Patents Represented by Attorney, Agent or Law Firm Ivor R. Elrifi
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Patent number: 5871985Abstract: Vehicles containing cells for implanting in the tissue of an individual are prepared having cells dispersed in a particulate, essentially non cross-linked chitosan core matrix that is enclosed within a semipermeable membrane. The cells are entrapped between chitosan particles of the core matrix and there is essentially no interfacial cross-linking between the core matrix and the membrane. The core matrix provides a physical support for viable cells within the vehicle such that the cells are evenly dispersed throughout the core matrix so as to allow their maintenance, growth, proliferation and differentiation. The vehicle can be prepared by mixing viable cells with a solution of chitosan, encapsulating the resultant mixture in a semipermeable membrane and causing the chitosan to precipitate such as by changing the pH to form the core matrix. Alternatively, the chitosan is precipitated to form the core matrix containing cells and then the core matrix is encapsulated in a semipermeable membrane.Type: GrantFiled: August 22, 1994Date of Patent: February 16, 1999Assignee: Brown University Research FoundationInventors: Patrick Aebischer, Beth A. Zielinski
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Patent number: 5871487Abstract: A microdrive apparatus useful in human stereotactic surgery is disclosed. Such apparatus permits safe and accurate placement of a surgical instrument, such as a cannula, into a portion of the central nervous system, e.g. the brain and spinal cord, of a patient by simple mechanical operation.Type: GrantFiled: March 10, 1997Date of Patent: February 16, 1999Assignee: CytoTherpeutics, Inc.Inventors: Nicholas Warner, Moses Goddard, John Mills
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Patent number: 5871472Abstract: Methods are disclosed for the alleviation of movement disorders via the implantation of static devices which focally release neuroinhibitory compounds to preselected brain areas. Pathological conditions to be treated by these methods include parkinsonian movement disorders, Huntington's chorea, and epileptiform seizure activity. In the treatment of parkinsonism, target areas implantation include the subthalamic nucleus, the globus pallidus internus, and the substantia nigra pars reticulata. In the treatment of epilepsy, implants may be placed in an epileptogenic focus area of neural over-activity. The devices may be polymeric implants that release neuroinhibitory compounds such as GABA, GABA agonists, GABA potentiators, action potential blockers and voltage dependent calcium channel blockers, and glutamate antagonists. Alternatively, the devices may contain living cells which secrete neuroinhibitory compounds.Type: GrantFiled: July 13, 1992Date of Patent: February 16, 1999Assignee: Brown University Research FoundationInventors: Patrick Aebischer, Patrick A. Tresco
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Patent number: 5853385Abstract: This invention relates to implantation of encapsulated PC12 cells capable of slowing or preventing the degenerative processes of Parkinson's disease by releasing factors in addition to dopamine into individuals suffering from the disease. This restorative effect continues even after the encapsulated cells are removed from the patient's brain.Type: GrantFiled: August 26, 1994Date of Patent: December 29, 1998Assignee: CytoTherapeutics, Inc.Inventors: Dwaine F. Emerich, Patrick Aebischer, Jeffrey H. Kordower
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Patent number: 5853717Abstract: This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination.Type: GrantFiled: May 23, 1995Date of Patent: December 29, 1998Assignee: CytoTherapeutics, Inc.Inventors: Malcolm Schinstine, Molly S. Shoichet, Frank T. Gentile, Joseph P. Hammang, Laura M. Holland, Brian M. Cain, Edward J. Doherty, Shelley R. Winn, Patrick Aebischer
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Patent number: 5844077Abstract: A method for producing analgesia or for neuroprotection in a mammal comprising administering a therapeutically effective amount of a conantokin to the mammal.Type: GrantFiled: April 28, 1997Date of Patent: December 1, 1998Assignee: CytoTherapeutics, Inc.Inventor: Joel Saydoff
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Patent number: 5840576Abstract: This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination.Type: GrantFiled: May 23, 1995Date of Patent: November 24, 1998Assignee: CytoTherapeutics, Inc.Inventors: Malcolm Schinstine, Molly S. Shoichet, Frank T. Gentile, Joseph P. Hammang, Laura M. Holland, Brian M. Cain, Edward J. Doherty, Shelley R. Winn, Patrick Aebischer
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Patent number: 5837234Abstract: A bioartificial organ for implanting to provide a therapeutic effect is prepared containing a core of living cells encapsulated in a foam-like membrane having three regions: a dense, fine-pored, permselective inner region, a middle region that lacks macrovoids and a fine-pored outer region. The membrane has a molecular weight cutoff that permits passage to nutrients to the cells but not passage of the cells. Preferably, the membrane is made of polyether sulfone, pores range in size between 0.02 .mu.m and 2.0 .mu.m and have polyhedrally symmetric boundaries and are arranged asymmetrically from one surface to the other. The membrane has an asymmetry factor AF relative to the maximum pore diameter of 0.01 to 2.0 and a ratio of the maximum mean free path length to the diameter of the largest pore of greater than 3. The membrane can be hydrophobic or hydrophilic. The bioartificial organ is formed by coextrusion or by stepwise assembly by forming the cell core and then applying the membrane.Type: GrantFiled: June 7, 1995Date of Patent: November 17, 1998Assignee: CytoTherapeutics, Inc.Inventors: Frank T. Gentile, Shelley R. Winn, Michael Lysaght, Ulrich Baurmeister, Friedbert Wechs, Henning Rottger
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Patent number: 5833979Abstract: This invention relates to methods and compositions of controlling cell distribution within a bioartificial organ by exposing the cells to a treatment that inhibits cell proliferation, promotes cell differentiation, or affects cell attachment to a growth surface within the bioartificial organ. Such treatments include (1) genetically manipulating cells, (2) exposing the cells to a proliferation-inhibiting compound or a differentiation-inducing compound or removing the cells from exposure to a proliferation-stimulating compound or a differentiation-inhibiting compound; exposing the cells to irradiation, and (3) modifying a growth surface of the BAO with ECM molecules, molecules affecting cell proliferation or adhesion, or an inert scaffold, or a combination thereof. These treatments may be used in combination.Type: GrantFiled: May 23, 1995Date of Patent: November 10, 1998Assignee: CytoTherapeutics, Inc.Inventors: Malcolm Schinstine, Molly S. Shoichet, Frank T. Gentile, Joseph P. Hammang, Laura M. Holland, Brian M. Cain, Edward J. Doherty, Shelley R. Winn, Patrick Aebischer
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Patent number: 5834029Abstract: A bioartificial three-dimensional hydrogel extracellular matrix derivatized with a cell adhesive peptide fragment is provided for use in tissue regeneration or replacement. The choice of adhesive peptide fragment depends on the desired target cell type. Cartilage or tendon can be regenerated by implanting a matrix containing adhesive peptide fragments that favor chondrocyte invasion. The matrix can be pre-seeded with cells, and tissue can be reconstituted in vitro and then implanted. A cell-seeded matrix can be encapsulated in a semi-permeable membrane to form a bioartificial organ. An agarose hydrogel matrix having an agarose concentration of 0.5-1.25% (w/v) and an average gel pore radius between 120 nm and 290 nm is preferred. The peptide fragment preferably contains the sequence, ArgGlyAsp or TyrIleGlySerArg or IleLysValAlaVal, and is covalently immobilized to the matrix.Type: GrantFiled: July 20, 1994Date of Patent: November 10, 1998Assignee: CytoTherapeutics, Inc.Inventors: Ravi Bellamkonda, John P. Ranieri, Patrick Aebischer
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Patent number: 5798113Abstract: A method of providing a biologically active molecule or metabolic or immunologic function to a patient, comprising implanting into the body of the patient at least one immunoisolatory vehicle comprising a core comprising a volume in excess of 1 .mu.l and at least about 10.sup.4 living cells dispersed in a biocompatible matrix formed of a hydrogel or extracellular matrix components, said cells being capable of secreting a biologically active product or of providing a metabolic or immunologic function to the patient; and an external jacket surrounding said core, said jacket being formed from a thermoplastic or hydrogel, said jacket being free of said cells projecting externally therefrom, said jacket being biocompatible and having a molecular weight cutoff permitting passage of molecules between the patient and the core through said jacket to provide said biologically active product of function.Type: GrantFiled: May 24, 1995Date of Patent: August 25, 1998Assignee: Brown University Research FoundationInventors: Keith E. Dionne, Dwaine F. Emerich, Diane Hoffman, Paul R. Sanberg, Lisa Christenson, Orion D. Hegre, David W. Scharp, Paul E. Lacy, Patrick Aebischer, Alfred V. Vasooncellos, Michael J. Lysaght, Frank T. Gentile
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Patent number: 5773255Abstract: A line of .beta. cells is described which is capable of maintaining high levels of insulin secretion in culture. Such cells are useful in the treatment of diabetes, for example, by encapsulation of the cells in an insulin-permeable membrane device, followed by implantation into a diabetes patient.Type: GrantFiled: June 5, 1995Date of Patent: June 30, 1998Assignee: CytoTherapeutics, Inc.Inventors: Megan E. Laurance, David Knaack, Deborah M. Fiore, Orion D. Hegre
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Patent number: 5738673Abstract: A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33).Type: GrantFiled: June 7, 1995Date of Patent: April 14, 1998Assignee: Brown University Research FoundationInventors: John F. Mills, Edward J. Doherty, Tyrone F. Hazlett, Keith E. Dionne, Nicholas F. Warner, Brian M. Cain, David H. Rein
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Patent number: 5720969Abstract: A permselective graft polymer is disclosed that is formed by converting into intermediate reactive sites a portion of the cyano groups of a backbone polymer and grafting polyalkylene oxide polymer chains to the backbone polymer through the reactive sites. Either the backbone polymer of a polymer resin or a permselective polymer membrane can be grafted. When a resin is used, it is formed into a permselective polymer membrane using known methods. The resulting permselective membrane can be formed into hollow fibers or flat sheets for the encapsulation of living cells. The encapsulated cells are then implanted into a patient in need of the biologically-active factors produced by the cells. The permselective graft polymer membrane exhibits good molecular diffusion with minimal protein adsorption.Type: GrantFiled: January 16, 1996Date of Patent: February 24, 1998Assignee: CytoTherapeutics, Inc.Inventors: Frank Gentile, Molly Shoichet, Milton Harris
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Patent number: 5713887Abstract: A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33).Type: GrantFiled: June 6, 1995Date of Patent: February 3, 1998Assignee: Brown University Research FoundationInventors: John F. Mills, Edward J. Doherty, Tyrone F. Hazlett, Keith E. Dionne, Nicholas F. Warner, Brian M. Cain, David H. Rein
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Patent number: 5712159Abstract: A cell culture of correctly regulated .beta.-cells having enhanced secretion of insulin is described. A method of selecting such correctly regulated .beta.-cells is also described comprising the following steps:(a) providing a population of cells comprising .beta.-cells in which increased intracellular concentrations of calcium ions is correlated with the extracellular presence of glucose;(b) exposing the population to a vital calcium-activated labelling agent;(c) exposing the population to glucose in a concentration sufficient to result in secretion of the insulin; and(d) selecting from the population, cells which exhibit a higher level of intracellular free calcium or insulin secretion when exposed to said concentration.Type: GrantFiled: June 5, 1995Date of Patent: January 27, 1998Assignee: Brown University Research FoundationInventors: Megan E. Laurance, David Knaack, Deborah M. Fiore, Orion D. Hegre
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Patent number: 5656469Abstract: A method for encapsulating biological substances in biocompatible microcapsules is disclosed, the method comprising:(a) maintaining a coating-forming liquid film sheet transverse to a vertical plane, said sheet comprising an organic polymerizable monomer liquid,(b) causing droplets comprising biological substances in an aqueous medium to fall downwardly through said liquid film sheet to form microcapsules comprising cores of said droplets coated by said film,(c) permitting said microcapsules to fall downwardly from said liquid film sheet, and(d) polymerizing said liquid film coatings during descent of said microcapsules below said sheet to form a permeable polymer coating of a sufficient structural integrity so that said microcapsules are self-supporting.Type: GrantFiled: August 14, 1995Date of Patent: August 12, 1997Assignee: Brown University Research FoundationInventors: Patrick A. Tresco, John F. Mills
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Patent number: 5653687Abstract: A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33).Type: GrantFiled: June 6, 1995Date of Patent: August 5, 1997Assignee: Brown University Research FoundationInventors: John F. Mills, Edward J. Doherty, Tyrone F. Hazlett, Keith E. Dionne, Nicholas F. Warner, Brian M. Cain, David H. Rein
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Patent number: 5653688Abstract: A sealed, implantable, encapsulation device (20) for diffusing a biologically active product or function to an individual which includes a substantially non-porous fitting (32) including an inner surface (33) defining an access port (34). A permselective, porous, membrane (21), having an interior surface (22), cooperates with the fitting inner surface (33) to form a storage cavity (23) therebetween. The membrane interior surface (22) is in substantially cell-tight dry sealing engagement with fitting (32) to seal cavity (23). Living cells (24) are disposed in the cavity (23) which are capable of secreting the biologically active product to an individual. The membrane (21) is of a material capable of permitting the passage of substances between the individual and cells required to provide the biological product or function. A plug member (35) is positioned in the access port (34) and seated in cell-tight sealing engagement with the fitting inner surface (33).Type: GrantFiled: June 6, 1995Date of Patent: August 5, 1997Assignee: Brown University Research FoundationInventors: John F. Mills, Edward J. Doherty, Tyrone F. Hazlett, Keith E. Dionne, Nicholas F. Warner, Brian M. Cain, David H. Rein
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Patent number: D355676Type: GrantFiled: January 18, 1994Date of Patent: February 21, 1995Assignee: King Products LimitedInventor: Donald H. Wilson