Patents Issued in July 6, 2004
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Patent number: 6759202Abstract: Method and composition for detecting one or more selected polynucleotide regions in a target polynucleotide. In one embodiment of the invention, a plurality of different-sequence probe pairs are added to a target polynucleotide, where each probe pair includes two polynucleotide probe elements which are complementary in sequence to adjacent portions of a selected one of the target sequences in the target polynucleotide. In each probe pair, one of the probe elements contains a non-polynucleotide polymer chain which imparts a distinctive mobility to the associated probe pair, when the elements in the pair are ligated. The other element in the pair contains a detectable reporter label. After the probe pairs have been allowed to hybridize with the target polynucleotide, the hybridized polynucleotides are treated under conditions effective to ligate the end subunits of target-bound probe elements when their end subunits are base-paired with adjacent target bases.Type: GrantFiled: June 10, 2002Date of Patent: July 6, 2004Assignee: Applera CorporationInventors: Paul David Grossman, Steven Fung, Steven Michael Menchen, Sam Lee Woo, Emily Susan Winn-Deen
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Patent number: 6759203Abstract: The present invention provides a method for quantifying the presence of extracellular BPI in body fluids including blood in a subject comprising conducting a BPI immunoassay on body fluid sample obtained from said subject.Type: GrantFiled: October 9, 1998Date of Patent: July 6, 2004Assignee: XOMA CorporationInventors: Mark Leslie White, Stephen Fitzhugh Carroll, Jeremy Kam-kuen Ma
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Patent number: 6759204Abstract: The invention concerns a method for early diagnosis of cancer in a patient which consists in identifying by any appropriate method the presence of autoantibodies directed against the Csk protein in a biological sample taken from said patient. The invention also concerns a kit for implementing said diagnostic method.Type: GrantFiled: December 15, 2000Date of Patent: July 6, 2004Assignee: Centre National de la Recherche Scientifique-CNRSInventors: Christine Benistant, Heliette Chapuis, Nicolas Mottet-Auselo, Serge Roche, Jean-François Bourgaux, Jean-Pierre Bali
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Patent number: 6759205Abstract: A sublancin peptide variant (lantibody) having a spacer region and a subtilin leader peptide fused to the C-terminal end of the mature sublancin peptide provide an anchoring means for inserting and retaining the lantibody in a host cell wall without affecting the intracellular processing of the lantibody, host cell expression of the molecule on the cell surface or the biological activity of the mature sublancin peptide in extracellular, cell-wall-bound form. Target molecules that bind to the lantibody and methods of engineering a peptide variant gene, plasmid and a host cell transformant are described as are methods of using a lantibody to identify new target molecules.Type: GrantFiled: June 29, 2001Date of Patent: July 6, 2004Assignee: University of MarylandInventor: J. Norman Hansen
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Patent number: 6759206Abstract: The present invention provides systems, methods, and screens to measure receptor internalization in a single step with appropriate automation and throughput. This approach involves luminescent labeling of the receptor of interest and the automated measurement of receptor internalization to a perinuclear location.Type: GrantFiled: July 12, 1999Date of Patent: July 6, 2004Assignee: Cellomics, Inc.Inventors: Richard A. Rubin, Kenneth A. Giuliano, Albert H. Gough, R. Terry Dunlay
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Patent number: 6759207Abstract: The present invention relates to novel fluorescent dyes, novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of caspases and other enzymes involved in apoptosis in whole cells, cell lines and tissue samples derived from any living organism or organ. The reporter molecules and assay processes can be used in drug screening procedures to identify compounds which act as inhibitors or inducers of the caspase cascade in whole cells or tissues. The reagents and assays described herein are also useful for determining the chemosensitivity of human cancer cells to treatment with chemotherapeutic drugs. The present invention also relates to novel fluorogenic and fluorescent reporter molecules and new enzyme assay processes that can be used to detect the activity of type 2 methionine aminopeptidase, dipeptidyl peptidase IV, calpain, aminopeptidase, HIV protease, adenovirus protease, HSV-1 protease, HCMV protease and HCV protease.Type: GrantFiled: September 7, 2001Date of Patent: July 6, 2004Assignee: Cytovia, Inc.Inventors: Eckard Weber, Sui Xiong Cai, John F. W. Keana, John A. Drewe, Han-Zhong Zhang
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Patent number: 6759208Abstract: High throughput screening assays for the identification of potential therapeutic agents able to modulate the activity of enzymes of fatty acid biosynthesis, especially desaturases and/or elongases, are disclosed along with therapeutic uses of the agents identified by such assays for the prevention and/or treatment of diseases related to fatty acid metabolism. Substrates useful in such assays are also described.Type: GrantFiled: August 29, 2002Date of Patent: July 6, 2004Assignee: Xenon Genetics Inc.Inventors: Michael D. Winther, Mark P. Gray-Keller
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Patent number: 6759209Abstract: Micro-organisms having a chromosome in which at least one gene has been partly or wholly replaced by a homologous gene from another micro-organism, and an artificially introduced reporter gene is present and is expressed in a manner related to a homologous gene expression product. Panels of such microorganisms are also described. Methods of assessing an agent for antibiotic activity and using the agent as an antibiotic. Methods of killing or inhibiting growth of bacteria.Type: GrantFiled: August 24, 2001Date of Patent: July 6, 2004Assignee: ISIS Innovation LimitedInventor: Jeffrey Errington
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Patent number: 6759210Abstract: The present invention relates to methods and compositions for the treatment and diagnosis of cardiovascular disease, including, but not limited to, atherosclerosis, ischemia/reperfusion, hypertension, restenosis, and arterial inflammation. Specifically, the present invention identifies and describes genes which are differentially expressed in cardiovascular disease states, relative to their expression in normal, or non-cardiovascular disease states, and/or in response to manipulations relevant to cardiovascular disease. Further, the present invention identifies and describes genes via the ability of their gene products to interact with gene products involved in cardiovascular disease. Still further, the present invention provides methods for the identification and therapeutic use of compounds as treatments of cardiovascular disease.Type: GrantFiled: March 28, 1997Date of Patent: July 6, 2004Assignee: Millennium Pharmaceuticals, Inc.Inventors: Dean A. Falb, Michael A. Gimbrone, Jr.
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Patent number: 6759211Abstract: The present invention is generally directed to the identification of mouse and human genes that inhibit the growth of a tumor and induce apoptosis in cancer cells, and to polypeptides encoded by such genes. In particular, the invention concerns the nucleotide sequence of one such tumor-inhibiting gene, tag7, and the amino acid sequence of a polypeptide encoded by tag7. The invention also provides isolated nucleic acid molecules comprising tag7 polynucleotides, and vectors and host cells comprising these isolated nucleic acid molecules. The invention also provides methods of producing tag7 polynucleotides using these nucleic acid molecules, vectors and host cells, tag7 polypeptides made by three methods and antibodies that specifically bind to the tag7 polypeptide. The invention also concerns methods of inhibiting tumor growth and inducing tumor cell apoptosis, and methods of cancer therapy, using the present tag7 nucleic acid molecules and polypeptides.Type: GrantFiled: July 28, 2000Date of Patent: July 6, 2004Assignee: Boehringer Ingelheim International GmbHInventors: Georgii Georgiev, Sergei Kiselev, Egor Prokhorchouk, Elinborg Ostermann
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Patent number: 6759212Abstract: A DNA containing a nucleotide sequence encoding the amino acid sequence shown as SEQ ID NO: 2 in Sequence Listing, or a nucleotide sequence encoding a protein having the amino acid sequence shown as SEQ ID NO: 2 in Sequence Listing with partial substitution, deletion or addition and having cell cycle control activity, or a nucleotide sequence hybridizing to them; a recombinant vector containing said DNA; a cell transformed with said vector; a process for producing AIM-1 using said DNA; a recombinant AIM-1 protein obtained by said process; an oligonucleotide or peptide nucleic acid capable of specifically hybridizing to a nucleotide sequence encoding AIM-1 protein; an antibody recognizing AIM-1; a therapeutic agent for diseases associated with abnormal cell growth containing an inhibitor against AIM-1 protein; and a screening method for materials having serine-threonine inhibitory activity using AIM-1 gene or AIM-1 protein.Type: GrantFiled: February 14, 2000Date of Patent: July 6, 2004Assignee: Chugai Seiyaku Kabushiki KaishaInventors: Masaaki Tatsuka, Yasuhiko Terada
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Patent number: 6759213Abstract: The invention relates to novel Haemophilus adhesion proteins, nucleic acids, and antibodies.Type: GrantFiled: October 4, 2000Date of Patent: July 6, 2004Assignee: Washington UniversityInventors: Joseph St. Geme, Stephen J. Barenkamp
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Patent number: 6759214Abstract: The present invention provides polynucleotides and proteins encoded by such polynucleotides, along with therapeutic, diagnostic and research utilities for these polynucleotides and proteins. In particular, the polypeptides and polynucleotides of the invention comprise amino acid and nucleic acid sequences of novel CD39-like gene and gene products.Type: GrantFiled: July 13, 2001Date of Patent: July 6, 2004Assignee: Nuvelo, Inc.Inventors: Brian Paul Chadwick, Anna-Maria Frischauf
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Patent number: 6759215Abstract: Novel stem cell factors, oligonucleotides encoding the same, and methods of production, are disclosed. Pharmaceutical compositions and methods of treating disorders involving blood cells are also disclosed.Type: GrantFiled: August 7, 2000Date of Patent: July 6, 2004Assignee: Amgen Inc.Inventors: Krisztina M. Zsebo, Robert A. Bosselman, Sidney V. Suggs, Francis H. Martin
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Patent number: 6759216Abstract: The development of inhibitory antibodies to blood coagulation factor VIII (fVIII) results in a severe bleeding tendency. These antibodies arise in patients with hemophilia A (hereditary fVIII deficiency) who have been transfused with fVIII. They also occur in non-hemophiliacs, which produces the condition acquired hemophilia. We describe a method to construct and express novel recombinant fVIII molecules which escape detection by existing inhibitory antibodies (low antigenicity fVIII) and which decrease the likelihood of developing inhibitory antibodies (low immunogenicity fVIII). In this method, fVIII is glycosylated at sites that are known to be antibody recognition sequences (epitopes). This produces the desired properties of low antigenicity fVIII and low (immunogenicity fVIII. The mechanism is similar to one used by viruses such as the AIDS virus, which glycosylates its surface proteins to escape detection by the immune system.Type: GrantFiled: November 5, 1999Date of Patent: July 6, 2004Assignee: Emory UniversityInventor: John S. Lollar
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Patent number: 6759217Abstract: The methods of the invention detect epidermal growth factor RNA, epidermal growth factor receptor RNA, her-2/neu RNA, c-myc RNA, heterogeneous nuclear ribonucleoprotein A2/B1 RNA or any combination thereof in blood plasma, serum, and other bodily fluids. The inventive methods are useful for detection, diagnosis, monitoring, treatment, or evaluation of neoplastic disease.Type: GrantFiled: September 28, 2001Date of Patent: July 6, 2004Assignee: OncoMEDx, Inc.Inventor: Michael S. Kopreski
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Patent number: 6759218Abstract: The present invention provides an isolated polynucleotide containing a polynucleotide sequence selected from the group a) polynucleotide which is at least 70% identical to a polynucleotide which codes for a polypeptide containing the amino acid sequence of SEQ ID no. 2, b) polynucleotide which codes for a polypeptide which contains an amino acid sequence which is at least 70% identical to the amino acid sequence of SEQ ID no. 2, c) polynucleotide which is complementary to the polynucleotides of a) or b), and d) polynucleotide containing at least 15 successive nucleotides of the polynucleotide sequence of a), b) or c), and a process for the fermentative production of L-amino acids with enhancement of the glbO gene which codes for the haemoglobin-like protein and the use of the above polynucleotides as a primer or hybridization probe.Type: GrantFiled: May 7, 2002Date of Patent: July 6, 2004Assignee: Degussa-AGInventors: Bettina Mockel, Achim Marx, Walter Pfefferle
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Patent number: 6759219Abstract: Coexpression of a polyhydroxyalkanoic acid synthase and either a fatty acid: acyl-CoA transferase or an acyl-CoA synthetase in cells enables the biosynthesis of polyester materials. Plasmids, bacteria, materials, and methods for the preparation of polyesters are disclosed.Type: GrantFiled: September 3, 1999Date of Patent: July 6, 2004Assignee: Metabolix, Inc.Inventors: Silke Hein, Brigitte Söhling, Gerhard Gottschalk, Alexander Steinbüchel
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Patent number: 6759220Abstract: A method of increasing loading of active enzyme immobilized in a polyurethane polymer including the steps of: synthesizing the polyurethane polymer in a reaction mixture containing water and enzyme; and including a sufficient amount of a surfactant in the reaction mixture to increase enzyme activity at an enzyme loading.Type: GrantFiled: November 17, 1999Date of Patent: July 6, 2004Assignee: Agentase, LLCInventors: Keith E. LeJeune, Alan J. Russell
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Patent number: 6759221Abstract: A novel human kinase protein and nucleic acid molecule is disclosed. In addition to the isolated kinase protein, the invention further provides isolated kinase fusion proteins, antigenic peptides, and anti-kinase antibodies. The invention also provides kinase nucleic acid molecules, recombinant expression vectors containing a nucleic acid molecule of the invention, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a kinase gene has been introduced or disrupted. Diagnostic, screening, and therapeutic methods utilizing compositions of the invention are also provided.Type: GrantFiled: August 18, 2000Date of Patent: July 6, 2004Assignee: Millennium Pharmaceuticals, Inc.Inventor: Martin R. Hodge
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Patent number: 6759222Abstract: The invention provides isolated nucleic acids molecules, designated 14815 nucleic acid molecules, which encode novel kinase family members. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 14815 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 14815 gene has been introduced or disrupted. The invention still further provides isolated 14815 proteins, fusion proteins, antigenic peptides and anti-14815 antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.Type: GrantFiled: January 2, 2003Date of Patent: July 6, 2004Assignee: Millennium Pharmaceuticals, Inc.Inventor: Rachel E. Meyers
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Patent number: 6759223Abstract: The invention is directed to purified and isolated novel murine and human kinase polypeptides, the nucleic acids encoding such polypeptides, processes for production of recombinant forms of such polypeptides, antibodies generated against these polypeptides, fragmented peptides derived from these polypeptides, and the uses of the above.Type: GrantFiled: January 30, 2003Date of Patent: July 6, 2004Assignee: Immunex CorporationInventors: Timothy A. Bird, G. Duke Virca, Unja Martin, Dirk M. Anderson
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Patent number: 6759224Abstract: An isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of a) polynucleotide which is at least 70% identical to a polynucleotide that codes for a polypeptide which comprises the amino acid sequence of SEQ ID No. 2, b) polynucleotide which codes for a polypeptide that comprises an amino acid sequence which is at least 70% identical to the amino acid sequence of SEQ ID No. 2, c) polynucleotide which is complementary to the polynucleotides of a) or b), and d) polynucleotide comprising at least 15 successive nucleotides of the polynucleotide sequence of a), b) or c), and a process for the fermentative preparation of L-amino acids using coryneform bacteria, in which at least the sahH gene is present in enhanced form, and the use of polynucleotides which contain the sequences according to the invention as hybridization probes.Type: GrantFiled: August 2, 2001Date of Patent: July 6, 2004Assignee: Degussa AGInventors: Mike Farwick, Klaus Huthmacher, Jennifer Brehme, Walter Pfefferle, Michael Binder, Dieter Greissinger, Georg Thierbach
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Patent number: 6759225Abstract: The inventors have isolated lysophospholipases from Aspergillus (A. niger and A. oryzae) having molecular masses of about 68 kDa and amino acid sequences of 600-604 amino acid residues. The novel lysophospholipases have only a limited homology to known amino acid sequences. The inventors also isolated genes encoding the novel enzymes and cloned them into E. coli strains.Type: GrantFiled: December 4, 2002Date of Patent: July 6, 2004Assignee: Novozymes A/SInventors: Hiroaki Udagawa, Torben Peter Frandsen, Tom Anton Busk Nielsen, Markus Sakari Kauppinen, Soren Christensen
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Patent number: 6759226Abstract: The present invention relates to novel enzymes designed for direct detection, characterization and quantitation of nucleic acids, particularly RNA. The present invention provides enzymes that recognize specific nucleic acid cleavage structures formed on a target RNA sequence and that cleave the nucleic acid cleavage structure in a site-specific manner to produce non-target cleavage products. The present invention provides enzymes having an improved ability to specifically cleave a DNA member of a complex comprising DNA and RNA nucleic acid strands.Type: GrantFiled: May 24, 2000Date of Patent: July 6, 2004Assignee: Third Wave Technologies, Inc.Inventors: Wu-Po Ma, Victor I. Lyamichev, Michael W. Kaiser, Natalie E. Lyamicheva, Hatim Taysir Allawi, James J. Schaefer, Bruce P. Neri
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Patent number: 6759227Abstract: Caspases are cysteinyl aspartate-specific proteinases, many of which play a central role in apoptosis. This invention relates to the identification of a new murine caspase and its human homologue. The new molecules are most related to human/murine caspase-2 and human caspase-9 and possesses all the typical amino acid residues of the caspases involved in catalysis, including the QACRG box, and contains no or only a very short prodomain. Northern blot analysis revealed that mRNA expression of the new caspase is predominant in skin.Type: GrantFiled: January 17, 2001Date of Patent: July 6, 2004Assignee: Vlaams Interuniversitair Instituut Voor Biotechnologie VZWInventors: Marc van de Craen, Wim Declercq, Peter Vandenabeele, Walter Fiers
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Patent number: 6759228Abstract: An alkaline protease having the following properties; a gene encoding the same; a microorganism producing the same; and washing compositions containing the same; (i) acting over a broad pH value range of 4 to 13 and achieving, at pH 6 to 12, 80% or more the activity at the optimum pH value; (ii) when treated at 40° C. for 30 minutes, being stable over a pH value range of 6 to 11; (iii) having an isoelectric point of about 8.9 to 9.1; and (iv) having casein digesting activity that is not inhibited by oleic acid. The alkaline protease of the present invention is highly stable to various surface active agents and fatty acids, and exhibits high stability to oxidizing agents, and is therefore useful as an enzyme to be used in detergents for automatic dishwashers and laundry detergents, both containing bleaching components.Type: GrantFiled: August 3, 2001Date of Patent: July 6, 2004Assignee: Kao CorporationInventors: Mikio Takaiwa, Mitsuyoshi Okuda, Katsuhisa Saeki, Hiromi Kubota, Jun Hitomi, Yasushi Kageyama, Shitsuw Shikata, Masafumi Nomura
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Patent number: 6759229Abstract: The invention provides intracellular peptide toxins capable of killing bacterial and eukaryotic cells when present within the cell, while substantially lacking the ability to kill such cells when present externally. The invention also provides recombinant bacteriophage containing nucleic acid sequences encoding intracellular peptide toxins, and methods of using such bacteriophage to kill bacteria. Furthermore, the invention provides compositions, including pharmaceutical compositions, which can be used to kill bacteria or inhibit the growth of bacteria both in vitro and in vivo. Methods of treating a bacterial infection in a subject are also provided by the invention.Type: GrantFiled: December 18, 2001Date of Patent: July 6, 2004Assignee: President & Fellows of Harvard CollegeInventor: Diane L. Schaak
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Patent number: 6759230Abstract: A novel microorganism producing a nontoxic, non-antigenic exopolysaccharide is taught. The exopolysaccharide has neutral sugars migrating at the same rate as mannose, fucose, fructose and galactose, acidic sugars migrating at the same rate as fucose and amine sugars migrating at the same rate as glucose and fucose, and wherein the ratio of galactose:fucose:glucose:mannose is about 1:2:3:6. The microbe and the exopolysaccharide have uses as a biofilm in geologic applications and have several consumer uses as food and drug polymers and use as a plasma extender.Type: GrantFiled: October 25, 2000Date of Patent: July 6, 2004Assignee: The Board of Regents, The University of TexasInventors: Lee A. Bulla, Jr., Mehmet Candas
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Patent number: 6759231Abstract: A &lgr; phage with a nuclear localization signal has been obtained by constructing a vector capable of expressing a fused protein between a gpD protein constituting the head of a &lgr; phage and a nuclear localization signal sequence, transforming Escherichia coli with this vector, and propagating a mutant &lgr; phage which cannot express the gpD protein in E. coli in this transformant. It has been confirmed that the resulting &lgr; phage is capable of packaging &lgr; phage DNAs of 80% and 100% genome sizes. After further confirming that the nuclear localization signal exposed on the outside of the head of this phage, this phage has been microinjected into cells to analyze its nuclear localization activity. Thus, it has been clarified that this phage has a nuclear localization activity.Type: GrantFiled: April 27, 2001Date of Patent: July 6, 2004Assignee: Dnavec Research Inc.Inventors: Mahito Nakanishi, Emi Nagoshi, Teruo Akuta, Katsuo Takeda, Mamoru Hasegawa
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Patent number: 6759232Abstract: Provided is a method for the in vitro aseptic mass production and sporulation of arbuscular mycorrhizal fungi (AMF). The method comprises providing symbiotic root organs with AMF propagules and spores after the root organs are inoculated with AMF inoculums in advance to form AMF propagules in the root organs and cultivating them in an aseptic container, and then providing the whole symbiotic root organs and AMF propagules with liquid medium for a temporary contact between the liquid medium and the root organ with AMF propagules in order to cultivate AMF, then removing the liquid medium from the symbiotic root organs and arbuscular mycorrhizal fungal propagules and finally repeating former two steps periodically to facilitate the mass production and sporulation of the arbuscular mycorrhizal fungi.Type: GrantFiled: April 29, 2002Date of Patent: July 6, 2004Inventor: Wen-Kai Wang
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Patent number: 6759233Abstract: A process for the recovery of plasmids or other DNA from cells using a first filtration step to remove the cellular debris and other large cellular components and then an ultrafiltration step to capture the plasmids or other DNA on the surface of the ultrafiltration membrane where they may be recovered. An apparatus is also taught for enacting the process and comprises an upper microfiltration or coarse filtration membrane and a lower ultrafiltration membrane. The driving force may be the same for both filters or different and may be done sequentially or simultaneously.Type: GrantFiled: March 29, 2001Date of Patent: July 6, 2004Assignee: Millipore CorporationInventor: Jack Thacher Leonard
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Patent number: 6759234Abstract: The present invention provides therapeutic compositions and methods for treating disease conditions in humans associated with an antigen specific immune response by the human to an antigen such as a protein antigen (i.e. allergy and autoimmune diseases). Therapeutic compositions of the invention are reproducible preparations which are suitable for human therapy. Compositions of the invention comprise at least one isolated peptide having a defined sequence of amino acid residues and the composition is capable of down regulating an antigen specific immune response to an offending antigen in a population of humans subject to the antigen specific immune response. Compositions and methods of the invention may be used to treat sensitivity to protein allergens in humans and may also be used to treat autoimmune disease such as rheumatoid arthritis, diabetes, myasthenia gravis, Grave's disease, Good Pasture's syndrome, thyroiditis and multiple sclerosis.Type: GrantFiled: September 2, 1994Date of Patent: July 6, 2004Assignee: Immulogic Pharmaceutical CorporationInventors: Malcolm L. Gefter, Ze′ev Shaked, Malcolm Morville
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Patent number: 6759235Abstract: Improved devices, systems, and methods for sensing and/or identifying signals from within a signal detection region are well-suited for identification of spectral codes. Large numbers of independently identifiable spectral codes can be generated by quite small bodies, and a plurality of such bodies or probes may be present within a detection region. Simultaneously imaging of identifiable spectra from throughout the detection region allows the probes to be identified. As the identifiable spectra can be treated as being generated from a point source within a much larger detection field, a prism, diffractive grading, holographic transmissive grading, or the like can spectrally disperse the images of the labels across a sensor surface. A CCD can identify the relative wavelengths of signals making up the spectra. Absolute signal wavelengths may be identified by determining positions of the labels, by an internal wavelength reference within the spectra, or the like.Type: GrantFiled: April 5, 2001Date of Patent: July 6, 2004Assignee: Quantum Dot CorporationInventors: Stephen A. Empedocles, Andrew R. Watson
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Patent number: 6759236Abstract: The present invention provides a novel approach to gene therapy of restricted areas such as tumors. The methods introduced here comprise: (a) placing a gene of interest in a plasmid vector driven by a heat or light inducible promoter; (b) modifying this vector by including a tetracycline responsive fusion protein which acts as a transcriptional activator, thus permitting regulation of gene expression by varying the levels of drug and; (c) modifying this vector by including DNA sequences that reduce or eliminate expression of genes in normal bystander cells. Also provided are a set of vectors for both sustained and regulable expression. There is also presented novel vectors for the gene therapy treatment of local and metastatic breast, ovarian and prostate cancer.Type: GrantFiled: August 17, 1999Date of Patent: July 6, 2004Assignee: Research Development FoundationInventors: Yuen Kai Fung, Charles Gomer, Anne T'Ang
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Patent number: 6759237Abstract: An improved tet-repressible system is described in which the transgene is expressed under the control of a promoter which is activated upon binding of a fusion protein composed of a reverse tet repressor/activation domain to tet operator sequences located immediately upstream of the transgene promoter. The tet operator sequences are substantially free of interferon inducible response elements (ISRE). The reverse tet repressor is fused to an activation domain which lacks signals for protein clearance, thus extending expression of the fusion protein. Suitably, the tetO sequences are immediately upstream of a quiet promoter.Type: GrantFiled: November 29, 2001Date of Patent: July 6, 2004Assignee: The Trustees of the University of PennsylvaniaInventors: James M. Wilson, Weidong Xiao
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Patent number: 6759238Abstract: The present invention relates to multi-drug resistance, specifically to multi-drug resistant protein 4 (MRP4) and uses thereof. The present invention provides nucleic acid encoding MRP4, MRP4 protein, antibody reactive to MRP4 and discloses MRP4 as perhaps the first mammalian efflux pump described for nucleoside analogs. The present invention provides the first example of a role of MRP4 in drug resistance. Certain patients who develop drug resistance to anti-microbial therapy or anti-cancer therapy may develop cellular resistance mediated by MRP4. Accordingly, the present invention possesses both diagnostic and therapeutic utility as diagnostic kits, including drug assays and screens are contemplated, as well as pharmaceutical compositions and the corresponding methods of their respective use. For example, a diagnostic kit is disclosed that may be used in order to facilitate determination of patient susceptibility to MRP4 mediated drug resistance.Type: GrantFiled: March 31, 1999Date of Patent: July 6, 2004Assignee: St. Jude Children's Research HospitalInventors: John Schuetz, Arnold Fridland
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Patent number: 6759239Abstract: This invention provides a method of generating antigen specific allospecific human suppressor CD8+CD28− T cells. This invention also provides a method of generating xenospecific human suppressor CD8+CD28− T cells. This invention further provides a method of generating allopeptide antigen specific human suppressor CD8+CD28− T cells. Methods of treatment for reduction of risk of rejection of allografts and xenografts and autoimmune diseases using the human suppressor CD8+CD28− T cells so produced are also provides, as are methods of preventing rejection and autoimmune diseases, and vaccines comprising the produced suppressor T cells. Methods of diagnosis to determine whether a level of immuno-suppressant therapy requires a reduction are provided.Type: GrantFiled: December 21, 2000Date of Patent: July 6, 2004Assignee: The Trustees of Columbia University in the City of New YorkInventors: Nicole Suciu-Foca, Raffaello Cortesini, Zhuoru Liu, Chih-Chao Chang
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Patent number: 6759240Abstract: Methods for purifying actin are provided. The methods generally involve the addition of a magnesium salt in a sufficient quantity, whereby G-actin polymerizes to form actin paracrystals, which can be recovered as a purified form of actin.Type: GrantFiled: November 1, 2001Date of Patent: July 6, 2004Assignee: Cytokinetics, Inc.Inventors: James J. Hartman, Fady Malik, Roman Sakowicz, Jeffrey T. Finer
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Patent number: 6759241Abstract: LPS preparations, isolated from gram negative bacterial strains that contain at least one mutation in at least one of the htrB and msbB genes, and methods and therapeutics related thereto. The LPS preparations display both LPS antagonist and adjuvant activities.Type: GrantFiled: February 27, 2003Date of Patent: July 6, 2004Assignee: University of Maryland Biotechnology InstituteInventors: David M. Hone, Richard Crowley, Mohamed Tarek Shata
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Patent number: 6759242Abstract: The present invention relates to the growth of cells in culture under conditions that promote differentiation, cell survival, and/or cellular proliferation. More particularly, culturing neural crest stem cells in low oxygen conditions is described.Type: GrantFiled: October 22, 1999Date of Patent: July 6, 2004Assignee: California Institute of TechnologyInventors: Marie Csete, Sean J. Morrison, Barbara Wold, David J. Anderson
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Patent number: 6759243Abstract: T cell receptors (TCRs) that have higher affinity for a ligand than wild type TCRs are provided. These high affinity TCRs are formed by mutagenizing a T cell receptor protein coding sequence to generate a variegated population of mutants of the T cell receptor protein coding sequence; transforming the T cell receptor mutant coding sequence into yeast cells; inducing expression of the T cell receptor mutant coding sequence on the surface of yeast cells; and selecting those cells expressing T cell receptor mutants that have higher affinity for the peptide/MHC ligand than the wild type T cell receptor protein. The high affinity TCRs can be used in place of an antibody or single chain antibody.Type: GrantFiled: December 6, 2000Date of Patent: July 6, 2004Assignee: Board of Trustees of the University of IllinoisInventors: David M. Kranz, K. Dane Wittrup, Phillip D. Holler
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Patent number: 6759244Abstract: A preparation and a method of making composite blastocysts (CBs) from aggregates of dissociated cells of non-viable pre-embryos are disclosed. The CB is characterized morphologically by having two distinct tissue types, the inner cell mass (ICM) and the trophectoderm (TE), and a blastocoelic cavity (BC). The method of making CBs is an aggregation process (AP) comprising inter alia the following steps: 1) dissociation of discarded pre-embryos; 2) isolation of single nucleated cells from dissociated discarded pre-embryos; 3) microsurgical encapsulation of several cells within a host zona pellucida or artificial aggregation with or without a non-zona vessel; and 5) primary culture of the cell aggregates for multiplication and differentiation of cells. One particularly advantageous embodiment is that the starting material is non-viable pre-embryos. Another advantageous embodiment is that the AP allows individual cells from non-viable pre-embryos to further multiply, and become integrated into CBs.Type: GrantFiled: November 8, 2001Date of Patent: July 6, 2004Assignee: Art Institute of New York and New Jersey, Inc.Inventors: Mina Alikani, Steen Malte Willadsen
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Patent number: 6759245Abstract: The invention features modular cell culturing devices including one or more flat-plate modules, and is based on the discovery that if the flows of liquid medium and oxygenated fluid are separated by a gas-permeable, liquid-impermeable membrane, and the cells are grown attached to the liquid side of the membrane, the device can be used to culture cells with transport of oxygen through the membrane (i.e., direct oxygenation), without regard for the flow rate of the liquid medium passing through the device. The new flow-through cell culturing devices can thus be used to culture cells, e.g., hepatocytes, with high levels of cell function in organ, e.g., liver, assist systems, for production of cells, for production of cell-derived products, such as, proteins or viruses, or for systems to treat biological liquids to remove toxins, such as, ammonia, or add cell-synthesized products, or both.Type: GrantFiled: June 21, 2000Date of Patent: July 6, 2004Assignees: The General Hospital Corporation, Organogenesis Inc.Inventors: Mehmet Toner, Arno W. Tilles, Ulysses J. Balis, Martin L. Yarmush, Maury D. Cosman, Paul A. Dimilla
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Patent number: 6759246Abstract: A control composition, and method of preparing a control composition, that includes stabilized, mammalian granulocytes having altered physical properties so that the granulocytes function as a human lymphocyte analogs when used on an automated blood cell analyzer.Type: GrantFiled: November 30, 2001Date of Patent: July 6, 2004Assignee: Research & Diagnostic Systems, Inc.Inventor: Mark Collins
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Patent number: 6759247Abstract: In analyzing radiation from a sample, single-quanta counting can be used to advantage especially at low levels of radiation energy, e.g. in the detection of fluorescent radiation. Preferred detection techniques include methods in which (i) fluorescence-stimulating radiation is intensity-modulated in accordance with a preselected code, (ii) wherein it is the fluorescent radiation which is intensity-modulated with the preselected code, and (iii) wherein modulation with a preselected code is applied to a sample to influence a property which functionally affects emitted fluorescent radiation. For registration of the signals from a sensing element of a single-photon detector, time of arrival is recorded, optionally in conjunction with registration of time intervals. Advantageously, in the interest of minimizing the number of pulses missed due to close temporal spacing of pulses, D-triggers can be included in counting circuitry.Type: GrantFiled: December 18, 2002Date of Patent: July 6, 2004Assignee: The Research Foundation of State University of New YorkInventors: Serge Luryi, Vera Gorfinkel, Mikhail Gouzman
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Patent number: 6759248Abstract: A semiconductor wafer (10), a method of providing information on a semiconductor wafer (10), a system of semiconductor wafer (10) and reading means, and a method of reading information from a semiconductor wafer (10) are provided. The invention is characterized by magnetic means (14) as information carrier and the respective magnetic sensors (26) to read such information.Type: GrantFiled: September 28, 2001Date of Patent: July 6, 2004Assignee: Motorola, Inc.Inventors: Karl Mautz, Jason Zeakes
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Patent number: 6759249Abstract: A method of fabricating a variable resistance device, wherein the resistance is changed by passing a voltage of various pulse length through the device, includes preparing a silicon substrate; forming a silicon oxide layer on the substrate; depositing a first metal layer on the silicon oxide, wherein the metal of the first metal layer is taken from the group of metals consisting of platinum and iridium; depositing a perovskite metal oxide thin film on the first metal layer; depositing a second metal layer on the perovskite metal oxide, wherein the metal of the second metal layer is taken from the group of metals consisting of platinum and iridium; annealing the structure at a temperature of between about 400° C. to 700° C. for between about five minutes and three hours; and completing the variable resistance device.Type: GrantFiled: February 7, 2002Date of Patent: July 6, 2004Assignee: Sharp Laboratories of America, Inc.Inventors: Wei-Wei Zhuang, Sheng Teng Hsu
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Patent number: 6759250Abstract: The ferroelectric structure including a Pt/Ir layered electrode used in conjunction with a lead germanate (Pb5Ge3O11) thin film is provided. The electrode exhibits good adhesion to the substrate, and barrier properties resistant to oxygen and lead. Ferroelectric properties are improved, without detriment to the leakage current, by using a thin IrO2 layer formed in situ, during the MOCVD lead germanate (Pb5Ge3O11) thin film process. By using a Pt/Ir electrode, a relatively low MOCVD processing temperature is required to achieve c-axis oriented lead germanate (Pb5Ge3O11) thin film. The temperature range of MOCVD c-axis oriented lead germanate (Pb5Ge3O11) thin film on top of Pt/Ir is 400-500° C. Further, a relatively large nucleation density is obtained, as compared to using single-layer iridium electrode. Therefore, the lead germanate (Pb5Ge3O11) thin film has a smooth surface, a homogeneous microstructure, and homogeneous ferroelectric properties.Type: GrantFiled: July 15, 2002Date of Patent: July 6, 2004Assignee: Sharp Laboratories of America, Inc.Inventors: Fengyan Zhang, Tingkai Li, Sheng Teng Hsu
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Patent number: 6759251Abstract: A semiconductor device having ferroelectric memory cells has memory cell transistors each including first and second source/drain regions. Plug electrodes are formed in contact with the first and second source/drain regions, respectively. A ferroelectric capacitor is formed on the plug electrode connected to the first source/drain region. The ferroelectric capacitor includes a first lower electrode formed on the plug electrode, a ferroelectric film formed on the first lower electrode, and an upper electrode formed on the ferroelectric film. A second lower electrode is formed on the plug electrode connected to the second source/drain region. Wiring is formed to connect the upper electrode to the corresponding second lower electrode.Type: GrantFiled: December 17, 2002Date of Patent: July 6, 2004Assignee: Kabushiki Kaisha ToshibaInventor: Tohru Ozaki