Patents Issued in January 9, 2001
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Patent number: 6171790Abstract: The invention provides human protease associated proteins (HPRAP) and polynucleotides which identify and encode HPRAP. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating or preventing disorders associated with expression of HPRAP.Type: GrantFiled: May 1, 1998Date of Patent: January 9, 2001Assignee: Incyte Pharmaceuticals, Inc.Inventors: Jennifer L. Hillman, Y. Tom Tang, Preeti Lal, Neil C. Corley, Karl J. Guegler, Chandra Patterson
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Patent number: 6171791Abstract: An isolated and purified nucleic acid comprising a nucleotide sequence which consists of GAT CCA CTG TGC GAC AGC TCG GRG ATC (Seq. Id. No. 1) included in the proto-oncogene RET, which sequence in normal cells has the following sequence in the region defined by position 1810 and adjacent nucleotides including position 1845 and adjacent nucleotides: GAT CCA CTG TGC GAC GAG CTG TGC CGC ACG GTG ATC. Information derived from the altered nucleotide sequence found in a tissue or fluid sample, taken from a patient, can be used for determining the type and character of the rumor. The nucleotide sequence or information derived therefrom is used for the manufacture of reagents for the diagnosing of cancer and for the manufacture of pharmaceutical compositions for prevention and/or treatment of cancer.Type: GrantFiled: November 13, 1998Date of Patent: January 9, 2001Assignee: Karyogene ABInventors: Mansour Alemi, Jan S{umlaut over (a)}llström, Erik Wilander
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Patent number: 6171792Abstract: Disclosed herein are methods for detecting complex protein interactions and protein functional relationships, and reagents for carrying out those methods.Type: GrantFiled: November 10, 1998Date of Patent: January 9, 2001Assignee: The General Hospital CorporationInventors: Roger Brent, C. Wilson Xu, Andrew R. Mendelsohn, Walter L. Lok
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Patent number: 6171793Abstract: A genetic sample is analyzed by providing a gene probe array including a plurality of genetic probes having different receptors. The sample is processed to include at least one fluorescently tagged ligand. The array is hybridized by exposing the probes to the processed sample such that ligands can bind to complementary receptors. Composite data having a data dynamic range is obtained from the array using an optical scanner which has a scanner dynamic range that is smaller than the data dynamic range. The scanner optically irradiates and scans the probes and detects fluorescent emissions at a first wavelength which is selected such that the scanner produces valid first data in a low intensity portion of the data dynamic range and is in saturation in at least part of a high intensity portion of the data dynamic range.Type: GrantFiled: April 19, 1999Date of Patent: January 9, 2001Assignee: Affymetrix, Inc.Inventors: Vincent E. Phillips, Huu Minh Tran, Thomas Ryder, Anthony J. Berno, Ghassan Ghandour
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Patent number: 6171794Abstract: The present invention provides methods for distinguishing the fractions of polynucleotide sequences which hybridize to any given probe, including probes on microarrays such as those described herein. In particular, the present invention enables users to identify the fraction of sequences which are perfectly complementary to a probe, thereby correcting for effects of cross hybridization in a hybridization assay. The methods of the invention work by monitoring the kinetics of dissociation of sequences from the probe so that a resulting “dissociation curve” may be compared to a combination of the individual “dissociation profiles” for each sequence which hybridizes. In alternative embodiments, the invention also provides computer systems for performing the present methods, as well as databases of the dissociation profiles.Type: GrantFiled: June 18, 1999Date of Patent: January 9, 2001Assignee: Rosetta Inpharmatics, Inc.Inventors: Julja Burchard, Roland Stoughton, Stephen H. Friend
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Patent number: 6171795Abstract: Methods are provided for generating nucleic acid ligands of CD40ligand. The methods of the invention use the SELEX method for the isolation of nucleic acid ligands. The invention also includes nucleic acid ligands to CD40ligand, and methods and compositions for the treatment and diagnosis of disease using the nucleic acid ligands.Type: GrantFiled: July 29, 1999Date of Patent: January 9, 2001Assignee: NeXstar Pharmaceuticals, Inc.Inventors: Alan J. Korman, Larry Gold
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Patent number: 6171796Abstract: Disclosed are diagnostic techniques for the detection of human prostate disease. The invention relates particularly to probes and methods for evaluating the presence of RNA species that are differentially expressed in metastatic prostate cancer compared to normal human prostate, benign prostatic hyperplasia, and non-metastatic prostate cancer. The invention also relates to probes and methods for evaluating the presence of RNA species that are differentially expressed in the peripheral blood of individuals with the disease state compared to normal healthy individuals. Described are methods of therapeutic use for genes identified as differentially expressed in metastatic prostate cancer, and means for screening pharmaceuticals effective in treatment of prostate cancer.Type: GrantFiled: August 3, 1999Date of Patent: January 9, 2001Assignee: Urocor, Inc.Inventors: Gang An, Robert W. Vertri
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Patent number: 6171797Abstract: Methods are provided for making arrays of distinct polymers covalently bonded to the surface of the a solid support. In the subject methods, at least two distinct polymers, e.g. nucleic acids, are contacted with the surface of a solid support under conditions sufficient for the nucleic acids to become covalently bonded to the surface of the solid support through a cycloaddition reaction, e.g. through the reaction of a diene with a dienophile. Also provided are arrays produced by the subject methods, kits comprising the same and methods for using the arrays in analyte detection, e.g. hybridization, assays.Type: GrantFiled: October 20, 1999Date of Patent: January 9, 2001Assignee: Agilent Technologies Inc.Inventor: Michel G. M. Perbost
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Patent number: 6171798Abstract: Many genes are identified as being p53-regulated which were not heretofore known to be p53-regulated. This includes both genes whose expression is induced and genes whose expression is repressed by the expression of wild-type p53. Monitoring expression of these genes is used to provide indications of p53 status in a cell. Such monitoring can also be used to screen for useful anti-cancer therapeutics, as well as for substances which are carcinogenic. Defects in p53 can be bypassed by supplying p53 induced genes to cells. Defects in p53 can also be bypassed by supplying antisense constructs to p53-repressed genes.Type: GrantFiled: November 17, 1999Date of Patent: January 9, 2001Assignees: Affymetrix, Inc., Princeton UniversityInventors: Arnold L. Levine, Maureen Elizabeth Murphy, David H. Mack, Kurt Carlyle Gish, Edward Yat Wah Tom
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Patent number: 6171799Abstract: The present invention relates to monoclonal antibodies which recognize defined regions of the T-cell receptor (TCR). In a specific embodiment, the invention provides monoclonal antibodies which are reactive with a constant region of the alpha chain of the TCR. In particular embodiments, the invention relates to two monoclonal antibodies, termed &agr;F1 and &agr;F2, which react with two different epitopes on the framework region of the &agr; monomer of the TCR molecule. In another specific embodiment, the invention is directed to monoclonal antibodies reactive with a variable region of the beta chain of the TCR. In particular, the invention provides two monoclonal antibodies, termed W112 and 2D1, which react with &bgr; chain variable regions V&bgr;5.3 and V&bgr;8.1, respectively. In another specific embodiment, the invention is directed to monoclonal antibodies reactive with a variable region of the delta chain of the TCR. In particular, the invention provides monoclonal antibody &dgr;TCS1, isotype IgG2a.Type: GrantFiled: May 25, 1995Date of Patent: January 9, 2001Assignee: Astra ABInventors: Robert V. Skibbens, Larry D. Henry, Charles W. Rittershaus, Wei-Tao Tian, Stephen H. Ip, Patrick C. Kung, Mary Ellen Snider, Jone-Long Ko, Nancy L. Wood
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Patent number: 6171800Abstract: CAIP polypeptide, nucleic acids, ands uses thereof. A method of evaluating a compound for the ability to bind a CAIP polypeptide; fragment or analog thereof is described.Type: GrantFiled: June 7, 1995Date of Patent: January 9, 2001Assignee: Biogen, Inc.Inventor: Yen-Ming Hsu
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Patent number: 6171801Abstract: One aspect of the present invention relates to a method for releasing a ligand from a complex thereof. The method comprises contacting a medium suspected of containing such complex with an effective amount of a compound effective in releasing the ligand. Another aspect of the present invention is an improvement in a method for the determination of an analyte that is a member of a specific binding pair in a sample suspected of containing such analyte. The method comprises the steps of (a) providing in an assay medium the sample and a binding partner for the analyte and (b) detecting the binding of the binding partner to the analyte. The improvement comprises including in the assay medium a compound of the invention in an amount sufficient to enhance the accuracy of the determination. The invention has particular application to a method for releasing mycophenolic acid from a complex thereof.Type: GrantFiled: July 17, 1997Date of Patent: January 9, 2001Assignee: Dade Behring Marburg GmbHInventors: Mark A. Staples, Carolyn J. Haley, Richard F. Parrish, Wesley W. Zmolek
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Patent number: 6171802Abstract: A system for the detection of ligands comprising at least one receptor and an amplification mechanism coupled to the receptor wherein an amplified signal is produced as a result of receptor binding a ligand. Examples of suitable amplification mechanisms include antibody-embedded liquid crystalline materials; use of alpha-2-macroglobulin to encage an enzyme, whereby the enzyme is separated from its substrate by an receptor; and a receptor engineered to inhibit the active of site of an enzyme only in the absence of a ligand. Also provided are methods for the automatic detection of ligands.Type: GrantFiled: June 10, 1998Date of Patent: January 9, 2001Assignee: Kent State UniversityInventors: Christopher J. Woolverton, Gary D. Niehaus, Kathleen J. Doane, Oleg Lavrentovich, Steven P. Schmidt, Steven A. Signs
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Patent number: 6171803Abstract: The present invention relates to nucleic acid sequences, encoding amino acid sequences of the &agr;, &bgr;, and &ggr; subunits of the high affinity receptor for immunoglobulin E, and for amino acid sequences of the subunits. The invention further relates to a method of producing the receptor by expressing cDNA for its &agr;, &bgr;, and &ggr; subunits in a host cell simultaneously. Aspects of the invention are methods and compositions to inhibit the function of the human beta subunit, thereby treating or preventing allergic reactions.Type: GrantFiled: June 23, 1998Date of Patent: January 9, 2001Assignee: The United States Government as represented by the Department of Health and Human ServicesInventor: Jean Pierre Kinet
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Patent number: 6171804Abstract: The present invention provides methods for determining the relative orientation of the individual components of a macromolecule in solution with respect to the global molecular coordinate frame of the macromolecule. The present invention further provides methods for applying this structural information, including for rational drug design.Type: GrantFiled: July 12, 1999Date of Patent: January 9, 2001Assignee: The Rockefeller UniversityInventors: David Cowburn, Rong Xu, David Fushman
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Patent number: 6171805Abstract: A DNA encoding a cell surface polypeptide of Porphyromonas gingivalis, and a recombinant DNA being a DNA having integrated said DNA thereinto. The cell surface polypeptide of the periodontopathic organism useful for prophylaxis and diagnosis of periodontal diseases can be obtained in a large amount by a microorganism containing the recombinant DNA wherein the DNA was integrated.Type: GrantFiled: May 27, 1999Date of Patent: January 9, 2001Assignees: Kyowa Hakko Kogyo Co., Ltd., Kyowa Medex Co., Ltd,, Meito Sangyo Kabushiki KaishaInventors: Hideharu Mori, Mamoru Hasegawa, Masanori Fukui, Kenji Yasuda, Keiko Yamada, Shusaburo Hokukoku, Tomohiko Ogawa
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Patent number: 6171806Abstract: Tumor rejection antigens presented by HLA-B44 molecules are described. These peptides are useful in diagnostic and therapeutic methodologies. The tumor rejection antigens are not derived from tyrosinase, which has previously been identified as a tumor rejection antigen precursor processed to an antigen presented by HLA-B44.Type: GrantFiled: March 11, 1999Date of Patent: January 9, 2001Assignee: Ludwig Institute for Cancer ResearchInventors: Jean Herman, Pierre Coulie, Pierre van der Bruggen, Thierry Boon-Falleur
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Patent number: 6171807Abstract: Fluorescently labeled ENP as well as methods of preparation are disclosed. Also disclosed is a method of detecting endotoxin in a liquid sample suspected of containing endotoxin, comprising admixing said liquid sample with fluorescently labeled ENP for a time sufficient to form a complex between the labeled ENP and the endotoxin, and performing fluorescence polarization experiment on the sample, wherein a change in the fluorescence polarization indicates the presence of endotoxin.Type: GrantFiled: November 10, 1997Date of Patent: January 9, 2001Assignee: Associates of Cape Cod, Inc.Inventors: Thomas J. Novitsky, Richard J. Ridge, Jack L. Sloyer
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Patent number: 6171808Abstract: Proteins are provided having luciferase activity with lower Km than wild-type luciferases by altering the amino acid residue at position 270 of the wild-type to an amino acid other than glutamate. Greater heat stability than wild-type luciferases while retaining the lower Km is provided by also replacing the glutamate equivalent to that at position 354 of Photinus pyralis luciferase or 356 of Luciola luciferases with an alternative amino acid, particularly lysine and/or the amino acid residue at 215 of Photinus pyralis and 217 of the Luciola species with a hydrophobic amino acid. DNA, vectors and cells that encode for and express the proteins are also provided as are test kits and reagents for carrying out luminescence assays using the proteins of the invention.Type: GrantFiled: October 1, 1997Date of Patent: January 9, 2001Assignee: The Secretary of State for Defence in Her Britannic Majesty's Government of the United Kingdom of Great Britain and Northern IrelandInventors: David J Squirrell, Christopher R Lowe, Peter J White, James A H Murray
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Patent number: 6171809Abstract: The presence of renilla luciferase alone or both renilla luciferase and firefly luciferase is detected by adding reagent mixture(s) to a biological sample and producing glow luminescence having a duration of at least an hour. In producing luminescence from renilla luciferase alone, a reagent is added comprising coelenterazine, and dithiothreitol (DTT) and EDTA, or functional equivalents of DTT and EDTA. Luminescence from samples containing both firefly luciferase and renilla luciferase is produced by first adding a reagent comprising firefly luciferin, ATP, co-factors necessary for firefly luciferase activity (e.g., Ca+2 and Mg+2), dithiothreitol (DTT) or functional equivalents thereof, and AMP. Following measurement of the firefly luciferase, coelenterazine and EDTA, or functional equivalents of EDTA, are added, and the luminescence produced by renilla luciferase is measured.Type: GrantFiled: January 29, 1998Date of Patent: January 9, 2001Assignee: Packard Instrument CompanyInventor: Christiaan Roelant
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Patent number: 6171810Abstract: A method for detecting and measuring exoglycosidase activity is presented. The method employs derivatives containing the fluorescent group 4-methylumbelliferyl (“4-Mu”) at a pH lower than that conventionally employed. While the fluorescence intensity due to the 4-Mu group is considerably diminished at the lower pHs employed, the fluorescence intensity is still sufficient to continuously measure exoglycosidase activity in the activity range commonly assayed. The method is easily adaptable to high throughput enzyme assay systems and automated data analysis method. The method also provides a means to detect alterations in exoglycosidase activity that are independent of expression levels.Type: GrantFiled: April 7, 1999Date of Patent: January 9, 2001Assignee: New York Blood Center, Inc.Inventor: Alex Zhu
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Patent number: 6171811Abstract: The method is based on the carbon-13 labelled urea breath test, which comprises a) administering to the patient an aqueous solution of citric acid at pH comprised between 2 and 2.5; b) collecting a sample of the patient's breath with the object of determining the baseline content of carbon-13; c) administering to the patient a suitable amount of carbon-13 labelled urea; d) collecting a sample of the patient's breath with the object of determining the content of carbon-13 after the administration of the labelled urea; and e) analyzing the breath samples collected to determine the carbon-13 content before and after the administration of urea labelled with carbon-13. The kit has a container for the citric acid, another for the carbon-13 labelled urea, exetainers destined to containing the patient's breath, and means to blow the breath into the exetainers.Type: GrantFiled: July 20, 1999Date of Patent: January 9, 2001Assignee: Isomed, S.L.Inventor: Ana Becerro De Bengoa Vallejo
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Patent number: 6171812Abstract: The system provides frame means, mechanical loading means, electronic control means and perfusion chamber means in which an accurately cut human or animal trabecular bone sample can be maintained in a viable state for an extended period. A chamber is provided which permits perfusion of the trabecular bone sample with suitable media. Mechanical means are provided for loading of the sample under controlled specified conditions. Second messenger and growth factors may be collected from the perfusion chamber effluent to enable study of samples under a wide variety of perfusion and loading conditions. The system allows viability of the sample to be maintained for in excess of 14 days and permits the study of rate of bone formation and the rate of resorption of trabecular bone.Type: GrantFiled: July 6, 1998Date of Patent: January 9, 2001Assignee: The National Institute of Biogerontology, Inc.Inventors: Evertt L. Smith, David Jones
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Patent number: 6171813Abstract: A method is presented for catalyzing the conversion of substrate into product in an organic reaction solvent with an enzyme-surfactant ion pair. The enzyme-surfactant ion pair comprises the enzyme catalyzing the reaction and a surfactant capable of forming an ion pair with the enzyme. Water present in the organic solvent at a concentration of about 0.03% to about 2.5% is sufficient to enhance the rate of catalysis and stabilize the enzyme without substantially increasing the rate of hydrolysis when compared to the anhydrous enzyme.Type: GrantFiled: October 16, 1997Date of Patent: January 9, 2001Assignees: BioTechnology Research & Develop. Corp., The University of Iowa Research FoundationInventors: Jonathan S. Dordick, Vikram M. Paradkar, Maria V. Sergeeva
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Patent number: 6171814Abstract: A process for increasing the amount of clavam produced by an organism having both a clavam pathway or a portion thereof and a cephalosporin pathway or a portion thereof by interfering with the conversion of L-lysine to L-&agr;-aminoadipic acid in the cephalosporin pathway. Plasmids containing a defective LAT (lysine amino transferase) gene and organisms containing such plasmids are also provided.Type: GrantFiled: May 11, 1998Date of Patent: January 9, 2001Assignees: SmithKline Beecham p.l.c., The Governors of the University of AlbertaInventors: William Henry Holms, Ashish Sudhakar Paradkar, Roy Henry Mosher
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Patent number: 6171815Abstract: The present invention provides a human sulfonylurea receptor (SURH) and the polynucleotides which identify and encode SURH. The invention also provides genetically engineered expression vectors and host cells comprising the nucleic acid sequences encoding SURH and methods for producing the protein. The invention also provides pharmaceutical compositions containing SURH, agonists to SURH, or antagonists to SURH, and in the use of such compositions for the prevention or treatment of diseases associated with the expression of SURH. Additionally, the invention provides for the use of antisense molecules to polynucleotides encoding SURH for the treatment of diseases associated with the expression of SURH. The invention also provides diagnostic assays which utilize the polynucleotide, or fragments or the complement thereof, to hybridize to the genomic sequence or transcripts of polynucleotides encoding SURH, or anti-SURH antibodies which specifically bind to SURH.Type: GrantFiled: October 2, 1996Date of Patent: January 9, 2001Assignee: Incyte Pharmaceuticals, Inc.Inventors: Janice Au-Young, Olga Bandman, Roger Coleman
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Patent number: 6171816Abstract: The present invention relates to huXAG-1, huXAG-2 and huXAG-3 proteins which are novel human growth factors. In particular, isolated nucleic acid molecules are provided encoding the huXAG-1, huXAG-2 and huXAG-3 proteins. huXAG-1, huXAG-2 and huXAG-3 polypeptides are also provided as are vectors, host cells and recombinant methods for producing the same. The invention further relates to screening methods for identifying agonists and antagonists of huXAG-1, huXAG-2 or huXAG-3 activity. Also provided are diagnostic and therapeutic uses of huXAG-1. huXAG-2 and huXAG-3.Type: GrantFiled: August 22, 1997Date of Patent: January 9, 2001Assignee: Human Genome Sciences, Inc.Inventors: Guo-Liang Yu, Patrick J. Dillon, Reinhard Ebner, Gregory A. Endress
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Patent number: 6171817Abstract: Novel vectors are disclosed for expressing and secreting heterologous polypeptides from filamentous fungi. Such vectors are used in novel processes to express and secrete such heterologous polypeptides. The vectors used for transforming a filamentous fungus to express and secrete a heterologous polypeptide include a DNA sequence encoding a heterologous polypeptide and a DNA sequence encoding a signal sequence which is functional in a secretory system in a given filamentous fungus and which is operably linked to the sequence encoding the heterologous polypeptide. Such signal sequences may be the signal sequence normally associated with the heterologous polypeptides or may be derived from other sources. The vector may also contain DNA sequences encoding a promoter sequence which is functionally recognized by the filamentous fungus and which is operably linked to the DNA sequence encoding the signal sequence.Type: GrantFiled: November 24, 1997Date of Patent: January 9, 2001Assignee: Genencor International, Inc.Inventors: Randy Michael Berka, Daniel Cullen, Gregory Lawrence Gray, Kirk James Hayenga, Virgil Bryan Lawlis
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Patent number: 6171818Abstract: The present invention relates to a protein having an anti-tumoral effect, a DNA encoding such a protein, and a process for the preparation of such a protein as well as its use.Type: GrantFiled: September 22, 1998Date of Patent: January 9, 2001Assignee: Bioxen LtdInventor: Christian Petzelt
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Patent number: 6171819Abstract: The invention relates to a method of performing a chemical reaction between a reagent and a substrate, involving an acyl transfer mechanism, in the presence of an imidazole-based catalyst capable of forming a transition complex with the substrate. The catalytic imidazole function is provided by a chemical structure element comprising an optionally substituted imidazolyl group flanked on one or both sides by a group or groups capable of stabilizing the transition complex by molecular interaction with the acyl group. The invention also relates to such a designed chemical structure element, a method of producing it by recombinant DNA techniques and a vector therefor.Type: GrantFiled: December 2, 1998Date of Patent: January 9, 2001Assignee: A + Science Invest ABInventors: Per Ahlberg, Lars Baltzer
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Patent number: 6171820Abstract: Disclosed is a rapid and facilitated method of producing from a parental template polynucleotide, a set of mutagenized progeny polynucleotides whereby at each original codon position there is produced at least one substitute codon encoding each of the 20 naturally encoded amino acids. Accordingly, there is also provided a method of producing from a parental template polypeptide, a set of mutagenized progeny polypeptides wherein each of the 20 naturally encoded amino acids is represented at each original amino acid position. The method provided is termed site-saturation mutagenesis, or simply saturation mutagenesis, and can be used in combination with other mutagenization processes, such as, for example, a process wherein two or more related polynucleotides are introduced into a suitable host cell such that a hybrid polynucleotide is generated by recombination and reductive reassortment.Type: GrantFiled: February 4, 1999Date of Patent: January 9, 2001Assignee: Diversa CorporationInventor: Jay M. Short
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Patent number: 6171821Abstract: The invention features purified nucleic acid encoding a novel internal ribosome entry site (IRES) sequence from the X-linked inhibitor of apoptosis (XIAP) gene. The invention also features methods for using the XIAP IRES to increase cap-independent translation of polypeptide coding sequences linked to the XIAP IRES, and methods for isolating compounds that modulate cap-independent translation.Type: GrantFiled: June 14, 1999Date of Patent: January 9, 2001Assignee: Apoptogen, Inc.Inventors: Robert G. Korneluk, Martin Holcik, Peter Liston
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Patent number: 6171822Abstract: The present invention relates to polynucleotide and polypeptide molecules for stanniocalcin-2, a novel member of the stanniocalcin family. The polypeptides, and polynucleotides encoding them, modulate electrolyte homeostasis. The present invention also includes antibodies to the stanniocalcin-2 polypeptides.Type: GrantFiled: October 11, 1999Date of Patent: January 9, 2001Assignee: ZymoGenetics, Inc.Inventors: Rolf E. Kuestner, Darrell C. Conklin, Si Lok, Michele Buddle, William Downey
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Patent number: 6171823Abstract: The invention relates to a method of producing an extracellular protein in a bacterium provided with an inner and an outer cell membrane, the method comprising: (a) providing a recombinant vector including a DNA construct comprising a DNA sequence encoding the prepropeptide or part of the prepropeptide of a bacterial extracellular protease selected from the group consisting of Achromobacter lyticus protease I, Bacillus metalloproteases and Bacillus serine proteases preceding and operably connected to a DNA sequence encoding a desired protein, (b) transforming cells of a microorganism provided with an inner and outer cell membrane with the recombinant vector of step (a), (c) culturing the transformed cells of step (b) under conditions permitting expression of said DNA insert and leakage of the bacterial extracellular protease propeptide fused to the desired protein into the culture medium, and (d) recovering the resulting protein from the medium.Type: GrantFiled: June 2, 1997Date of Patent: January 9, 2001Assignee: Novo Nordisk A/SInventors: Helle Fabricius Wöldike, Sven Hastrup
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Patent number: 6171824Abstract: Therapeutic hybrid cytokines, having a size ranging from about 10 to about 30 kDa, comprise portions of cytokines: leukemia inhibitory factor (LIF), granulocyte-colony stimulating factor (G-CSF), interleukin-6 (IL-6), interleukin-11 (IL-11), oncostatin-M (OSM), and ciliaryneurotrophic factor (CNTF). Hybrid cytokines comprise three or four &agr;-helical sequences selected from &agr;-helical sequences of IL-6, G-CSF, LIF, IL-11, CNTF and OSM and linking sequences of 5-40 amino acids in length, selected from the linking sequences of IL-6, G-CSF, LIF, IL-11, CNTF and OSM or other, desirable linking sequences. In the hybrid cytokines, at least one &agr;-helical sequence is derived from a different cytokine than at least one other &agr;-helical sequence; or, at least one linking sequence of a cytokine differentiates the hybrid cytokine from a corresponding cytokine.Type: GrantFiled: November 8, 1993Date of Patent: January 9, 2001Assignee: Fred Hutchinson Cancer Research CenterInventors: George J. Todaro, David W. Leung, Timothy M. Rose
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Patent number: 6171825Abstract: Recombinant Factor VIII can be produced in relatively large quantities on a continuous basis from mammalian cells in the absence of any animal-derived proteins such as albumin by culturing the cells in a protein free medium supplemented with polyol copolymers, preferably in the presence of trace metals such as copper. In very preferred embodiments, the medium includes a polyglycol known as Pluronic F-68, copper sulfate, ferrous sulfate/EDTA complex, and salts of trace metals such as manganese, molybdenum, silicon, lithium and chromium. With an alternative medium which included trace copper ions alone (without polyol copolymers) we were also able to enhance the productivity of Factor VIII in recombinant cells such as BHK cells that are genetically engineered to express Factor VIII.Type: GrantFiled: September 4, 1998Date of Patent: January 9, 2001Assignee: Bayer CorporationInventors: Sham-Yuen Chan, Kathleen Harris
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Patent number: 6171826Abstract: The present invention relates to methods of controlling beta dimer formation in hemoglobin solutions by altering the metal binding site adjacent to the N-terminus of beta globins. The invention further relates to methods of producing stable, intramolecularly crosslinked beta globins by exposure to Ni(II) and oxone.Type: GrantFiled: May 14, 1999Date of Patent: January 9, 2001Assignee: Baxter Biotech Technology SarlInventors: Joseph D. Levine, Izydor A. Apostol
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Patent number: 6171827Abstract: There is disclosed molecules comprising at least a first moiety having the activity of a procollagen C-propeptide and a second moiety selected from any one of the group of an alien collagen &agr;-chain and non-collagen materials, the first moiety being attached to the second moiety. Also disclosed are collagen molecules, fibrils and fibres comprising a non-natural combination of collagen &agr;-chains, DNA encoding same, expression hosts transformed or transfected with same, transgenic animals and methods of producing a non-natural collagen.Type: GrantFiled: May 7, 1998Date of Patent: January 9, 2001Assignee: The Victoria University of ManchesterInventors: Neil Bulleid, Karl Kadler
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Patent number: 6171828Abstract: The present invention discloses a method for culturing microorganisms having a methanol metabolic pathway in which an expression unit is introduced that comprises a target gene linked downstream from a promoter that can be induced by methanol; wherein, during the culturing period, and including the period during which methanol is continuously or periodically added, the rate of addition is adjusted to a rate equal to or less than the maximum methanol consumption rate of said microorganisms.Type: GrantFiled: March 4, 1997Date of Patent: January 9, 2001Assignee: Suntory LimitedInventors: Koji Magota, Tomohiro Rogi, Yasuyoshi Sakai, Nobuo Kato
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Patent number: 6171829Abstract: A substance PF1191 having an inhibitory activity to kainic acid toxicity represented by the following formula (I) which is obtained by incubating a fungus belonging to the genus Eupenicillium and isolating the product thus produced from the culture by solvent extraction, adsorption column chromatography, gel filtration, etc.Type: GrantFiled: September 10, 1999Date of Patent: January 9, 2001Assignee: Meiji Seika Kaisha, Ltd.Inventors: Haruo Seto, Kazuo Shin-Ya, Takashi Yaguchi, Toru Sasaki
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Patent number: 6171830Abstract: A method of purifying mycolic acids, salts thereof or derivatives thereof. The method involves a) providing a mixture including the mycolic acids, salts thereof or derivatives thereof and contaminants; b) dissolving the mixture in a bi-phasic solvent to form a dissolved mixture including the mycolic acids, salts thereof or derivatives thereof and contaminants; c) purifying the mycolic acids, salts thereof or derivatives thereof by subjecting the dissolved mixture to countercurrent distribution separation involving a sufficient number of cycles to separate the mycolic acids, salts thereof or derivatives thereof from the contaminants; and d) removing the separated, purified mycolic acids, salts thereof or derivatives thereof from the bi-phasic solvent. Residual impurities may be extracted from the removed mycolic acids, salts thereof or derivatives thereof with acetone.Type: GrantFiled: November 6, 1997Date of Patent: January 9, 2001Assignee: Adcock Ingram LimitedInventor: Jan Adrianus Verschoor
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Patent number: 6171831Abstract: The method to produce itaconic acid is a solid-state fermentation method. Sugarcane pressmud or peeled sugarcane pressmud is the support used to adsorb liquid medium for the production of itaconic acid by an Aspergillus terreus mutant strain. This mutant strain was derived from Aspergillus terreus ATCC 10020 by successive mutation. Beside the remaining sucrose in the sugarcane pressmud, other carbon source can be added, i.e. glucose, fructose, sucrose, or starch hydrolysate. Appropriate amounts of nitrogen source, such as ammonium nitrate, or ammonium sulfate are added. Mineral salts, such as potassium dihydrogen phosphate, magnesium sulfate, calcium sulfate, ferric chloride, zinc sulfate, and copper sulfate can be added to the medium. The suitable amount of liquid medium that can be added to the support is 4 to 6 times its dry weight for the sugarcane pressmud and 8 to 14 times its dry weight for the peeled sugarcane pressmud. The optimal pH of the medium is between 2.0-3.0.Type: GrantFiled: February 22, 2000Date of Patent: January 9, 2001Assignee: National Science CouncilInventors: Ying-Chieh Tsai, Min-Chang Huang, Shuen-Fuh Lin, Yuan-Chi Su
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Patent number: 6171832Abstract: A process for preparing cis-(1S,2R)-indanediol is disclosed. The process comprises (A) fermenting a culture medium containing a yeast strain selected from the group consisting of Trichosporon cutaneum MY 1506 (ATCC 74440) and mutants thereof and 1,2-indanedione to form cis-(1S,2R)-indanediol; and (B) recovering cis-(1S,2R)-indanediol from the culture medium. A process for preparing (1S)-amino-(2R)-indanol from the recovered cis-(1S,2R)-indanediol via the Ritter reaction is also disclosed.Type: GrantFiled: April 27, 1999Date of Patent: January 9, 2001Assignee: Merck & Co., Inc.Inventors: Michael M. Chartrain, Norihiro Ikemoto, Anthony O. King
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Patent number: 6171833Abstract: The present invention concerns an anaplerotic enzyme from Corynebacterium glutamicum which replenishes oxaloacetate consumed during lysine and glutamic acid production in industrial fermentations. In particular, isolated nucleic acid molecules are provided encoding the pyruvate carboxylase protein. Pyruvate carboxylase polypeptides are also provided.Type: GrantFiled: December 23, 1998Date of Patent: January 9, 2001Assignee: Massachusetts Institute of TechnologyInventors: Anthony J. Sinskey, Philip A. Lessard, Laura B. Willis
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Patent number: 6171834Abstract: The invention provides isolated nucleic acid compounds encoding the stem peptide biosynthetic gene murI of Streptococcus pneumoniae. Also provided are vectors and transformed heterologous host cells for expressing the MurI enzyme product and a method for identifying compounds that inhibit stem peptide biosynthesis.Type: GrantFiled: April 30, 1999Date of Patent: January 9, 2001Assignee: Eli Lilly and CompanyInventors: Jo Ann Hoskins, Franklin Harpold Norris, Pamela Kay Rockey, Paul Robert Rosteck, Jr., Paul Luther Skatrud, Patti Jean Treadway, Michele Louise Young Bellido, Chyun-Yeh Earnest Wu
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Patent number: 6171835Abstract: The invention provides ribH polypeptides and polynucleotides encoding ribH polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing ribH polypeptides to screen for antibacterial compounds.Type: GrantFiled: August 30, 1999Date of Patent: January 9, 2001Assignees: SmithKline Beecham Corporation, SmithKline Beecham plcInventors: Michael Terence Black, Jason Craig Fedon, John Edward Hodgson, David Justin Charles Knowles, Michael Arthur Lonetto, Anna Lisa Kosmatka, Richard Oakley Nicholas, Leslie Marie Palmer, Lisa Kathleen Shilling, Robert King Stodola, Richard Lloyd Warren
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Patent number: 6171836Abstract: An expression cassette, operable in a recombinant host, comprising a heterologous DNA coding sequence encoding a protein, which is functional, alone or in cooperation with one or more additional proteins, of catalyzing an oxidation step in the biological pathway for conversion of cholesterol into hydrocortisone, which step is selected from the group consisting of: the conversion of cholesterol to pregnenolone; the conversion of pregnenolone to progesterone; the conversion of progesterone to 17&agr;-hydroxyprogesterone; the conversion of 17&agr;-hydroxyprogesterone to cortexolone; the conversion of cortexolone to hydrocortisone, and the corresponding control sequences effective in said host.Type: GrantFiled: June 17, 1998Date of Patent: January 9, 2001Assignee: Hoechst Marion RousselInventors: Herman Slijkhuis, Eric Bastiaan Smaal, Gerardus Cornelis Maria Selten
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Patent number: 6171837Abstract: This invention provides an isolated nucleic acid molecule (SEQ ID NO:1) encoding a human 9-cis-retinol dehydrogenase. Also provided is a 9-cis-retinol dehydrogenase encoded by the isolated nucleic acid molecule, wherein the 9-cis-retinol dehydrogenase comprises the amino acid sequence of SEQ. ID NO: 2. This invention also provides isolated nucleic acid molecules comprising the nucleotide sequence shown in any of SEQ. ID NOS: 6, 7, and 8 encoding mouse 9-cis-retinol dehydrogenases.Type: GrantFiled: September 29, 1997Date of Patent: January 9, 2001Assignee: The Trustees of Columbia University in the City of New YorkInventors: William S. Blaner, Roseann Piantedosi Zott, Mary V. Gamble, James R. Mertz
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Patent number: 6171838Abstract: The invention provides ratB polypeptides and DNA (RNA) encoding ratB polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing ratB polypeptides to screen for antibacterial compounds.Type: GrantFiled: August 13, 1997Date of Patent: January 9, 2001Assignee: SmithKline Beecham CorporationInventor: Michael Terence Black
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Patent number: 6171839Abstract: This invention relates to isolated nucleic acid fragments encoding all or a substantial portion of soybean (Glycine max) glutathione-S-transferase (GST) enzymes involved in the detoxification of xenobiotic compounds in plants and seeds; this invention further relates to isolated GST enzymes. The invention also relates to the construction of chimeric genes encoding all or a substantial portion of soybean GST enzymes, host cells transformed with those genes and methods for the recombinant production of soybean GST enzymes. Methods of constructing transgenic plants having altered levels of GST enzymes and screens for identifying soybean GST enzyme substrates and soybean GST enzyme inhibitors are also provided.Type: GrantFiled: April 22, 1999Date of Patent: January 9, 2001Assignee: E. I. du Pont de Nemours & CompanyInventors: Brian McGonigle, Daniel P. O'Keefe