Patents Examined by Anne-Marie Falk
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Patent number: 6995299Abstract: The present invention relates to the preparation of non-human animals having chimeric livers, whereby some or substantially all of the hepatocytes present are human hepatocytes. It is based, at least in part, on the discovery that rats, tolerized in utero against human hepatocytes, were found to serve as long-term hosts for human hepatocytes introduced post-natally, and the introduced hepatocytes maintained their differentiated phenotype, as evidenced by continued production of human albumin. The present invention further relates to the use of such animals as models of various liver diseases, including viral invention. Such embodiments are based on the discovery that transplanted human hepatocytes in chimeric livers were found to be susceptible to Hepatitis B virus and Hepatitis C virus infection.Type: GrantFiled: August 15, 2001Date of Patent: February 7, 2006Assignee: University of ConnecticutInventors: George Y. Wu, Catherine H. Wu
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Patent number: 6967100Abstract: The present invention relates generally to growth factors and more particularly to growth factors which are capable of stimulating or otherwise facilitating formation of insulin-secreting cells. The identification of these growth factors permits the development of protocols to culture cells in vitro for transplantation into mammalian and in particular human subjects with insulin-dependent type 1 diabetes or related conditions. It is further contemplated that the endogenous expression of growth factors required for the development of insulin-producing cells may be manipulated in vivo, by the appropriate administration of agents including genetic agents capable of regulating the expression of growth factors in pancreatic duct epithelial cells. The growth factors ray also be administered to subjects with type 1 diabetes to stimulate the proliferation and differentiation of pancreatic cells into insulin-secreting cells.Type: GrantFiled: February 16, 2001Date of Patent: November 22, 2005Assignee: The Walter and Eliza Hall Institute of Medical ResearchInventors: Leonard C. Harrison, Fang-Xu Jiang, Edouard Guy Stanley, Leonel Jorge Gonez
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Patent number: 6962688Abstract: Methods for regulation of lipid and cholesterol uptake are described which are based on regulation of the expression or function of the SR-BI HDL receptor. The examples demonstrate that estrogen dramatically downregulates SR-BI under conditions of tremendous upregulation of the LDL-receptor. The examples also demonstrate the upregulation of SR-BI in rat adrenal membranes and other non-placental steroidogenic tissues from animals treated with estrogen, but not in other non-placental non-steroidogenic tissues, including lung, liver, and skin. Examples further demonstrate the uptake of fluorescently labeled HDL into the liver cells of animal, which does not occur when the animals are treated with estrogen. Examples also demonstrate the in vivo effects of SR-BI expression on HDL metabolism, in mice transiently overexpressing hepatic SR-BI following recombinant adenovirus infection. Overexpression of the SR-BI in the hepatic tissue caused a dramatic decrease in cholesterol blood levels.Type: GrantFiled: August 30, 1999Date of Patent: November 8, 2005Assignees: Trustees of the University of Pennsylvania, Massachusetts Institute of TechnologyInventors: Karen Kozarsky, Attilio Rigotti, Monty Krieger
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Patent number: 6962975Abstract: The invention provides prion protein standards for use as reference materials for prion detection. The standard may be species specific, i.e. the standard is comprised of a preparation for detection of a single strain prion or it may be prepared to allow detection of multiple prion strains simultaneously. The invention also provides methods of preparing the prion protein standards using a group of non-human host mammals which have their genome manipulated with respect to genetic material related to a PrP gene such that the mammals are susceptible to infection with a prion which generally only infects an animal which is genetically diverse from the host.Type: GrantFiled: November 17, 1999Date of Patent: November 8, 2005Assignee: The Regents of the University of CaliforniaInventor: Stanley B. Prusiner
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Patent number: 6955802Abstract: Provided are genetically engineered cells comprising a neural stem cell and retroviral expression system in the neural stem cell, which is capable of expressing homeodomain transcription factor Nkx6.1 protein but does not express homeodomain transcription factor Irx3 protein or homeodomain transcription factor Nkx2.2 protein; which is capable of expressing homeodomain transcription factor Nkx6.1 protein and homeodomain transcription factor Irx3 protein; and which is capable of expressing homeodomain transcription factor Nkx2.2 protein or homeodomain transcription factor Nkx2.9 protein. Also provided are methods of generating such genetically engineered motor neurons, V2 neurons, and V3 neurons.Type: GrantFiled: May 11, 2000Date of Patent: October 18, 2005Assignee: The Trustees of Columbia University in the City of New YorkInventors: Thomas M. Jessell, James Briscoe, Johan Ericson
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Patent number: 6953686Abstract: The present invention provides methods for the purification of plasmid DNA that includes removal of host cell impurities, such as endotoxins, RNA, proteins, and chromosomal DNA, from an aqueous solution containing plasmid DNA and methods for separation and purification of supercoiled plasmid DNA from an aqueous solution containing a mixture of supercoiled and nicked or relaxed plasmid DNA using hydrophobic interaction chromatography supports.Type: GrantFiled: May 26, 2000Date of Patent: October 11, 2005Assignee: Cambrex Bio Science Baltimore, Inc.Inventor: Natarajan Ramasubramanyan
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Patent number: 6943277Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising mutations in a stefin homolog gene. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions.Type: GrantFiled: July 11, 2001Date of Patent: September 13, 2005Assignee: Deltagen, Inc.Inventor: Keith D. Allen
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Patent number: 6939540Abstract: The present invention is directed to a method for enhancing bone density or formation. In accordance with the method, a nucleic acid encoding an angiogenic protein is administered to a cell in a region of a bone such that the nucleic acid is expressed to produce the angiogenic protein, whereby bone density or formation is enhanced within the region. Optionally, a nucleic acid encoding an osteogenic protein is administered to a cell within the same region such that the nucleic acid is expressed to produce the osteogenic protein. The method can be employed to produce a bone graft having a cell harboring an exogenous nucleic acid encoding an angiogenic protein and, optionally, a cell harboring a nucleic acid encoding an osteogenic protein. To facilitate the inventive method, the invention also pertains to a recombinant viral vector having a nucleic acid encoding an angiogenic protein and a nucleic acid encoding an osteogenic protein.Type: GrantFiled: July 31, 2000Date of Patent: September 6, 2005Assignees: Cornell Research Foundation, Inc., The Hospital for Special Surgery, GenVec, Inc.Inventors: Ronald G. Crystal, Chisa Hidaka, Oheneba Boachie-Adjei, Bernard A. Rawlins, Imre Kovesdi
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Patent number: 6933150Abstract: The present invention includes methods of performing ex vivo expansion of gene-modified hematopoietic stem cells which are useful for many applications involving bone marrow transplantation and ex vivo gene therapy. The present invention further includes the gene-modified hematopoietic stem cells that are used and produced by such methods. Such gene-modified hematopoietic stem cells can also contain a second heterologous gene. In addition, the present invention also includes methods of engrafting the gene-modified hematopoietic stem cells of the present invention into animals, including for ex vivo gene therapy and for reconstitution of hematopoietic cells in ablated mammals. The present invention also provides a method of isolating stem cells.Type: GrantFiled: May 31, 2000Date of Patent: August 23, 2005Assignee: St. Jude Children's Research HospitalInventors: Brian Sorrentino, Kevin Bunting, John Schuetz, Hiromitsu Nakauchi
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Patent number: 6924413Abstract: This invention provides experimental animals suffering corneal epithelial damages, such as dry eye, and methods of using the same to assay a variety of compounds for evaluating the therapeutic effect on the disease, and medicine selected using the method, wherein the corneal epithelial damage is induced by the steps of: using a water-absorbing material having a physical state selected from powder, solution, gel, jelly and tablet, and contacting the absorbing materials with the ocular cornea to generate a difference in osmotic pressure between the inside and outside of ocular corneal epithelium cells.Type: GrantFiled: January 10, 2002Date of Patent: August 2, 2005Assignee: Biochemical and Pharmacological Laboratories, Inc.Inventor: Iwao Katsuyama
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Patent number: 6897353Abstract: The functional analysis of genes frequently requires the manipulation of large genomic regions. A yeast-bacteria shuttle vector is described, that can be used to clone large regions of DNA by homologous recombination. The important feature of present invention is the presence of the a bacterial replication origin, which allows large DNA insert capacity. The utility of this vector lies in its ability to isolate, manipulate and maintain large fragments in bacteria and yeast, allowing for mutagenesis by yeast genetics and simplified preparation of plasmid DNA in bacteria.Type: GrantFiled: December 4, 2000Date of Patent: May 24, 2005Assignee: Yale UniversityInventors: M. Suzanne Bradshaw, Jacques A. Bollekens, Frank H. Ruddle
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Patent number: 6890909Abstract: A brain-protective agent containing an NF-?B decoy. In brain diseases, the brain can be particularly effectively protected against brain disorders (for example, cerebral vasospasm following a subrachnoidal hemorrhage and apoptosis of the nerve cells following a cerebrovasucular accident or serious head injury) caused by the undesired activation of cytokines or cell adhesion factors which are regulated by NF-?B by administering the brain-protective agent containing an NF-?B decoy, i.e., acompound antadonistic specifically to a nucleic acid to which NF-?B binds.Type: GrantFiled: July 3, 1998Date of Patent: May 10, 2005Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Shigeki Ono, Isao Date
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Patent number: 6858772Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising mutations in the magnesium-dependent protein phosphatase gene. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions.Type: GrantFiled: October 5, 2001Date of Patent: February 22, 2005Assignee: Deltagen, Inc.Inventor: Keith D. Allen
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Patent number: 6855314Abstract: The present invention provides methods of delivering nucleic acids to specific regions, tissues and cell types of the CNS. More particularly the invention provides methods of delivering nucleic acids to cells of the CNS such as cerebellar cells and ependymal cells. The invention also provides methods of delivering nucleic acids to cells of the lung such as alveolar cells using AAV5 vectors and particles.Type: GrantFiled: March 22, 2000Date of Patent: February 15, 2005Assignees: The United States of America as represented by the Department of Health and Human Services, University of Iowa Research FoundationInventors: John A. Chiorini, Robert M. Kotin, Beverly Davidson, Joseph Zabner
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Patent number: 6852529Abstract: The subject invention pertains to nucleic acid constructs for post-transcriptional control of expression of a ploynucleotide encoding a protein in a eukaryotic cell, wherein the constructs include a metabolite responsive instability element such as the glucose-regulated mRNA instability element. The subject invention further pertains to host cells and vectors comprising the nucleic acid constructs of the invention, as well as probes, methods, and kits for detecting metabolite responsive instability elements or mutations thereof.Type: GrantFiled: November 8, 1999Date of Patent: February 8, 2005Assignee: University of South FloridaInventors: Denise R. Cooper, Niketa A. Patel
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Patent number: 6852323Abstract: This invention relates generally to the field of urology. In particular, the invention provides a method for preventing or treating male erectile dysfunction or female sexual arousal disorder, which method comprises administering an effective amount of vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor (bFGF), or a functional derivative or fragment thereof, or a nucleic acid encoding said VEGF, BDNF or bFGF, or functional derivative or fragment thereof, or an agent that enhances production and/or erection or sexual arousal stimulating function of said VEGF or BDNF or bFGF to a mammal, wherein such prevention or treatment is desirable, thereby preventing or treating said male erectile dysfunction or female sexual arousal disorder in said mammal. Combinations, combinatorial methods and kits for preventing or treating male erectile dysfunction or female sexual arousal disorder are also provided.Type: GrantFiled: July 19, 2001Date of Patent: February 8, 2005Assignee: The Regents of the University of CaliforniaInventors: Tom F. Lue, Ching-Shwun Lin, Yuet W. Kan
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Patent number: 6849454Abstract: The present invention pertains to a method for efficiently introducing exogenous genes into stem cells, particularly human stem cells. The method optionally includes the steps of inducing the proliferation of target cells by pre-stimulation with cytokines and/or growth factors, followed by incubating these cells with RD114-pseudotyped vector particles. In a specific embodiment, the vector particles are retronectin-immobilized or ultracentrifugation-concentrated retroviral vector particles pseudotyped with the feline endogenous retrovirus (RD114) envelope protein. The present invention further discloses a method for somatic gene therapy, which can be used for various therapeutic applications and involves introducing a gene of interest contained within the retroviral genome into human repopulating stem cells followed by introducing these cells into a human host.Type: GrantFiled: March 7, 2001Date of Patent: February 1, 2005Assignee: St. Jude Children's Research HospitalInventors: Patrick F. Kelly, Elio F. Vanin
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Patent number: 6844156Abstract: The present invention provides a method of identifying a preferred liver transplant donor. The method includes the step of determining in an individual the presence or absence of a preferred genotype at a polymorphic site, where the preferred genotype is associated with altered activity of a tumor necrosis factor, and wherein the presence of the preferred genotype indicates that the individual is a preferred liver transplant donor. A preferred genotype can be associated with lower activity of a tumor necrosis factor such as TNF-? and can be, for example, TNF308.1. The methods of the invention are useful for identifying a preferred donor liver for transplant into a HCV infected patient. The invention additionally provides a method for selecting a preferred liver for transplantation. The invention further provides a method for limiting the recurrence of HCV infection in a liver transplant recipient.Type: GrantFiled: September 12, 2001Date of Patent: January 18, 2005Assignee: The United States of America as represented by the Department of Veterans AffairsInventor: Hugo R. Rosen
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Patent number: 6838592Abstract: The invention features methods for identifying compounds useful for the treatment of Alzheimer's disease.Type: GrantFiled: April 28, 2000Date of Patent: January 4, 2005Assignee: Nathan S. Kline Institute for Psychiatric ResearchInventors: Ralph A. Nixon, Anne M. Cataldo, Paul M. Mathews
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Patent number: 6838444Abstract: Compositions and methods are disclosed for the therapeutic use of an atonal-associated nucleic acid or amino acid sequence. Also, an animal heterozygous for an atonal-associated gene inactivation is also disclosed having at least one atonal-associated nucleic acid sequence replaced by insertion of a heterologous nucleic acid sequence used to detect expression driven by an atonal-associated promoter sequence, wherein the inactivation of the atonal-associated nucleic acid sequence prevents expression of the atonal-associated gene.Type: GrantFiled: June 1, 2000Date of Patent: January 4, 2005Assignee: Baylor College of MedicineInventors: Huda Y. Zoghbi, Hugo J. Bellen, Nessan A. Bermingham, Bassem Hassan, Nissim Ben-Arie