GrantFiled: April 8, 1999Date of Patent: March 20, 2001Assignee: PolymedInventors: Shalaby W. Shalaby, Joel Thomas Corbett
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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: 6096825Abstract: There are electrically conductive, electroactive functionalized conjugated polymers having formula (I): ##STR1## These electrically conducive, electroactive conjugated polymers may be covalently bonded to a first biological molecule or antiligand. Polymers bonded to a first biological molecule or antiligand may be used to form an electrode and may be used to assay for, detect and/or extract a second biological molecule or ligand.Type: GrantFiled: February 6, 1996Date of Patent: August 1, 2000Assignee: Bio MerieuxInventor: Francis Garnier
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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: 6020175Abstract: Multiple layered functional thin films fixed on a solid support are provided which comprise multiple layers of functional molecules (such as enzymes and other proteins, pigments and dyes) admixed with polymer ions in combination with multiple layers of polymer ions without the functional molecules. The films are prepared by immersing a solid support having an electric charge in an admixed polymer ion-functional molecule solution having a net electric charge opposite to that of the solid support followed by immersing the solid support in a polymer ion solution having a net electric charge opposite to that of the admixed polymer ion-functional molecule solution, and repeating at least once the immersings of the solid support in the solutions.Type: GrantFiled: September 10, 1997Date of Patent: February 1, 2000Assignee: Japan Science and Technology CorporationInventors: Mitsuhiko Onda, Yuri Lvov, Katsuhiko Ariga, Toyoki Kunitake
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Patent number: 5969040Abstract: Conjugates containing a substance with coagulant activity, such as recombinant Factor IX, non-antigenic polymers, such as poly(ethylene glycol), are disclosed. Also disclosed are methods of forming the novel conjugates of this invention.Type: GrantFiled: December 13, 1996Date of Patent: October 19, 1999Inventors: Terrence W. Hallahan, Carl W. Gilbert
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Patent number: 5968729Abstract: A method is provided using centrifugation to prepare a seal of solidified wax, grease or polymer mix over an aqueous reagent in a reaction container such that the reagent is separated from contact with the atmosphere. The amount of solidified wax, grease or polymer mix is not sufficient when melted to a liquid to separate the reagent from contact with the atmosphere under gravity. A reagent and solidified wax, grease or polymer mix are combined in a container. During centrifugation and heating, the solidified wax, grease or polymer mix melts to a liquid, and centrifuging causes the liquid to form over the reagent a layer that completely separates the reagent from the atmosphere. As centrifugation continues, the liquid is cooled and solidified to form the seal. Additional reagents are preferably added on top of the seal such that when the container is heated and the seal melted the upper and lower reagents mix for reaction.Type: GrantFiled: March 28, 1998Date of Patent: October 19, 1999Inventors: Kenneth M. Kosak, Matthew K. Kosak
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Automated histo-cytochemistry apparatus and encapsulation system for processing biological materials
Patent number: 5965454Abstract: There is disclosed an automated apparatus, reagents and process for immunocytochemical staining of biological materials using ligand pairing. The present invention provides a method for storing a ligand in a macroscopic solid support and releasing the ligand into contact with a biological sample mounted on a surface of a substrate. The process includes providing a macroscopic solid support formed of a solidified matrix material encapsulating a ligand therein with the macroscopic solid support being disintegratable to release the ligand therefrom. The solid support is placed in a first chamber which is in flow communication with a second chamber containing the substrate with the biological sample affixed thereto. The step of disintegrating the macroscopic solid support may include heating the macroscopic solid support to liquefy it when the matrix material is gelatin or a wax.Type: GrantFiled: May 5, 1997Date of Patent: October 12, 1999Assignee: Histaggen IncorporatedInventors: A. James Farmilo, Ronald H. Stead -
Patent number: 5948889Abstract: A method for screening compounds for antimicrobial activity is described that utilizes bacterial protein-protein binding in vitro. The method may be performed using immobilized elements and the immobilization may be carried out using a variety of immobilization means (e.g., columns, beads, adsorbents, nitrocellulose paper, etc.) in order to screen large libraries of compounds.Type: GrantFiled: May 21, 1996Date of Patent: September 7, 1999Assignee: Case Western Reserve UniversityInventors: Piet A. J. de Boer, Cynthia A. Hale
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Patent number: 5902799Abstract: Polyionic derivatives of cyclodextrins and methods for preparing these derivatives are provided in which a polyionic derivative of cyclodextrin is combined with a growth factor, preferably a heparin binding growth factor. These compositions are of low solubility and are applied directly to the location of a wound. By virtue of the low solubility, the compositions remain in place at the site of application and slowly release growth factor. In an alternative embodiment, the cyclodextrin derivatives are administered in the absence of growth factor and are used to absorb growth factor present in the body at the location of the wound in order to prevent overstimulation of the wound response.Type: GrantFiled: August 5, 1997Date of Patent: May 11, 1999Assignee: The Trustees of the University of PennsylvaniaInventors: Howard C. Herrmann, Elliot Barnathan, Paul B. Weisz
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Patent number: 5807757Abstract: A method is provided for preparing polyphosphazene microspheres wherein the polyphosphazene microspheres are produced by coacervation. A solution containing a polyphosphazene is admixed with a solution containing a salt of a monovalent ion such as a salt of a Group I element (for example, NaCl) to form a dispersion containing polyphosphazene coacervate microdroplets. The dispersion then is admixed with a solution containing a salt of a multivalent ion, such as a salt of a Group II element (for example, CaCl.sub.2) to form a suspension of polyphosphazene microspheres. The polyphosphazene microspheres then are recovered from the suspension. Such method enables one to obtain high yields of microspheres having a controlled size distribution. Polyphosphazene microspheres containing biological material can be produced by providing a biological material in the polyphosphazene solution that is mixed with the solution containing a salt of a monovalent ion.Type: GrantFiled: July 2, 1996Date of Patent: September 15, 1998Assignee: Virus Research Institute, Inc.Inventors: Alexander K. Andrianov, Jianping Chen
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Patent number: 5723588Abstract: Thermoplastics interdispersed with a variety of functional thermostable polypeptides, including proteins, and methods of making such thermoplastics are provided. The disclosure demonstrates that certain polypeptides can retain functional activity through exposure to plastic thermomolding. The polypeptides are exposed to the heating and molding/extrusion/casting process and are hence present on the formed plastic surface and at a depth below the plastic surface. The polypeptides contained in the disclosed compositions retain functional properties or binding specificities through the heating and molding/extrusion/casting processes. Preferred thermostable polypeptides used in the disclosed compositions include silk-like protein polymers, particularly ProNectin.RTM.F. The disclosed methods and compositions find use in many applications where plastics containing functional thermostable polypeptides are desired, in particular, cell cultureware.Type: GrantFiled: July 9, 1993Date of Patent: March 3, 1998Assignee: Protein Polymer Technologies, Inc.Inventors: David A. Donofrio, Erwin R. Stedronsky
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Patent number: 5700783Abstract: A method for treating urinary incontinence consisting of injecting human fibrin glue at or near the bladder neck until the urethral outflow resistance is restored. Human fibrin glue is the reaction product of human fibrinogen and thrombin in the presence of calcium chloride as catalyst.Type: GrantFiled: April 24, 1995Date of Patent: December 23, 1997Assignee: Angelo PintoInventor: Angelo Pinto
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Patent number: 5656450Abstract: A latent growth factor such as transforming growth factor beta (TGF.beta.) is converted to active form by matrix vesicles or an extract from matrix vesicles. The matrix vesicles may be stimulated with a Regulator of Enhancing Factor (REF) such as 1,25-dihydroxy vitamin D (1,25-(OH).sub.2 D.sub.3) or steroid hormones which may be intercalated into the vesicle membrane. The latent growth factor may be activated in culturing cells such as chondrocytes that have been pretreated with 24,25-(OH).sub.2 D.sub.3 to activate cell differentiation, or in healing of bone or cartilage defects, and activation can be carried out in vivo or in vitro. Biodegradable polymeric implants may be prepared containing latent growth factor, REF, matrix vesicle or matrix vesicle extract.Type: GrantFiled: May 27, 1994Date of Patent: August 12, 1997Assignee: Board of Regents, the University of Texas SystemInventors: Barbara D. Boyan, Zvi Schwartz, Lynda F. Bonewald
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Patent number: 5650489Abstract: The instant invention provides a library of bio-oligomers of defined size and known composition, in which the library contains all of the possible sequences of the bio-oligomers, and a method of synthesis thereof. The bio-oligomers of the library may be peptides, nucleic acids, or a combination of the foregoing. The instant invention also provides methods to identify bio-oligomers from a library that demonstrate desired characteristics such as binding, bioactivity and catalytic activity. Thus the instant invention provides a unique and powerful method to identify a useful bio-oligomer sequences from a library more quickly than current state-of-the-art technology allows. Effector molecules for use in treatment or diagnosis of disease are also provided.Type: GrantFiled: June 19, 1991Date of Patent: July 22, 1997Assignee: The Arizona Board of RegentsInventors: Kit Sang Lam, Sydney E. Salmon
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Patent number: 5643764Abstract: A reagent such as a heat resistant enzyme is entrapped in a material such as wax or a liposome that releases the reagent when heated so the reagent is available for reaction. In a preferred embodiment, wax beads containing the reagent are prepared by injecting the reagent into beads of molten wax and cooling to solidify the wax. In another embodiment, droplets of a solution of the reagent are dropped through a layer of molten wax to coat the droplets with the wax and the coated droplets are cooled to solidify the wax. The entrapped reagents have application in nucleic acid hybridizations, polymerase chain reactions (PCR), reverse transcriptase reactions (RTR), nucleic acid sequencing, and product generating reactions such as colorimetic, fluorometric and chemiluminescent enzyme labeled immunoassays.Type: GrantFiled: March 1, 1995Date of Patent: July 1, 1997Inventors: Kenneth M. Kosak, Matthew K. Kosak
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Patent number: 5643773Abstract: Elongated seamless capsules containing biological material are prepared by a method in which a coagulant, which includes a cell suspension or other biological material, and a polymeric casting solution are extruded through a common extrusion port having at least two concentric bores, such that the coagulant is extruded through an inner bore and the polymeric casting solution is extruded through an outer bore. Extrusion of the coagulant is initiated subsequent to initiating delivery of the casting solution to form a capsule having a curved and smooth leading edge shape. Delivery of the coagulant is then shut off, and extrusion of the casting solution is terminated either immediately or after some predetermined time. This procedure can be modified to form in the capsule a coaxial rod that is connected to one end but not the other end of the capsule.Type: GrantFiled: April 27, 1995Date of Patent: July 1, 1997Assignee: Brown University Research FoundationInventors: Patrick Aebischer, John F. Mills, Lars Wahlberg, Edward J. Doherty, Patrick A. Tresco
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Patent number: 5563056Abstract: A chemical specie is immobilized in a three dimensional, crosslinked matrix by bringing together in covalent bonding proximity a desired chemical specie and a polymeric coupling compound such as a photoderivatized polymer having at least two latent photochemical reactive groups per molecule, each latent reactive group being capable when activated of covalently bonding to another coupling compound molecule or to the chemical specie. The chemical specie may be a protein, carbohydrate, nucleic acid or lipid, and desirably is free of latent reactive groups that are activated upon activation of the latent reactive groups of the coupling compound. The latent reactive groups are simultaneously activated to cause formation via covalent bonding of a three-dimensional molecular network in which molecules of the chemical specie are covalently bonded to molecules of the coupling compound, and molecules of the coupling compound are covalently bonded to each other.Type: GrantFiled: February 27, 1995Date of Patent: October 8, 1996Assignee: BSI CorporationInventors: Dale G. Swan, Mark W. Josephson, Melvin J. Swanson
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Patent number: 5550044Abstract: Droplets of molten wax or waxy polymer containing a reagent are dropped onto the surface of liquid nitrogen, the droplets remain on the surface until solidified and the droplets are removed from the surface before they sink into the liquid nitrogen to provide beads containing the reagent. The reagent can be any material that can be entrapped in the beads and does not undergo excessive inactivation when the beads are melted by heating to release the reagent. Examples of reagents are heat resistant enzymes, enzyme substrates, metal salts, oligonucleotides, inclusion compounds, surfactants, emulsifiers, antioxidants, stabilizers, drugs, antibiotics, antibodies and antigens. An apparatus for producing the beads contains a plurality of channels through which liquid nitrogen flows from a reservoir. Each channel passes under a dispenser tip from which droplets are formed and released onto the surface of flowing liquid nitrogen.Type: GrantFiled: June 10, 1994Date of Patent: August 27, 1996Inventors: Kenneth M. Kosak, Matthew K. Kosak
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Patent number: 5418154Abstract: Elongated seamless capsules containing biological material are prepared by a method in which a coagulant, which includes a cell suspension or other biologically active factor, and a polymeric casting solution are extruded through a common extrusion port having at least two concentric bores, such that the coagulant is extruded through the inner bore and the polymeric casting solution is extruded through the outer bore. The method involves initiating extrusion of the coagulant subsequent to initiating delivery of the casting solution through the respective bores to form a capsule having a curved and smooth leading edge shape. Delivery of the coagulant is then shut off, and extrusion of the casting solution is terminated either immediately or after some predetermined time.Type: GrantFiled: December 24, 1992Date of Patent: May 23, 1995Assignee: Brown University Research FoundationInventors: Patrick Aebischer, John F. Mills, Lars Wahlberg, Edward J. Doherty, Patrick A. Tresco