The Polynucleotide Is Coated With Or Encapsulated Within A Lipid Containing Material (e.g., Liposome, Etc.) Patents (Class 435/458)
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Publication number: 20030153522Abstract: Disclosed is a method of inhibiting neoplastic cellular proliferation and/or transformation of mammalian cells, including cells of human origin, in vitro or in vivo. The inventive method involves the use of a composition containing a pituitary tumor transforming gene carboxy-terminal peptide (PTTG-C), which can be comprised in a chimeric protein, which has the ability to regulate endogenous pituitary tumor transforming gene (PTTG) expression and/or function in a dominant negative manner. Kits comprising the inventive compositions are also disclosed for the treatment of neoplastic cellular proliferation in vitro or in vivo. Isolated PTTG-C peptides and PTTG-C-containing chimeric proteins are described.Type: ApplicationFiled: September 30, 2002Publication date: August 14, 2003Inventors: Gregory A. Horwitz, Xun Zhang, Shlomo Melmed
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Publication number: 20030153526Abstract: The present invention provides novel compositions and methods for use in the treatment of cancer, specifically, in the treatment of chronic myelogenous leukemia (CML). The compositions contain antisense oligonucleotides that hybridize to Grb2 and Crkl nucleic acids, the gene products of which are known to interact with the tumorigenic protein bcr-abl. Used alone, in conjunction with each other, and even in conjunction with antisense oligonucleotides directed to bcr-abl nucleic acids, these compositions inhibit the proliferation of CML cancer cells.Type: ApplicationFiled: December 20, 2002Publication date: August 14, 2003Inventors: Gabriel Lopez-Berestein, Ana M. Tari, Ralph B. Arlinghaus
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Publication number: 20030153521Abstract: The present invention relates to nucleic acid molecules, including enzymatic nucleic acid molecules, such as DNAzymes (e.g. DNA enzymes, catalytic DNA), that modulate the expression of Ras genes such as K-Ras, H-Ras, and/or N-Ras.Type: ApplicationFiled: September 10, 2002Publication date: August 14, 2003Inventor: James McSwiggen
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Publication number: 20030153083Abstract: Novel methods and compositions for selective killing of cells by activation of PKR are disclosed. In a preferred embodiment, a method is provided for causing cell death in a targeted population of cells that includes the steps of: selecting a nucleotide sequence at a single genetic locus in the targeted population that is absent from the equivalent locus in a population of non-targeted cells; obtaining one or more anti-sense RNA having sequence homology with the locus in the targeted population; permitting the anti-sense RNA to hybridize with an RNA transcribed from the locus in the targeted population so as to form a contiguous double stranded RNA for interacting with PKR. The activation of PKR gives rise to selective cell death in the targeted population.Type: ApplicationFiled: November 15, 2002Publication date: August 14, 2003Inventors: Alexei Shir, Alexander Levitzki
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Patent number: 6602713Abstract: Antisense compounds, compositions and methods are provided for modulating the expression of Protein Phosphatase 2 catalytic subunit beta. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Protein Phosphatase 2 catalytic subunit beta. Methods of using these compounds for modulation of Protein Phosphatase 2 catalytic subunit beta expression and for treatment of diseases associated with expression of Protein Phosphatase 2 catalytic subunit beta are provided.Type: GrantFiled: February 9, 2001Date of Patent: August 5, 2003Assignee: ISIS Pharmaceuticals, Inc.Inventor: Jacqueline Wyatt
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Publication number: 20030144230Abstract: The present invention provides compositions useful for transfecting eukaryotic cells comprising nucleic acid complexes with peptides, wherein the peptide is optionally covalently coupled to a nucleic acid-binding group, and cationic lipids or dendrimers as transfection agents. The invention also provides transfection compositions in which a peptide is covalently linked to the transfection agent (lipid, cationic lipid or dendrimer). Inclusion of peptides or modified-peptides in transfection compositions or covalent attachment of peptides to transfection agents results in enhanced transfection efficiency. Methods for the preparation of transfection compositions and methods of using these transfection compositions as intracellular delivery agents and extracellular targeting agents are also disclosed.Type: ApplicationFiled: July 23, 2002Publication date: July 31, 2003Inventors: Pamela Hawley-Nelson, Jianqing Lan, PoJen Shih, Joel A. Jessee, Kevin P. Schifferli, Gulilat Gebeyehu, Valentina C. Ciccarone, Krista L. Evans
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Publication number: 20030143742Abstract: The present invention provides a composition of matter for introducing an exogenous nucleic acid molecule into a target cell, comprising a liposome, a ligand polymeric scaffold, wherein the ligand can bind to a cell surface receptor or molecule. The invention also provides methods for introducing an exogenous nucleic acid molecule into a target cell using the composition of matter.Type: ApplicationFiled: February 6, 2003Publication date: July 31, 2003Inventor: Randal S. Goomer
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Publication number: 20030143266Abstract: The effective introduction of foreign genes and other biologically active molecules into targeted mammalian cells is a challenge still facing those skilled in the art. Gene therapy, for example, requires successful transfection of target cells in a patient. The present invention relates to novel micellar complexes of cationic amphiphilic compounds that facilitate delivery of biologically active molecules to the targeted cells of a mammal. The novel micellar complexes are comprised of a cationic amphiphile, a biologically active molecule, a derivative of polyethylene glycol (PEG), and optionally, a co-lipid. A further aspect of the invention is the use of targeting agents in any of the methods that effectuate the delivery of biologically active molecules into the cells of mammals. A targeting agent is usually any molecule, peptide sequence, or large protein that preferentially targets or binds to specific mammalian celis.Type: ApplicationFiled: November 22, 2002Publication date: July 31, 2003Applicant: GENZYME CORPORATIONInventors: Jennifer D. Tousignant, Simon J. Eastman, Edward R. Lee, Ronald K. Scheule, Seng H. Cheng, J. Nietupski, Quiming Chu, John Marshall
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Publication number: 20030139344Abstract: The present invention is directed to the pro-apoptotic bok gene product that provides antitumor activity, particularly through induction of apoptosis. In some embodiments of the present invention, Bok is utilized for ovarian cancer, among others, and the composition can be delivered by either viral or non-viral delivery methods.Type: ApplicationFiled: November 19, 2002Publication date: July 24, 2003Inventors: Mien-Chie Hung, Yiyu Zou, Ka Yin Kwong, Geoffrey Bartholomeusz
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Publication number: 20030134423Abstract: Lipids and compositions of lipids that can be used as lipid aggregates (i.e., liposomes) for the delivery of macromolecules and other compounds into cells are provided.Type: ApplicationFiled: January 4, 2002Publication date: July 17, 2003Inventors: Yong Liang Chu, Frank Q. Li, Jian-Tai Qiu, Jerry Lin
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Publication number: 20030133971Abstract: The use of liposomal formulations, particularly formulations of positively charged and neutral lipids facilitates cellular uptake of SDI molecules. The transcription and/or expression of SDI-1-encoding nucleic acid molecules is facilitated by constructs that contain intervening untranslated regions.Type: ApplicationFiled: December 7, 2001Publication date: July 17, 2003Inventors: James R. Smith, Asao Noda, Guy Adami
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Patent number: 6589940Abstract: The invention relates to immunostimulatory oligonucleotide compositions. These oligonucleotides comprise an immunostimulatory octanucleotide sequence. These oligonucleotides can be administered in conjunction with an immunostimulatory peptide or antigen. Methods for modulating an immune response upon administration of the oligonucleotide are also disclosed. In addition, an in vitro screening method to identify oligonucleotides with immunostimulatory activity is provided.Type: GrantFiled: April 22, 1999Date of Patent: July 8, 2003Assignee: Dynavax Technologies CorporationInventors: Eyal Raz, Mark Roman, Dino Dina
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Publication number: 20030124727Abstract: A multivalent cationic lipid having a positively-charged head group including two quaternary amine groups and a hydrophobic portion including four hydrocarbon chains, which may be the same or different and which are optionally substituted alkyl and alkenyl groups, two alkyl chains attached to each of the two quaternary amine groups can be used for the introduction of polyanionic materials such a nucleic acid polymers into cells. Specific cationic lipids are N,N,N′,N′-tetraoleyl-N-N′-dimethyl-1,3-propanediammonium chloride and N,N,N′,N′-tetraoleyl-N-N′-dimethyl-1,6-hexanediammonium chloride.Type: ApplicationFiled: December 18, 2002Publication date: July 3, 2003Inventors: Jerome Gaucheron, Kim Wong, Pieter Cullis
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Publication number: 20030125292Abstract: The present invention relates to compositions and methods for stimulating enhanced mucosal immune responses in vivo. Particularly, the present invention relates to lipid-nucleic acids (“LNA”) formulations and methods of using thereof for stimulating enhanced mucosal immune responses in mammals. More particularly, the present invention relates to improved mucosal vaccines comprising target antigens associated with LNA formulations and methods of using thereof that stimulate antigen-specific mucosal immune responses in mammals.Type: ApplicationFiled: November 7, 2002Publication date: July 3, 2003Inventors: Sean Semple, Sandy Klimuk, Zuan-Ning Yuan
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Publication number: 20030125280Abstract: The invention provides compositions comprising the tissue specific and target RNA-specific ribozyme(s) in either a viral delivery system or a biologic liposome preparation, wherein the viral delivery system or a biologic liposome comprises a pathogen-specific promotor upstream from a sequence encoding a triple ribozyme comprising a) a 5′ autocatalytically cleaving ribozyme sequence, b) a catalytic ribozyme comprising a target RNA-specific binding site and c) a 3′ autocatalytically cleaving ribozyme sequence. The invention also provides methods of treating and/or preventing bacterial infections by administering the compositions of the invention.Type: ApplicationFiled: April 19, 2002Publication date: July 3, 2003Applicants: Medical University of South Carolina, The Penn State Research Foundation, a Pennsylvania corporationInventors: James S. Norris, Michael G. Schmidt, Joseph W. Dolan, Steven D. London, Harold D. May, Gary A. Clawson
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Publication number: 20030118553Abstract: The invention relates to vector constructs, comprising vector DNA which includes regulatory sequences, the NIS gene coding for the sodium/iodide symporter, the TPO gene coding for thyroidal peroxidase and use thereof for production of a medicament/diagnostic for treatment/diagnosis of tumour disease states, whereby treatment occurs before or concurrent with a radionuclide therapy, in particular, with iodine-131, or astatine-211. The invention further relates to use of two or several vector constructs for production of a medicament/diagnostic for treatment/diagnosis of tumour disease states.Type: ApplicationFiled: November 12, 2002Publication date: June 26, 2003Inventors: Thorsten Petrich, Eyck Potter
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Patent number: 6576618Abstract: The present invention describes the incorporation of liposomal gene constructs directly into a wound to further improve wound repair, or into wound coverage and/or closure materials to enhance the functionality of the material. The present invention further describes the use of human fetal membranes (e.g., amnion) enhanced with the liposomal gene therapy as a wound coverage material in full-thickness wound repair. The enhanced fetal membranes or enhanced cadaver skin have advantages over currently used materials lacking the liposomal gene construct and are an efficient and safe approach to improve clinical outcome in patients with burn injuries.Type: GrantFiled: June 22, 2000Date of Patent: June 10, 2003Assignee: Research Development FoundationInventors: David N. Herndon, Jose R. Perez-Polo, Robert E. Barrow
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Publication number: 20030104401Abstract: The present invention provides a stable and efficient method for stimulating RNAi-related gene silencing effects. The present invention also provides a fast, simple and specific method for generating amplified cDNA-aRNA hybrids whose quantity and quality are high enough to be used in specific gene silencing transfection. This improved RNA-polymerase cycling reaction (RNA-PCR) relies upon a thermocycling procedure of in-vitro transcription and reverse transcription to bring up the amount of DNA-RNA hybrids up to two thousand folds within one round of the reaction. The resulting cDNA-aRNA product is useful for silencing either endogenous or exogenous gene expression in transfected cells.Type: ApplicationFiled: January 18, 2002Publication date: June 5, 2003Applicant: Epiclone, Inc.Inventor: Shi-Lung Lin
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Publication number: 20030104044Abstract: Lipid-nucleic acid particles can provide therapeutic benefits, even when the nucleic acid is not complementary to coding sequences in target cells. It has been found that lipid-nucleic acid particles, including those containing non-sequence specific oligodeoxynucleotides, can be used to stimulate cytokine secretion, thus enhancing the overall immune response of a treated mammal. Further, immune response to specific target antigens can be induced by administration of a antigenic molecule in association with lipid particles containing non-sequence specific oligodeoxynucleotides. The nucleic acid which is included in the lipid-nucleic acid particle can be a phosphodiester (i.e.Type: ApplicationFiled: March 1, 2002Publication date: June 5, 2003Inventors: Sean C. Semple, Troy O. Harasym, Sandra K. Klimuk, Ljiljiana D. Kojic, Jonathan L. Bramson, Barbara Mui, Michael J. Hope
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Patent number: 6573101Abstract: The present invention relates generally to the delivery of nucleic acid molecules into cells and, more specifically, to compositions and methods for the high efficiency delivery of nucleic acid molecules into cells.Type: GrantFiled: February 11, 1999Date of Patent: June 3, 2003Assignee: The Regents of the University of CaliforniaInventor: Randal S. Goomer
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Publication number: 20030096786Abstract: A method for stimulating prosaposin receptor activity in a cell by transfecting the cell with a DNA or RNA molecule encoding prosaposin or a prosaposin receptor agonist. The DNA or RNA molecule is administered either in vivo or used to transfect neural cells or neural stem cells ex vivo followed by reintroduction of the cells into an individual.Type: ApplicationFiled: November 13, 2002Publication date: May 22, 2003Inventors: John S. O'Brien, D. Elliot Parks, Susan L. O'Brien
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Patent number: 6566104Abstract: Enzymatic RNA molecules which cleave ErbB-4 mRNA and uses thereof.Type: GrantFiled: June 23, 2000Date of Patent: May 20, 2003Assignee: Georgetown UniversityInventors: Careen K. Tang, Marc E. Lippman
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Publication number: 20030092665Abstract: The present invention provides an economical, nontraumatic and surprisingly effective method for producing a desired protein (especially a biologically active protein) or an antigen using nucleic acid molecules encoding the protein or antigen delivered to a mucosal surface of the animal or human. Expression of the antigen coding sequence exposes the immune system of the animal or human to the antigen with the result that an immune response results, especially an antigen-specific IgA response at mucosal surfaces. Desirably, the nucleic acid molecules are formulated with a bioadhesive agent in an amount sufficient to improve adherence to cells at the mucosal surfaces, thereby improving uptake of the nucleic acid molecules.Type: ApplicationFiled: September 13, 2002Publication date: May 15, 2003Inventor: Richard W. Compans
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Publication number: 20030092655Abstract: &agr;v&bgr;3 Integrin receptor targeting liposomes comprise a cationic amphiphile such as a cationic lipid, a neutral lipid, and a targeting lipid. The targeting lipid includes a non-peptidic &agr;v&bgr;3 integrin antagonist.Type: ApplicationFiled: May 30, 2002Publication date: May 15, 2003Inventors: David A. Cheresh, John Hood, Mark Bednarski
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Publication number: 20030091622Abstract: A method for producing a composition including a nucleic-acid-containing complex is characterized in that two single strand nucleic acid polymers which can at least partly form double strands are separately mixed, in a single strand form, with a cationic carrier or with source materials for the cationic carrier before the cationic carrier is formed. The resulting mixture is then dispersed in water during the production process of the nucleic-acid-containing complex.Type: ApplicationFiled: November 14, 2002Publication date: May 15, 2003Inventors: Katsuhiro Sugihara, Junzo Seki, Kazuko Hirabayashi
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Publication number: 20030087851Abstract: A pharmaceutical composition for treating or preventing influenza comprising an oligonucleotide containing a base sequence complementary to a base sequence of a target region containing a translational initiation codon AUG of a PB2 gene or a PA gene, a liposome stable in blood, and a pharmaceutically acceptable carrier or dilute is disclosed. The pharmaceutical composition for treating or preventing influenza can be used in an effective treatment of or prevention of an infection by influenza viruses.Type: ApplicationFiled: July 19, 2001Publication date: May 8, 2003Applicant: BIOZAK, INC.Inventors: Hiroshi Takaku, Kazuyuki Takai, Toshifumi Hatta, Tadashi Mizuta, Shiro Shigeta, Tomoyuki Yokota
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Patent number: 6559129Abstract: The invention relates to novel cationic lipid formulations and use thereof for treatment of cancer, especially in combination with radiation.Type: GrantFiled: March 30, 2000Date of Patent: May 6, 2003Assignee: Georgetown UniversityInventors: Usha Kasid, Prafulla Gokhale, Chuanbo Zhang, Anatoly Dritschilo, Aquilar Rahman
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Publication number: 20030083249Abstract: Methods of inducing apoptosis in hyperproliferative cells, particularly cancer cells are provided. Such method involves increasing the levels of a potassium channel modulatory protein in the cell. Examples of such proteins are native KChAP protein, a biologically active variant of native KChAP protein, or a biologically active KChAP-related protein (collectively referred to hereinafter as “KChAP protein”). In one embodiment, the cells are contacted with the KChAP protein under conditions permitting uptake of the protein by the cells. In another embodiment, the cells are contacted with (i) a nucleic acid encoding the KChAP protein, and (ii) a promoter active in the cancer cell, wherein the promoter is operably linked to the region encoding the KChAP protein, under conditions permitting the uptake of the nucleic acid by the cancer cell.Type: ApplicationFiled: October 31, 2001Publication date: May 1, 2003Inventors: Arthur M. Brown, Barbara A. Wible
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Publication number: 20030083276Abstract: This invention provides a method for increasing the susceptibility of a cell to DNA-damaging agents, comprising introducing into the cell an antisense oligonucleotide that specifically hybridizes to a nucleic acid encoding a DNA dependent protein kinase subunit so as to prevent expression of the DNA dependent protein kinase subunit; wherein the antisense oligonucleotide is in an amount sufficient to increase the sensitivity of the cell to heat, chemical, or radiation-induced DNA damage; and wherein the DNA dependent protein kinase subunit is a DNA dependent protein kinase catalytic subunit, a Ku70, or a Ku80.Type: ApplicationFiled: December 28, 2000Publication date: May 1, 2003Inventors: Gloria C. Li, Paul W.J.J. Burgman
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Publication number: 20030082154Abstract: Novel lipid compounds are provided that may be termed “pro-cationic” in that they are neutral or negatively charged until they are either brought into contact with cellular membranes or are internalized by cells. The lipids have a hydrophobic tail group and a hydrophilic head group, the head group incorporating both a positively and negatively charged region at physiological pH. The hydrophobic tail group is stably connected to the positive region of the head group which in turn is connected to the negative region by a disulfide bond that is susceptible to cleavage by membrane-bound and intracellular factors. Cleavage of the disulfide bond removes the negatively charged region from the head group resulting in a lipid that is cationic and therefor fusogenic with negatively charged cell membranes. Consequently, lipids of the invention are useful as components of liposomes that serve as vehicles for delivering pharmaceutical agents into cells with reduced toxicity.Type: ApplicationFiled: February 22, 2002Publication date: May 1, 2003Applicant: Isis Pharmaceuticals, Inc.Inventor: Christopher Paul Leamon
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Patent number: 6555673Abstract: Synthetic elements for enhancing expression of genes in plant cells are disclosed. These include a promoter with a “TATA to start” sequence containing 64% or greater GC content and an synthetic upstream element incorporating several OCS binding motifs and novel flanking sequences. Upstream activating regions (UARs) are also disclosed that can further increase the constitutive transcriptional activity when they are operably linked to said promoter and/or the synthetic upstream element. In particular, the nucleotide sequence of the UAR of the maize Ubi-1 gene is provided and its use in expression cassettes and vectors containing these promoter elements. Cells and plants transformed with these vectors are further provided. These include a transgenic sunflower expressing an exogenous oxalate oxidase gene at a high level under the transcriptional control of a recombinant promoter having at least one upstream activating region of the 35S CaMV promoter.Type: GrantFiled: April 21, 2000Date of Patent: April 29, 2003Assignee: Pioneer Hi-Bred International, Inc.Inventors: Benjamin A. Bowen, Wesley B. Bruce, Guihua Lu, Lynne E. Sims, Laura A. Tagliani
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Patent number: 6555376Abstract: The present invention relates to a process of entrapping genetic materials in nanoparticles of inorganic metal salts of size below 100 nm diameter to form non-viral carriers for delivery of genes. The process comprises the steps of dissolving surfactants and a cosurfactant in oil to obtain reverse micelles. An aqueous solution of genetic material is added to the reverse micelles. Thereafter the reverse micelles are divided into two equal parts. To one part, aqueous solution of inorganic metal salts is dissolved to obtain optically clear and transparent reverse micelles. To the second part aqueous solution of precipitating agent is added to obtain optically clear and transparent reverse micelles. The two equally divided parts of reverse micelles are mixed to form inorganic nanopartcles encapsulating added genetic material. Thereafter, the nanoparticles are separated from reverse micelles, the inorganic nanoparticles are dispersed in water and dialyzed to remove free metal salts, surfactant and oil.Type: GrantFiled: July 24, 2002Date of Patent: April 29, 2003Assignee: University of Delhi, Department of ChemistryInventors: Amarnath Maitra, Subho Mozumdar, Susmita Mitra, Indrajit Roy
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Publication number: 20030077829Abstract: The present invention provides lipid-based formulations for delivering nucleic acids to a cell, and assays for optimizing the transfection efficiency of such lipid-based formulations.Type: ApplicationFiled: April 30, 2002Publication date: April 24, 2003Applicant: Protiva Biotherapeutics Inc..Inventor: Ian MacLachlan
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Publication number: 20030077305Abstract: Angiogenic endothelial cells are selectively targeted with lipid/DNA complexes or cationic liposomes containing a substance which affects the targeted cells by inhibiting or promoting their growth. A site of angiogenesis can be precisely located by administering cationic liposomes containing a detectable label. The complexes may comprise nucleotide constructs which are comprised of promoters which are selectively and exclusively activated in the environment of an angiogenic endothelial cell.Type: ApplicationFiled: November 22, 2002Publication date: April 24, 2003Inventors: Donald M. McDonald, John McLean, O. Gavin Thurston, Peter Baluk
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Publication number: 20030078225Abstract: Polyanionic therapeutic compounds, generally nucleic acids, are complexed with calcium phosphate and entrapped within liposomes. For DNA vaccines, the complexation and entrapment process provides improved immune response for gene vaccines delivered intramuscularly.Type: ApplicationFiled: September 26, 2002Publication date: April 24, 2003Inventor: Gregory Gregoriadis
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Publication number: 20030074679Abstract: Growth is improved by utilizing growth enhancement potential methodology to administer a nucleic acid sequence, such as GHRH or an analog, to a female animal, preferably through a parenteral route of administration. Piglets born from sows injected with DNA encoding GHRH are larger, and effects are demonstrated in subsequent pregnancies without additional administration(s) of the vector.Type: ApplicationFiled: December 12, 2001Publication date: April 17, 2003Inventors: Robert J. Schwartz, Ruxandra Draghia-Akli, Roy G. Smith, Douglas R. Kern, Robert H. Carpenter
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Publication number: 20030072794Abstract: A method is disclosed for encapsulating plasmids, oligonucleotides or negatively-charged drugs into liposomes having a different lipid composition between their inner and outer membrane bilayers and able to reach primary tumors and their metastases after intravenous injection to animals and humans. The formulation method includes complex formation between DNA with cationic lipid molecules and fusogenic/NLS peptide conjugates composed of a hydrophobic chain of about 10-20 amino acids and also containing four or more histidine residues or NLS at their one end. The encapsulated molecules display therapeutic efficacy in eradicating a variety of solid human tumors including but not limited to breast carcinoma and prostate carcinoma. Combination of the plasmids, oligonucleotides or negatively-charged drugs with other anti-neoplastic drugs (the positively-charged cis-platin, doxorubicin) encapsulated into liposomes are of therapeutic value.Type: ApplicationFiled: June 8, 2001Publication date: April 17, 2003Inventor: Teni Boulikas
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Publication number: 20030069173Abstract: The present invention provides compositions useful for transfecting eukaryotic cells comprising nucleic acid complexes with peptides, wherein the peptide is optionally covalently coupled to a nucleic acid-binding group, and cationic lipids or dendrimers as transfection agents. The invention also provides transfection compositions in which a peptide is covalently linked to the transfection agent (lipid, cationic lipid or dendrimer). Inclusion of peptides or modified-peptides in transfection compositions or covalent attachment of peptides to transfection agents results in enhanced transfection efficiency. Methods for the preparation of transfection compositions and methods of using these transfection compositions as intracellular delivery agents and extracellular targeting agents are also disclosed.Type: ApplicationFiled: July 23, 2001Publication date: April 10, 2003Applicant: Life Technologies, Inc.Inventors: Pamela Hawley-Nelson, Jianqing Lan, PoJen Shih, Joel A. Jessee, Kevin P. Schifferli, Gulilat Gebeyehu, Valentina C. Ciccarone, Krista L. Evans
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Patent number: 6544955Abstract: The present invention is directed to methods of sensitizing a human tumor cell with adenovirus E1A. The methods involve treating a human tumor cell by, first, introducing into the tumor cell nucleic acid encoding a polypeptide having adenovirus E1A activity, expressing the E1A active polypeptide in the cell, and then either contacting the E1A expressing tumor cell with a chemotherapeutic agent or irradiating the E1A-expressing tumor cell. The invention also provides methods of enhancing a subject's response to chemotherapy or irradiation by introducing into a subject's tumor cells nucleic acid encoding a polypeptide having adenovirus E1A activity, expressing the E1A active polypeptide in the cells and finally, administering either a chemotherapeutic agent or irradiation. The invention also provides a method of treating cancer.Type: GrantFiled: February 23, 2000Date of Patent: April 8, 2003Assignee: The Burnham InstituteInventor: Steven M. Frisch
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Patent number: 6545138Abstract: A method for producing a composition including a nucleic-acid-containing complex is characterized in that two single strand nucleic acid polymers which can at least partly form double strands are separately mixed, in a single strand form, with a cationic carrier or with source materials for the cationic carrier before the cationic carrier is formed. The resulting mixture is then dispersed in water during the production process of the nucleic-acid-containing complex.Type: GrantFiled: November 20, 2000Date of Patent: April 8, 2003Assignee: Nippon Shinyaku Co., Ltd.Inventors: Katsuhiro Sugihara, Junzo Seki, Kazuko Hirabayashi
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Publication number: 20030059897Abstract: The present invention relates to methods of immortalizing various primary cell cultures, including pituitary cells, neurons, beta islet cells, glial cells, corneal epithelial cells and follicular stellate cells. The primary cells are transfected with a vector containing an establishment oncogene, resulting in non-transformed immortalized cells. The primary cells and/or the subsequent immortalized cells are cultured in a defined media containing one or more environmental factor(s) that control the proliferation and/or differentiation of the cells.Type: ApplicationFiled: August 13, 2002Publication date: March 27, 2003Applicant: Vitro Diagnostics, Inc.Inventors: James R. Musick, John Charles Gill, Bruce P. Burnett, Tammy E. Hedlund
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Publication number: 20030054556Abstract: Transfecting compounds which include an aminoglycoside linked to a lipid via a spacer, and their polyguanidylated derivatives are provided. These compounds are useful for the in vitro, ex vivo, or in vivo transfection of nucleic acids into various cell types.Type: ApplicationFiled: August 28, 2002Publication date: March 20, 2003Inventors: Jean-Marie Lehn, Pierre Lehn, Jean-Pierre Vigneron
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Patent number: 6534483Abstract: The present invention, as noted above, relates generally to the incorporation of plasmid into a conventional dosage form, and more particularly to the production of a single-vial, homogenized, plasmid/polymer complex with desirable physical characteristics. Methods of making, storing and using such a complex are also provided and described in detail below. Such products and methods will provide more convenient and cost-effective complexes, which will be protected against chemical degradation and/or physical aggregation of its components and will provide for relative ease of administration. Thus, the present invention provides a more efficient complex for plasmid delivery and a method of incorporation of that plasmid into a conventional dosage form.Type: GrantFiled: August 10, 1999Date of Patent: March 18, 2003Assignee: Valentis, Inc.Inventors: Maria Bruno, Jenna Tagliaferri, Luke Lawson, Mark J. Logan, Russ Mumper
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Publication number: 20030044984Abstract: This invention refers to new surface-active compounds derived from arginine of the mono and diacylglyceride type according to the general formula (I) designed to act as surface agents with antimicrobial activity. The variations in the activity will depend on the number of fatty chains and their length. The purification of the intermediate and final products is achieved by means of liquid/liquid, liquid/solid extractions, crystallizations, ion-exchange chromatography and reverse-phase HPLC.Type: ApplicationFiled: August 7, 2002Publication date: March 6, 2003Inventors: Rosa Infante Martinez, Lourdes Perez Munoz, Carmen Moran Badenas, Pere Clapes Saborit
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Publication number: 20030044983Abstract: The present invention relates to compositions and methods for transferring nucleic acids into cells in vitro and in vivo. The compositions comprise a transfection reagent and one or more detergents. In preferred embodiments, the compositions comprise delivery systems providing nucleic acid transfer complexes that transfect cells with high efficiency.Type: ApplicationFiled: May 31, 2002Publication date: March 6, 2003Inventors: Hans Herweijer, Vladimir G. Budker
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Patent number: 6528312Abstract: Described is the use of a nuclease inhibitor or of interleukin-10 (IL-10) for the preparation of a therapeutic composition for improving transfection of a polynucleotide into a cell, and to compositions comprising a mixture of polynucleotide and nuclease inhibitor and/or interleukin-10.Type: GrantFiled: March 20, 2000Date of Patent: March 4, 2003Assignees: Transgene S.A., Association Francaise Contre les MyopathiesInventor: Serge Braun
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Publication number: 20030039960Abstract: The invention herein described relates to the delivery of therapeutic agents and in particular genetic material, to an animal in combination with dextrin.Type: ApplicationFiled: January 13, 2000Publication date: February 27, 2003Applicant: ML Laboratories PLCInventors: Susan Conroy, Robert Nichol Boyes
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Patent number: 6524815Abstract: The invention relates to the isolation and cloning of the VE-cadherin promoter. It also relates to transformed cells and transgenic animals containing the VE-cadherin promoter. The VE-cadherin promoter of the invention is particularly useful for the tissue-specific expression of a gene of interest in the vascular endothelium.Type: GrantFiled: August 27, 1999Date of Patent: February 25, 2003Assignee: Commissariat a l'Energie Atomique-C.E.A.Inventors: Philippe Huber, Monique Laurent, Sylvie Gory
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Publication number: 20030035829Abstract: The present invention relates to compositions and methods for delivering nucleic acid catalysts e.g., vascular endothelial growth factor receptor (VEGF-R-1) ribozyme, into a biological system.Type: ApplicationFiled: July 23, 1998Publication date: February 20, 2003Applicant: TOWNSEND AND TOWNSEND AND CREWInventors: SEAN C. SEMPLE, SANDRA K. KLIMUK, PETER SCHERRER, MICHAEL J. HOPE, YUAN-PENG ZHANG, MARK REYNOLDS, JOHN MIN
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Patent number: 6521252Abstract: The invention concerns a novel agent for transferring nucleic acids into cells. Said agent is particularly characterised in that it comprises one or several disulphide bonds sensitive to reducing conditions. The invention also concerns compositions comprising such an agent for transferring in vivo, ex vivo or in vitro nucleic acids of interest into different cell types.Type: GrantFiled: July 6, 2000Date of Patent: February 18, 2003Assignee: Aventis Pharma S.A.Inventors: GĂ©rardo Byk, Catherine Dubertret, Bruno Pitard, Daniel Scherman