Cephalosporin C Patents (Class 435/49)
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Patent number: 11865107Abstract: A composition comprising a therapeutically effective amount of at least one alkaloid combined with one or more non-alkaloid components, wherein the composition is configured to be administered to a subject.Type: GrantFiled: September 2, 2020Date of Patent: January 9, 2024Inventors: Gary Kompothecras, Michael Mullan, Daniel Paris
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Patent number: 8890121Abstract: A technique is provided for base recognition in an integrated device is provided. A target molecule is driven into a nanopore of the integrated device. The integrated device includes a nanowire separated into a left nanowire part and a right nanowire part to form a nanogap in between, a source pad connected to the right nanowire part, a drain pad connected to the left nanowire part, and the nanopore. The source pad, the drain pad, the right nanowire part, the left nanowire part, and the nanogap together form a transistor. The nanogap is part of the nanopore. A transistor current is measured while a single base of the target molecule is in the nanogap of the nanopore, and the single base affects the transistor current. An identity of the single base is determined according to a change in the transistor current.Type: GrantFiled: May 6, 2013Date of Patent: November 18, 2014Assignee: International Business Machines CorporationInventors: Shu-Jen Han, Ajay K. Royyuru, Gustavo A. Stolovitzky, Deqiang Wang
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Patent number: 8648184Abstract: The present invention relates to a zearalenone-inducible promoter originated from Gibberella zeae, recombinant vectors comprising the promoters, methods of producing proteins and detecting plants contaminated with zearalenone. The promoter of the present invention can be used for studying essential genes in fungus, characterizing the mechanism of self/nonself recognition in G. zeae, engineering of plant systems to generate plants that can recognize a G. zeae attack and detecting ZEA contamination as a biosensor.Type: GrantFiled: December 13, 2010Date of Patent: February 11, 2014Assignee: SNU R&DB FoundationInventors: Yin Won Lee, Jung Kwan Lee, Ae Ran Park, Seung Hoon Lee, Ho Kyung Son
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Patent number: 8557978Abstract: This invention provides cross-linked glycopeptide-cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.Type: GrantFiled: September 21, 2011Date of Patent: October 15, 2013Assignee: Theravance, Inc.Inventor: Daniel D. Long
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Oral care compositions containing combinations of anti-bacterial and host-response modulating agents
Patent number: 8283135Abstract: The present invention encompasses topical oral care compositions comprising the combination of an anti-bacterial agent with an anti-inflammatory agent in an orally acceptable carrier for effective treatment and prevention of bacteria-mediated diseases and conditions in the oral cavity and for modulating host reaction to bacterial pathogens present in the oral cavity and to the toxins, endotoxins, inflammatory cytokines and mediators released by or prompted by these pathogens. The present invention also encompasses methods of use of these compositions comprising topical application to the oral cavity. The benefits of the present compositions and methods extend beyond treating and preventing oral bacterial infections in the oral cavity to promoting whole body or systemic health.Type: GrantFiled: November 10, 2006Date of Patent: October 9, 2012Assignee: The Procter & Gamble CompanyInventors: Matthew Joseph Doyle, Leo Timothy Laughlin, Todd Laurence Underiner, Begonia Y. Ho, Rowan Andrew Grayling -
Patent number: 8044195Abstract: This invention provides cross-linked glycopeptide—cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.Type: GrantFiled: April 13, 2010Date of Patent: October 25, 2011Assignee: Theravance, Inc.Inventor: Daniel D. Long
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Patent number: 7955813Abstract: A method for the in situ production of an emulsifier in a foodstuff, wherein a lipid acyltransferase is added to the foodstuff. Preferably the emulsifier is produced without an increase or without a substantial increase in the free fatty acid content of the foodstuff. Preferably, the lipid acyltransferase is one which is capable of transferring an acyl group from a lipid to one or more of the following acyl acceptors: a sterol, a stanol, a carbohydrate, a protein or a sub-unit thereof, glycerol. Preferably, in addition to an emulsifier one or more of a stanol ester or a stanol ester or a protein ester or a carbohydrate ester or a diglyceride or a monoglyceride may be produced. One or more of these may function as an additional emulsifier.Type: GrantFiled: July 7, 2006Date of Patent: June 7, 2011Assignee: Danisco, A/SInventors: Arno De Kreij, Susan Mampusti Madrid, Jørn Dalgaard Mikkelsen, Jørn Borch Søe
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Patent number: 7884318Abstract: Systems, methods, and computer-readable media for determining composition of chemical constituents in a complex mixture are disclosed. According to one aspect, a method for determining composition of chemical constituents in a complex mixture includes generating, using a separation tool and a mass spectrometer, separation and mass spectrometry data of a sample, wherein the separation data includes peak information and wherein the mass spectrometry data includes primary and secondary mass spectrometry data. The analysis results, including the generated separation and mass spectrometry data, are collected and stored. A chemical constituent of the sample is determined by comparing the analysis results to a library of information indicating characteristics of chemical entities, where the comparison is based on the separation and mass spectrometry information.Type: GrantFiled: December 3, 2008Date of Patent: February 8, 2011Assignee: Metabolon, Inc.Inventors: K. Eric Milgram, Thomas Barrett, Anne M Evans
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Patent number: 7728127Abstract: This invention provides cross-linked glycopeptide-cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.Type: GrantFiled: August 24, 2007Date of Patent: June 1, 2010Assignee: Theravance, Inc.Inventors: Paul R. Fatheree, Martin S. Linsell, Daniel Marquess, S. Derek Turner
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Patent number: 7713931Abstract: This invention provides cross-linked glycopeptide-cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.Type: GrantFiled: August 24, 2007Date of Patent: May 11, 2010Assignee: Theravance, Inc.Inventors: Paul R. Fatheree, Martin S. Linsell, Daniel Marquess, S. Derek Turner
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Patent number: 7655621Abstract: This invention provides cross-linked glycopeptide-cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.Type: GrantFiled: August 24, 2007Date of Patent: February 2, 2010Assignee: Theravance, Inc.Inventors: Paul R. Fatheree, Martin S. Linsell, Daniel Marquess, S. Derek Turner
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Patent number: 7649080Abstract: This invention provides cross-linked glycopeptide-cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.Type: GrantFiled: August 24, 2007Date of Patent: January 19, 2010Assignee: Theravance, Inc.Inventors: Paul R. Fatheree, Martin S. Linsell, Daniel Marquess, S. Derek Turner
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Patent number: 7612037Abstract: This invention provides cross-linked glycopeptide-cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.Type: GrantFiled: October 25, 2007Date of Patent: November 3, 2009Assignee: Theravance, Inc.Inventors: Paul R. Fatheree, Martin S. Linsell, Daniel D. Long, Daniel Marquess, Edmund J. Moran, Matthew B. Nodwell, S. Derek Turner, James Aggen
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Patent number: 7601690Abstract: This invention provides cross-linked glycopeptides—cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.Type: GrantFiled: August 24, 2007Date of Patent: October 13, 2009Assignee: Theravance, Inc.Inventors: Paul R. Fatheree, Martin S. Linsell, Daniel Marquess, S. Derek Turner
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Patent number: 7553635Abstract: The present invention relates to isolated nucleic acid molecules which code for a new protein from Acremonium chrysogenum, to vectors which comprise such a nucleic acid molecule, to Acremonium chrysogenum host cells which have been transformed with such a vector and to a method for production of cephalosporin C using such transformed host cells.Type: GrantFiled: September 16, 2003Date of Patent: June 30, 2009Assignee: Sandoz AGInventors: Hubert Kürnsteiner, Ernst Friedlin
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Patent number: 7288386Abstract: A method of determining the presence of soybean sudden death syndrome resistance in the soybean plant in a greenhouse setting, the method comprising the steps of: (a) inoculating soil with a low density inoculum of Fusarium solani; (b) planting a soybean plant in said inoculated soil; (c) growing said plant in said soil in a greenhouse; (d) isolating Fusarium solani-infected tissue from said plant; (e) culturing said infected tissue for a period of time sufficient to allow for fungal colony forming unit growth; (f) scoring at least one of disease severity and infection severity in said plant using the number of said fungal colony forming units; and (g) correlating at least one of said disease severity and said infection severity to at least one of disease severity and infection severity data from genetic markers associated with soybean sudden death syndrome resistance to identify a correlation, wherein a statistically significant correlation indicates presence of soybean sudden death syndrome resistance in saType: GrantFiled: September 18, 2001Date of Patent: October 30, 2007Assignee: Southern Illinois UniversityInventors: David A. Lightfoot, Paul T. Gibson, Khalid Meksem
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Patent number: 7211377Abstract: Method for the detection of dormant cryptobiotic microbes by detection of electromagnetic radiation emitted from intrinsic alkali earth metal pyridine dicarboxylic acid salts in the 710 nm to 860 nm region when excited with electromagnetic energy in the 610 nm to 680 nm region. Utilizing the novel lower energy emission of intrinsic calcium dipicolinic acid salts makes it possible to quickly detect bacterial spores, fungal spores and oocysts without the need for any added reagents, sample processing, or contact with the sample.Type: GrantFiled: April 2, 2004Date of Patent: May 1, 2007Assignee: Microbiosystems, Limited PartnershipInventors: Linda S. Powers, Christopher R. Lloyd
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Patent number: 6913901Abstract: Procedure for controlling the enumeration of the absolute count of cells (or other particles) present in a sample.Type: GrantFiled: February 14, 2002Date of Patent: July 5, 2005Assignee: Universidad de SalamancaInventor: José Alberto Orfao de Matos Correia e Vale
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Patent number: 6750006Abstract: Method and apparatus for the detection of microbes in liquids, in air and on non-living surfaces in which samples are exposed to electromagnetic radiation of specific energies capable of exciting various metabolites, cofactors and cellular and spore components, with the microbial cells to be sampled (and more specifically the excited metabolites, cofactors and or other cellular components) contained therein emit fluorescence that can be measured. The signal from the background and scattered excitation signals is removed from the fluorescence signals of the microbial components, the relative fluorescent signals of the intrinsic microbial components are required to lie within physiological ranges, and the amplitude of the background-corrected fluorescence signals used to enumerate the microbe content in the sample.Type: GrantFiled: January 22, 2002Date of Patent: June 15, 2004Assignee: Microbiosystems, Limited PartnershipInventors: Linda S. Powers, Christopher R. Lloyd
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Publication number: 20040009608Abstract: A method of fabricating an array of different chemical moieties. The method may include ejecting drops containing the different moieties or precursors thereof from an orifice in an ejector head onto a substrate surface spaced from the orifice so as to form the array. The substrate surface may have structures adjacent each of multiple feature locations so as to assist in confining drops ejected onto the surface to the feature locations, which structures comprise channels or deposited raised members adhering to the surface and extending above adjacent feature locations. An array of different chemical moieties is also provided which has features at respective locations on a planar substrate surface having structures comprising channels or deposited raised barriers adhering to the surface, and which structures are adjacent each of multiple feature locations.Type: ApplicationFiled: July 10, 2002Publication date: January 15, 2004Inventors: Michael P. Caren, William D. Fisher, Peter G. Webb
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Patent number: 6642020Abstract: An enzymatic process for preparing 3-thiolated 7-aminocephalosporanic acid derivatives comprises the steps of enzymatically converting a 3-thiolated cephalosporin C of the formula I: to form a 3-thiolated-glutaryl-7-ACA of the formula II and enzymatically converting a compound of formula II to form a 3-thiolated-7-ACA of the formula III wherein R is a heterocyclic group comprising at least one nitrogen atom and R1 and R2 are both hydrogen atoms or one of them is a hydrogen atom and the other is an acyl donor.Type: GrantFiled: April 19, 2002Date of Patent: November 4, 2003Assignee: Bioferma Murcia S.A.Inventors: Álvaro Sánchez-Ferrer, José Aniceto López-Más, Francisco Garcia-Carmona
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Patent number: 6630338Abstract: An enzyme in a mixture containing the enzyme and a contaminant enzyme is purified by selectively aggregating and precipitating the contaminant enzyme with a surfactant. A deacetylase contaminant is separated from Cephalosporin C acylase using a cationic surfactant in an amount of 0.1 to 0.6%. Surfactants include benzylated or methylated cationic surfactants such as alkyl(palm)dimethylbenzyl ammonium chloride, alkyl(palm)trimethyl ammonium chloride and dodecyltrimethyl ammonium chloride. An immobilized enzyme is regenerated using a protease to remove the enzyme from a carrier. The carrier may be a synthetic adsorbent or an ion exchange resin having pores of 100 nm or less in diameter, and the immobilized enzyme is optionally crosslinked. Immobilized cephalosporin C acylase is regenerated using an alkaline or acidic protease.Type: GrantFiled: May 9, 2000Date of Patent: October 7, 2003Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventor: Katsushi Asai
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Patent number: 6503727Abstract: The invention relates to a process for the preparation of an antibiotic, in particular cefalexin, ampicillin, amoxicillin, cefaclor, cefradin, cefadroxil, cefotaxim and the like, wherein a beta-lactam core is acylated, the antibiotic is recovered from the reaction mixture, the remaining mother liquor is subjected to a hydrolysis reaction in which the antibiotic present in the mother liquor is decomposed into its initial compounds, in particular the beta-lactam core, and the acylation agent is hydrolized. The beta-lactam core can then be recovered virtually quantitatively or recycled to the acylation reaction. This is because it has been found that the solubility of the beta-lactam core is unexpectedly high at relatively high concentrations of acylation agent and antibiotic.Type: GrantFiled: June 5, 1998Date of Patent: January 7, 2003Assignee: Gist-Brocades, B.V.Inventors: Wilhelmus H. J. Boesten, Wilhelmus J. J. Van Den Tweel, Rocus M. Dekkers
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Patent number: 6410259Abstract: The present invention disclosures a process for the production of N-deacylated cephalosporin compounds via the fermentative production of their 7-acylated counterparts.Type: GrantFiled: August 26, 1999Date of Patent: June 25, 2002Assignee: DSM Patents & TrademarksInventors: Maarten Nieboer, Erik De Vroom, Johannis Lugtenburg, Dirk Schipper, Adrianus Wilhelmus Hermanus Vollebregt, Roelof Ary Lans Bovenberg
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Patent number: 6383773Abstract: The present invention provides a biological system for expanding the dethiazolidine ring of penicillins into the dehydrothiazine ring of cephalosporins or cephalosporin precursors. In particular, the invention defines reaction conditions under which expandase enzyme can convert penicillin substrates other than penicillin N into cephalosporins. The invention therefore provides a relatively inexpensive, uncomplicated, and environmentally friendly biological system for cephalosporin production from penicillins, which system can replace the synthetic chemical approaches currently utilized. In particular, the invention provides a system for producing DOAG and/or DAG, which can be enzymatically converted into 7-ADCA and 7-ADAC, which, in turn, can be enzymatically or chemically converted into valuable cephalosporins of commerce.Type: GrantFiled: April 22, 1999Date of Patent: May 7, 2002Assignee: Massachusetts Institute of TechnologyInventors: Arnold L. Demain, Hiroshi Cho, Jacqueline M. Piret, Josè L. Adrio, Maria-Josefa E. Fernandez, Marco A. Bàez-Vàsquez, Gilberto Hintermann
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Patent number: 6368820Abstract: An improved process for production of an N-acylated cephalosporin is described. The process utilizes an Acremonium strain which has been modified to express an acyl transferase of a filamentous fungus and is selected for production of the N-acylated cephalosporin at a level which is equal to or higher than the production of the corresponding &agr;-aminoadipyl-7-cephalosporins in the strain.Type: GrantFiled: January 15, 1999Date of Patent: April 9, 2002Assignee: DSM N.V.Inventors: Roelof Ary Lans Bovenberg, Dirk Schipper, Richard Kerkman
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Publication number: 20020037547Abstract: The present invention discloses a process for the production of N-deacylated cephalosporin compounds via the fermentative production of their 7-acylated counterparts.Type: ApplicationFiled: May 17, 1999Publication date: March 28, 2002Inventors: MAARTEN NIEBOER, ERIK DE VROOM, JOHANNIS LUGTENBURG, DIRK SCHIPPER, ADRIANUS WILHELMUS H VOLLEBREGT, ROELOF ARY LANS BOVENBERG
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Patent number: 6319684Abstract: The present invention relates to a novel process for the preparation of cephalosporins having been deacylated at the 7-amino group, by fermentation of a cephalosporin producing microorganism in the presence of a side chain precursor, extraction of the N-substituted cephalosporin compound as present in the fermentation broth or fluid to an organic solvent, back extraction of the N-substituted cephalosporin compound to water, treatment of the aqueous phase with a dicarboxylate acylase and isolation of the crystalline cephalosporin compound according to formula (1) from the conversion solution, characterized in that the fermentation broth or fluid is incubated at acidic conditions and an elevated temperature prior to extraction of the N-substituted cephalosporin compound to an organic solvent.Type: GrantFiled: August 26, 1999Date of Patent: November 20, 2001Assignee: DMS N.V.Inventors: John Krijgsman, Jan Willem Hubert Smeets, Henriëtte Elisabeth Anna De Braal, Erik De Vroom, Herman Pieter Fasel
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Publication number: 20010014463Abstract: A method for the treatment and prevention of dental caries and periodontal diseases using bacteriophages and phage-encoded anti-bacterial enzymes to inhibit establishment of bacteria in the oral cavity is provided. Also provided are methods for studying the cell wall of an oral bacterium, a method for preventing spoilage of perishable items and a method for removing dextrans from surfaces utilized in sugar manufacture. Purified enzymes and the isolated DNA fragments encoding them are also provided.Type: ApplicationFiled: June 30, 1997Publication date: August 16, 2001Inventor: ALLAN L. DELISLE
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Publication number: 20010006795Abstract: The present invention provides a biological system for expanding the dethiazolidine ring of penicillins into the dehydrothiazine ring of cephalosporins or cephalosporin precursors. In particular, the invention defines reaction conditions under which expandase enzyme can convert penicillin substrates other than penicillin N into cephalosporins. The invention therefore provides a relatively inexpensive, uncomplicated, and environmentally friendly biological system for cephalosporin production from penicillins, which system can replace the synthetic chemical approaches currently utilized. In particular, the invention provides a system for producing DOAG and/or DAG, which can be enzymatically converted into 7-ADCA and 7-ADAC, which, in turn, can be enzymatically or chemically converted into valuable cephalosporins of commerce.Type: ApplicationFiled: April 22, 1999Publication date: July 5, 2001Inventors: ARNOLD L. DEMAIN, HIROSHI CHO, JACQUELINE M. PIRET, JOSE L. ADRIO, MARIA-JOSEFA E. FERNANDEZ, MARCO A. BAEZ-VASQUEZ, GILBERTO HINTERMANN
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Patent number: 6180360Abstract: The present invention relates to the biosynthesis of &bgr;-lactam antibiotics. More specifically, the invention relates to processes of producing &bgr;-lactam antibiotics in vivo and in vitro. Also contemplated is a novel enzyme capable of catalyzing certain steps involved in &bgr;-lactam biosynthesis. Further, the invention relates to a DNA construct encoding the novel enzyme, a recombinant vector or transformation vehicle comprising the DNA construct, and finally a cell comprising the DNA construct or recombinant vector.Type: GrantFiled: June 15, 1999Date of Patent: January 30, 2001Assignee: Gist-BrocadesInventors: Svend Kaasgaard, Klaus Kristiansen, Henrik Mølgaard
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Patent number: 6165758Abstract: An enzyme in a mixture containing the enzyme and a contaminant enzyme is purified by selectively aggregating and precipitating the contaminant enzyme with a surfactant. A carrier containing an immobilized enzyme is regenerated by using a protease to remove the enzyme from the carrier. Cephalosporin C acylase is purified from a mixture of the acylase and a deacetylase contaminant by selectively aggregating and precipitating the deacetylase contaminant by adding to the solution a benzylated cationic or methylated cationic surfactant in an amount of 0.1 to 0.6% of the mixture. The surfactant may be alkyl(palm)dimethylbenzyl ammonium chloride. A carrier containing immobilized cephalosporin C acylase is regenerated by contacting the carrier with an alkaline or acidic protease. The acylase is immobilized by being bound to the carrier and optionally crosslinked. The carrier may have pores of 100 nm or less in diameter.Type: GrantFiled: February 12, 1999Date of Patent: December 26, 2000Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventor: Katsushi Asai
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Patent number: 6071713Abstract: A bioprocess for preparing adipoyl-7-ACA comprising the steps: (a) transforming cells of a strain of Penicillium chrysogenum which produces isopenicillin N with an expression vector containing DNA encoding an enzyme, having expandase activity capable of accepting adipoyl 6-APA as a substrate, an enzyme having hydroxylase activity capable of accepting adipoyl-7-ADCA as a substrate and an enzyme having acetyl transferase activity capable of accepting adipoyl 7-ADAC as a substrate; (b) culturing the transformed cells from step a) in a suitable culture medium containing an adipate feedstock, wherein said cells produce adipoyl 6-APA; and (c) culturing the transformed cells producing adipoyl 6-APA of step b) under conditions suitable for expression of said DNA encoding enzyme, thereby producing the end product adipoyl-7-ACA.Type: GrantFiled: June 28, 1999Date of Patent: June 6, 2000Assignee: Gist-Brocades B.V.Inventors: Michael J. Conder, John A. Rambosek, Phyllis C. McAda, Christopher D. Reeves
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Patent number: 5942411Abstract: The present invention relates to the biosynthesis of .beta.-lactam antibiotics. More specifically, the invention relates to processes of producing .beta.-lactam antibiotics in vivo and in vitro. Also contemplated is a novel enzyme capable of catalyzing certain steps involved in .beta.-lactam biosynthesis. Further, the invention relates to a DNA construct encoding the novel enzyme, a recombinant vector or transformation vehicle comprising the DNA construct, and finally a cell comprising the DNA construct or recombinant vector.Type: GrantFiled: June 19, 1997Date of Patent: August 24, 1999Assignee: Gist-BrocadesInventors: Svend Kaasgaard, Klaus N. Kristiansen, Henrik M.o slashed.lgaard
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Patent number: 5919680Abstract: An overall process for the preparation and recovery of 7-aminodesacetoxycephalosporanic acid (7-ADCA) via enzymatic ring expansion activity on penicillin G, using a Penicillium chrysogenum transformant strain expressing modified expandase enzyme.Type: GrantFiled: November 27, 1996Date of Patent: July 6, 1999Assignee: Isis Innovation LimitedInventors: John David Sutherland, Roelof Ary Lans Bovenberg, Jan Metske van der Laan
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Patent number: 5804429Abstract: A mutant CC acylase wherein at least one amino acid at the Ala.sup.49, Met.sup.164, Ser.sup.166, Met.sup.174, Glu.sup.358, Met.sup.465, Met.sup.506, or Met.sup.750 position of the amino acid sequence of the native CC acylase is replaced by a different amino acid, a DNA coding therefor, an expression vector containing the said DNA, a microorganism transformed with the said expression vector, the production of the CC acylase by culturing the said transformant, and use thereof for the production of a compound. The mutant CC acylase of the invention has desirable properties in terms of enzymatic potency, alteration of pH profile, efficiency of processing, and the like.Type: GrantFiled: May 1, 1996Date of Patent: September 8, 1998Assignee: Fujisawa Pharmaceutical Co., Ltd.Inventors: Mineo Niwa, Yoshimasa Saito, Takao Fujimura, Yoshinori Ishii, Yuji Noguchi
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Patent number: 5780260Abstract: An enzyme selected from penicillin-G amidase, glutaryl-7-ACA acylase and D-amino acid oxidase is immobilized by covalent bonding on an aminofunctional organosiloxane polymer carrier to provide an immobilized enzyme having a specific volume activity of at least 100 U/g wet carrier. Preferably, the carrier has an average diameter or 0.01 to 3 mm and is essentially spherical. Covalent bonding is accomplished by activating amino groups on the carrier with a dialdehyde and reacting the activated groups with reactive groups on the enzyme. An amount of enzyme is immobilized to provide a weight ratio of enzyme to carrier of 1 to 300 mg protein per g wet carrier.Type: GrantFiled: May 30, 1996Date of Patent: July 14, 1998Assignee: Boehringer Mannheim GmbHInventors: Frank Wedekind, Adelheid Daser, Wilhelm Tischer
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Patent number: 5753458Abstract: A method for providing a semisynthetic .beta.-lactam antibiotic by enzyme catalyzed acylation of the parent .beta.-lactam with an activated derivative of the side chain acid wherein a modulator, which consists of one or more compounds different from the reactants and the reaction product and which suppresses the hydrolysis of the activated derivative of the side chain acid and the desired product more than it suppresses the synthesis of the desired product, is added to the reaction mixture, at the beginning of the reaction process, in a concentration from about 0.2 to 100.times.10.sup.3 .mu.m.Type: GrantFiled: February 7, 1996Date of Patent: May 19, 1998Assignee: Gist-Brocades B.V.Inventors: Kim Clausen, Annette Nielsen, Niels Petersen, Alexander Nikolov
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Patent number: 5726032Abstract: An overall efficient process for the preparation and recovery of 7-aminodesacetoxycephalosporanic acid (7-ADCA) via 2-(carboxyethylthio)acetyl- and 3-(carboxymethylthio)propionyl-7-ADCA, using a Penicillium chrysogenum transformant strain expressing expandase in conjunction with acyltransferase, is provided.Type: GrantFiled: April 4, 1996Date of Patent: March 10, 1998Assignee: Gist-Brocades B.V.Inventors: Roelof Ary Lans Bovenberg, Bertus Pieter Koekman, Andreas Hoekema, Jan Metske Van Der Laan, Jan Verweij, Erik De Vroom
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Patent number: 5629171Abstract: Important intermediates for preparing cephalosporin antibiotics, 7-amino-cephalosporanic acid (7-ACA) and 7-aminodeacetylcephalosporanic acid (7-ADAC), are prepared by a novel bioprocess in which a transformed Penicillium chrysogenum strain is cultured in the presence of an adipate feedstock to produce adipoyl-6-APA (6-amino penicillanic acid); followed by the in situ expression of the following genes with which the P. chrysogenum has been transformed:1) an expandase gene, whose expression product converts the adipoyl-6-APA by ring expansion to adipoyl-7-ADCA;2) an hydroxylase gene whose expression product converts the 3-methyl side chain of adipoyl-7-ADCA to 3-hydroxymethyl, to give the first product, 7-aminodeacetylcephalosporanic acid (7-ADAC); and3) an acetyltransferase gene whose expression product converts the 3-hydroxymethyl side chain to the 3-acetyloxymethyl side chain of 7-ACA. The final product, 7-ACA, is then prepared by cleavage of the adipoyl side chain using an adipoyl acylase.Type: GrantFiled: May 11, 1995Date of Patent: May 13, 1997Assignee: Gist-Brocades B.V.Inventors: Michael J. Conder, John A. Rambosek, Phyllis C. McAda, Christopher D. Reeves
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Patent number: 5599702Abstract: D-amino acid oxidase (DAO) in purified, partially purified or crude form is immobilized on a porous bead-shaped support that is a copolymer of vinyl acetate and/or vinyl alcohol and a crosslinking agent. A preferred crosslinking agent is N,N'-divinylethyleneurea. The amount of crosslinking agent is 1 to 60% by weight of the copolymer, and acyloxy groups of vinyl acetate may be present on the support as such or may have been hydrolyzed to hydroxyl groups. The support preferably has a mean particle size of 20 to 800 .mu.m and a mean pore diameter of 2 to 10,000 nm. The D-amino acid oxidase is preferably obtained from Trigonopsis variabilis and purified by ion exchange chromatography. The D-amino acid oxidase may be covalently bonded to a spacer such as epichlorohydrin or its homolog that is bound to the support. Catalase may also be immobilized.Type: GrantFiled: May 17, 1995Date of Patent: February 4, 1997Assignee: Hoechst AktiengesellschaftInventor: Klaus Sauber
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Patent number: 5597704Abstract: A method of converting cephalosporin C to glutaryl-7-aminocephalosporanic acid. The method including obtaining a cell preparation from a microorganism which produces D-amino acid oxidase, the preparation being a cell-free extract or a suspension of permeated cells; adding a D-.alpha.-amino acid to the preparation; after the adding step, heating the preparation at 50.degree.-75.degree. C. for 5-60 minutes; and incubating cephalosporin C in the preparation. Also disclosed are a method of converting cephalosporin C to glutaryl-7-aminocephalosporanic acid in the absence of exogenous H.sub.2 O.sub.2, and a method of screening for a D-amino acid oxidase-producing microorganism.Type: GrantFiled: May 1, 1995Date of Patent: January 28, 1997Assignee: Food Industry Research and Development InstituteInventors: Yun-Huey Lee, Wen-Shen Chu, Wen-Hwei Hsu
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Patent number: 5559005Abstract: Important intermediates for preparing cephalosporin antibiotics, 7-amino-cephalosporanic acid (7-ACA) and 7-aminodeacetylcephalosporanic acid (7-ADAC), are prepared by a novel bioprocess in which a transformed Penicillium chrysogenum strain is cultured in the presence of an adipate feedstock to produce adipoyl-6-APA (6-amino penicillanic acid); followed by the in situ expression of the following genes with which the P. chrysogenum has been transformed:1) an expandase gene, e.g., from Cephalosporium acremonium, whose expression product converts the adipoyl-6-APA by ring expansion to adipoyl-7-ADCA;2) an hydroxylase gene whose expression product converts the 3-methyl side chain of adipoyl-7-ADCA to 3-hydroxymethyl, to give the first product, 7-aminodeacetylcephalosporanic acid (7-ADAC); and3) an acetyltransferase gene whose expression product converts the 3-hydroxymethyl side chain to the 3-acetyloxymethyl side chain of 7-ACA.Type: GrantFiled: May 27, 1994Date of Patent: September 24, 1996Assignee: Merck & Co., Inc.Inventors: Michael J. Conder, Phyllis C. McAda, John A. Rambosek, Christopher D. Reeves
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Patent number: 5514561Abstract: Chromogenic and fluorogenic substrates for .beta.-lactamase, methods for synthesis thereof and methods for detecting .beta.-lactamase in a sample are provided. The substrates are substantially colorless or substantially nonfluorescent .beta.-lactam compounds which include an electronegative leaving group. The leaving group comprises a carbamate, carbonate, thiocarbamate or thiocarbonate linkage and a fluorescent moiety or a moiety capable of producing a visually detectable colored product. Upon cleavage of the lactam ring by .beta.-lactamase, the leaving group is liberated and fluorescence or a colored product is produced.Type: GrantFiled: April 14, 1994Date of Patent: May 7, 1996Assignee: Becton, Dickinson and CompanyInventors: J. Michael Quante, Randal A. Hoke, Patrick D. Mize, Daniel L. Woodard, O. Elmo Millner, deceased
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Patent number: 5512454Abstract: O-acylated cephalosporins are produced by reacting 3-hydroxymethylcephalosporins with an acyl donor containing at least three carbon atoms and an enzyme which is a Rodosporidium toruloides esterase, a wheat germ lipase, an Aspergillus niger lipase, an orange peel acetylesterase or a Bacillus subtilis esterase. A preferred enzyme is the esterase from Rodosporidium toruloides ATCC 10657. The enzyme can be used while in whole cells or in soluble or inmobilized form.Type: GrantFiled: February 3, 1994Date of Patent: April 30, 1996Assignee: Bristol-Myers Squibb CompanyInventors: John J. Usher, Guna Romancik, Michael Politino, David A. Lowe
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Patent number: 5474912Abstract: Targeted gene insertion methodology can increase the production of an antimicrobial metabolite and comprises the steps of:a) identifying the gene in unaltered chromosomal DNA which encodes an enzyme that catalyzes the rate controlling step in a biosynthetic pathway in the production of increased concentration of a precursor to a core molecule which leads to the antimicrobial metabolite; andb) inserting into unaltered chromasomal DNA a genetic delivery vehicle (such as a vector, phage, or virus) which carries a gene which encodes the enzyme that catalyzes the rate controlling step in the biosynthesis in the production of a core molecule which is a precursor to the antimicrobial metabolite into unaltered chromosomal DNA, said delivery vehicle being compatible with said unaltered chromosomal DNA, the delivery vehicle being generated byinserting at least one exact or modified copy of the gene determining the rate controlling step into the compatible delivery vehicle, andinserting the delivery vehicle containing tType: GrantFiled: March 3, 1994Date of Patent: December 12, 1995Inventors: David H. Sherman, Wei-Shou Hu, Li-Hong Malmberg
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Patent number: 5466598Abstract: A DNA is disclosed, which comprises a gene coding for deacetylcephalosporin C acetyltransferase, i.e., an enzyme capable of catalyzing the final step of the biosynthesis of cephalosporin C. The gene may be either a cDNA or a genomic DNA. Also disclosed is a recombinant DNA comprising a vector having inserted therein at least a portion of the above-mentioned DNA, which recombinant DNA is in a form such that the portion is capable of expression in Acremonium chrysogenum. Acremonium chrysogenum transformed with the recombinant DNA can be advantageously used for efficiently preparing cephalosporin C.Type: GrantFiled: January 7, 1994Date of Patent: November 14, 1995Assignee: Asahi Kasei Kogyo Kabushiki KaishaInventors: Akio Matsuda, Kenji Matsuyama
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Patent number: 5453374Abstract: A Trigonopsis variabilis transformed with a recombinant DNA containing a D-amino acid oxidase gene capable of expressing in Trigonopsis variabilis is provided. A process for transforming Trigonopsis variabilis and a process for preparing 7-.beta.-(5-carboxy-5-oxopenetaneamide)cephalosporanic acid by using a transformant of Trigonopsis variabilis are also provided. The transformant of Trigonopsis variabilis shows high DAO activity and low activity of an esterase which interferes with the preparation of cephalosporin C. Accordingly, the Trigonopsis variabilis of the present invention enables one to produce cephalosporin C.Moreover, the Trigonopsis variabilis of the present invention can be used for the preparation or cephalosporin C merely by treating the cells with toluene so that large scale use is practical.Type: GrantFiled: July 23, 1993Date of Patent: September 26, 1995Assignee: Asahi Kasai Kogyo Kabushiki KaishaInventors: Kaoru Furuya, Akio Matsuda
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Patent number: 5356781Abstract: Pancreatic disease can be diagnosed by assaying a patient's body fluid such as serum or urine, for pancreatic activation peptides (PAP) released from zymogens by proteolytic activation. Particularly useful are peptides having C-terminal D.sub.4 K sequences. The method uses polyclonal or monoclonal antibodies generated and selected for C-terminal specificity on PAP so that the tests only report free PAP not parent zymogen. Also described are peptides and antibodies labelled with revealing agents and/or immobilised on solid supports and their use in diagnostic assays and kits. In pancreatic disease the tests distinguish necrotising from oedematous acute pancreatitis and permit severity prediction and monitoring as well as diagnosing chronic pancreatitis in exacerbation.Type: GrantFiled: June 26, 1991Date of Patent: October 18, 1994Assignee: Bioscience International, Inc.Inventors: John Hermon-Taylor, Brian M. Austen
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Patent number: 5350680Abstract: A cephalosporinase testing agent comprising a cephalosporin antibiotic, a penicillinase inhibitor in an amount of 20% by weight or less based on the weight of the cephalosporin-antibiotic, and a pH indicator which may be bromcresol purple is provided. A cephalosporinase producing bacteria can be judged by smearing a sample containing bacteria to be tested on the testing agent and observing the color tone change. According to this agent, cephalosporinase-active penicillinase producing bacteria are judged cephalosporinase-negative owing to the action of the penicillinase inhibitor, which may be clavulanic acid. Therefore, since only cephalosporinase producing bacteria are judged cephalosporinase-positive, this agent enables error free judgment.Type: GrantFiled: February 2, 1993Date of Patent: September 27, 1994Assignee: Showa Yakuhin Kako Co., Ltd.Inventors: Matsuhisa Inoue, Akira Sakai