By Desacylation Of The Substituent In 6-position Patents (Class 435/44)
  • Patent number: 11214786
    Abstract: The present invention provides engineered penicillin G acylase (PGA) enzymes having improved properties, polynucleotides encoding such enzymes, compositions including the enzymes, and methods of using the enzymes.
    Type: Grant
    Filed: June 15, 2020
    Date of Patent: January 4, 2022
    Assignee: Codexis, Inc.
    Inventors: Jovana Nazor, Vesna Mitchell, David Elgart, Katrina W. Lexa, Nikki Dellas, Robert Kevin Orr, Oscar Alvizo, Ravi David Garcia, Judy Victoria Antonio Viduya, Courtney Dianne Moffett
  • Patent number: 10829510
    Abstract: The present invention discloses a method for preparing sucralose-6-acetate in a biphasic liquid-liquid system. The method comprises slowly dropwise adding an inert non-polar solvent containing a chlorinating agent to an N,N-dimethyl formamide (DMF) solution of sucrose-6-acetate; then reacting the biphasic liquid-liquid mixture at a certain temperature for 9-20 hours; cooling the system to room temperature after stopping heating, and settling the solution to form layers, an upper layer being an inert non-polar solvent layer, and a lower layer being a DMF solution layer containing the product; hydrolyzing, neutralizing, and filtering the lower layer to obtain a filtrate, and then concentrating the filtrate to obtain a concentrate; dissolving the concentrate in water, and obtaining the product by extraction using ethyl acetate and crystallization, the inert non-polar solvent being an alkane solvent containing 8-18 carbon atoms that is not mutually soluble with DMF.
    Type: Grant
    Filed: May 18, 2017
    Date of Patent: November 10, 2020
    Assignee: ZHEJIANG NHU COMPANY LTD.
    Inventors: Fuxiang Deng, Yu Ding, Wei Xue, Sheng Yu, Wenwu Yan, Ming Yu, Yougui Zhou, Haoran Li
  • Patent number: 8889373
    Abstract: Enzyme catalyst immobilized on porous fluoropolymer supports. Catalytically active enzymes can be bound to a variety of fluoropolymer supports for use as a reaction catalyst. Moreover, consistently high rate of conversion during catalyst re-use over time is achieved. Furthermore, inactive enzyme catalyst can be stripped from the support and fresh enzyme can be bound to the support to achieve the original conversion rate. The immobilization of catalytic enzymes on porous fluoropolymers is a viable and novel technology for the preparation of advantaged catalysts.
    Type: Grant
    Filed: August 12, 2010
    Date of Patent: November 18, 2014
    Assignee: Eastman Chemical Company
    Inventor: Stephanie Kay Clendennen
  • Patent number: 8569013
    Abstract: The present disclosure relates to engineered penicillin G acylase (PGA) enzymes having improved properties, polynucleotides encoding such enzymes, compositions including the enzymes, and methods of using the enzymes.
    Type: Grant
    Filed: July 6, 2012
    Date of Patent: October 29, 2013
    Assignee: Codexis, Inc.
    Inventors: Behnaz Behrouzian, Anke Krebber, Emily Mundorff
  • Patent number: 8247192
    Abstract: The present disclosure relates to engineered penicillin G acylase (PGA) enzymes having improved properties, polynucleotides encoding such enzymes, compositions including the enzymes, and methods of using the enzymes.
    Type: Grant
    Filed: November 9, 2009
    Date of Patent: August 21, 2012
    Assignee: Codexis, Inc.
    Inventors: Behnaz Behrouzian, Anke Krebber, Emily Mundorff
  • Patent number: 8187610
    Abstract: The invention provides Streptococcus vaccine strains (e.g. S. equi which is causative of ‘strangles’) comprising the following modifications in their genomes: (i) attenuation of one or more essential biosynthetic genes, (ii) attenuation of one or more genes which encode a haemolytic toxin, or protein involved in the production thereof, plus preferably any one, two, or most preferably three of the following modifications: (iii) attenuation of one or more genes which encode a protein responsible for immune evasion (iv) modification of one or more genes such as to permit serological discrimination of the vaccine strain based on analysis of a protein encoded by said genes, and (v) attenuation of one or more genes which encode an enzyme responsible for recombination repair of the genome. The invention provides inter alia live attenuated vaccine strains which generate an immune response to multiple protective epitopes presented in a context resembling the live pathogen.
    Type: Grant
    Filed: January 20, 2009
    Date of Patent: May 29, 2012
    Assignee: Animal Health Trust
    Inventors: Andrew Stephen Waller, Carl Robinson, Zoe Heather
  • Patent number: 8114645
    Abstract: The present invention provides methods of increasing production of an isoprenoid or an isoprenoid precursor in a host cell, the methods generally involving modulating the level of activity of a fatty acid biosynthetic pathway enzyme in the host cell and/or culturing the host cell in a culture medium comprising a fatty acid or a compound that can be metabolized in a cell or broken down in the medium to yield a fatty acid and/or culturing the host cell in a culture medium having increased osmolarity.
    Type: Grant
    Filed: May 17, 2007
    Date of Patent: February 14, 2012
    Assignee: The Regents of the University of California
    Inventors: Douglas J. Pitera, Jack D. Newman, Jeffrey Lance Kizer, Jay D. Keasling, Brian F. Pfleger
  • Publication number: 20100143968
    Abstract: The present disclosure relates to engineered penicillin G acylase (PGA) enzymes having improved properties, polynucleotides encoding such enzymes, compositions including the enzymes, and methods of using the enzymes.
    Type: Application
    Filed: November 9, 2009
    Publication date: June 10, 2010
    Applicant: CODEXIS, INC.
    Inventors: BEHNAZ BEHROUZIAN, ANKE KREBBER, EMILY MUNDORFF
  • Patent number: 6770455
    Abstract: The present invention relates to metal-containing ribonucleotide polypeptides (RNP) and processes for their production, their use and medicaments containing ribonucleotide polypeptides or their molecular-biological equivalent structures and/or parts and/or derivatives.
    Type: Grant
    Filed: January 16, 2001
    Date of Patent: August 3, 2004
    Assignee: Fraunhofer
    Inventors: Stefan Kiesewetter, Eckehard Kuhn, Bridgitte Koch-Pelster, Herwig Brunner
  • Publication number: 20040053912
    Abstract: The invention relates to a process for the preparation of an aqueous solution or suspension of a &bgr;-lactam nucleus and application thereof. The aqueous solution or suspension of the &bgr;-lactam nucleus is prepared by process wherein an enzymatic deacylation of a &bgr;-lactam compound, which compounds comprises a &bgr;-lactam nucleus with a side chain coupled to it via an amide bond and which deacylation reaction is carried out in a mixture of water and an organic solvent and which deacylation leads to a &bgr;-lactam nucleus and a carboxylic acid, is carried out at a pH value of between 2 and 6 so that the carboxylic acid is extracted in situ to the organic solvent.
    Type: Application
    Filed: September 29, 2003
    Publication date: March 18, 2004
    Inventors: Thomas van der Does, Rienk Henrik Kuipers, Marjon Brigitte Diender, Jeroen Leonardus den Hollander, Adrianus Johannes Jozef Straathof, Lucas Antonius Maria van der Wielen, Joseph Johannes Heijnen
  • Publication number: 20030119086
    Abstract: The present invention is directed to novel polypeptides and to nucleic acid molecules encoding those polypeptides. Also provided herein are vectors and host cells comprising those nucleic acid sequences, chimeric polypeptide molecules comprising the polypeptides of the present invention fused to heterologous polypeptide sequences, antibodies which bind to the polypeptides of the present invention and to methods for producing the polypeptides of the present invention.
    Type: Application
    Filed: September 17, 2002
    Publication date: June 26, 2003
    Applicant: Genentech, Inc.
    Inventors: Kevin P. Baker, Dan L. Eaton, Ellen Filvaroff, Audrey Goddard, J. Christopher Grimaldi, Austin L. Gurney, Victoria Smith, Jean Philippe Stephan, Colin K. Watanabe, William I. Wood, Zemin Zhang, Sherman Fong
  • Patent number: 6503727
    Abstract: 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: Grant
    Filed: June 5, 1998
    Date of Patent: January 7, 2003
    Assignee: Gist-Brocades, B.V.
    Inventors: Wilhelmus H. J. Boesten, Wilhelmus J. J. Van Den Tweel, Rocus M. Dekkers
  • Patent number: 6391591
    Abstract: Novel microorganisms, which can be obtained by the following selection method: (a) microorganisms which grow using N-acetylglucosamine as the sole carbon source are cultivated in a customary manner, (b) from the resulting culture, these microorganisms are then selected which are stable and have the property to metabolize N-acetylglucosamine rapidly in the presence of N-Acetylmannosamine. Furthermore, a novel process for preparing NAM starting from a mixture of NAM and NAG.
    Type: Grant
    Filed: July 25, 2000
    Date of Patent: May 21, 2002
    Assignee: Lonzo Ltd.
    Inventors: Michael Petersen, Klaus Heinzmann
  • Patent number: 6383772
    Abstract: A first compound is converted to a second compound enzymatically in a solvent mixture containing water and a fluorinated, non-chlorinated alkane, alkene, or alkyne having up to 4 carbon atoms. Lactams, for example 6-aminopenicillanic acid (6-APA), may be prepared by enzymatic conversion of a first compound, for example penicillin-G, in a solvent mixture comprising water and a non-aqueous organic solvent, for example 1,1,1, 2-tetrafluoroethane. The 6-APA can be caused to precipitate, isolated by filtration and optionally derivatized to produce a desired compound. A by-product of the enzymatic conversion, for example phenylacetic acid, can be isolated by solvent extraction, suitably using a solvent which also comprises 1, 1, 1, 2-tetrafluoroethane.
    Type: Grant
    Filed: March 2, 2000
    Date of Patent: May 7, 2002
    Assignee: Advanced Phytonic Limited
    Inventor: Mazin Nicola
  • Patent number: 6379922
    Abstract: An enzyme membrane reactor is designed to enhance the production efficiency of foods, pharmaceutical products, and other bioproducts. The reactor is formed of a cap and a container in which a plurality of the biocatalyst-immobilized sheets are located at an interval. The reactor works in such a way that a liquid reaction mixture is introduced into the container via an inlet of the container, thereby resulting in the synthesis of a bioproduct mixture which is collected via an outlet of the reactor. The immobilized biocatalyst is prepared by entrapping a biocatalyst with a gluten matrix. The immobilized biocatalyst is deposited on supporting meshes contained by a plurality of frames that are inserted in a plurality of pairs of grooves contained by two opposite side walls of the container. Deactivated biocatalyst-immobilized sheets are replaceable and recyclable.
    Type: Grant
    Filed: September 20, 2000
    Date of Patent: April 30, 2002
    Assignee: National Science Council
    Inventor: Wen-Chien Lee
  • Patent number: 6359200
    Abstract: According to the invention, there is provided an inbred corn plant, designated 8M116. This invention thus relates to the plants and seeds of inbred corn plant 8M116 and to methods for producing a corn plant produced by crossing the inbred plant 8M116 with itself or with another corn plant. This invention further relates to hybrid corn seeds and plants produced by crossing the inbred plant 8M116 with another corn plant and to crosses with related species. This invention further relates to the inbred and hybrid genetic complements of inbred corn plant 8M116, and also relates to the RFLP and genetic isozyme typing profiles of inbred corn plant 8M116.
    Type: Grant
    Filed: January 13, 1994
    Date of Patent: March 19, 2002
    Assignee: Dekalb Genetics Corp.
    Inventor: Gary E. Day
  • Patent number: 6180360
    Abstract: 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: Grant
    Filed: June 15, 1999
    Date of Patent: January 30, 2001
    Assignee: Gist-Brocades
    Inventors: Svend Kaasgaard, Klaus Kristiansen, Henrik Mølgaard
  • Patent number: 6110699
    Abstract: Alternative process for obtaining 6-aminopenicillanic acid. The process comprises replacing the stages of extraction with organic solvents and isolation and separation of the intermediate penicillin salt as a solid by a process of ultrafiltration of the culture broth in at least 2 successive stages. The first stage has a cut-off for molecular weights of 20,000 Dalton and the second, 2000 Dalton. Subsequent to the enzyme conversion stage the products from that stage are subjected to a series of anionic exchange chromatography steps.
    Type: Grant
    Filed: February 25, 1998
    Date of Patent: August 29, 2000
    Assignee: Antibioticos, S.A.
    Inventors: Manuel Oliver Ruiz, Nieves Fraile Yecora, Emiliano Gonzalez De Prado, Alejandro Vitaller Alba, Francisco Salto Maldonado
  • Patent number: 6033823
    Abstract: New mutant .beta.-lactam Penicillin G acylases are provided, exhibiting altered substrate specificities. These Penicillin G acylases are obtained by expression of a gene encoding said Penicillin G acylase and having an amino acid sequence which differs at least in one amino acid from the wild-type Penicillin G acylase.
    Type: Grant
    Filed: April 5, 1999
    Date of Patent: March 7, 2000
    Inventors: Jan M. Van Der Laan, Adriana M. Riemens, Wilhelmus J. Quax
  • Patent number: 5902577
    Abstract: The invention relates to the field of biology and, in particular, to the field of cellular biology. The invention concerns a novel glucose-sensitive cell line designated .beta. cell line (INS-I) expressing glucokinase and the glucose carrier Glut 2 at levels comparable with those of normal .beta. cells but which is, in addition, incapable of IGF-II expression-dependent proliferation because of genetic manipulation. The invention also concerns a method for the production of said novel cell line, its aggregation in the form of a pseudoislet, its immobilization in a biocompatible hydrogel and its hardening by means of a hardening solution. Application in insulin-secreting .beta.-cell transplants.
    Type: Grant
    Filed: June 4, 1996
    Date of Patent: May 11, 1999
    Assignee: Merck Patent Gesellsschaft mit beschrankter Haftung
    Inventors: Maryam Asfari, Paul Czernichow
  • Patent number: 5891703
    Abstract: New mutant .beta.-lactam Penicillin G acylases are provided, exhibiting altered substrate specificities. These Penicillin G acylases are obtained by expression of a gene encoding for said Penicillin G acylase and having an amino acid sequence which differs at least in one amino acid from the wild-type Penicillin G acylase.
    Type: Grant
    Filed: April 23, 1997
    Date of Patent: April 6, 1999
    Assignee: Gist-Hrocades
    Inventors: Jan M. Van Der Laan, Adriana M. Riemens, Wilhelmus J. Quax
  • Patent number: 5780260
    Abstract: 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: Grant
    Filed: May 30, 1996
    Date of Patent: July 14, 1998
    Assignee: Boehringer Mannheim GmbH
    Inventors: Frank Wedekind, Adelheid Daser, Wilhelm Tischer
  • Patent number: 5521068
    Abstract: The invention relates to an improved process for converting 6-acylaminopenicillanic acid (6-AAPA) to 6-aminopenicillanic acid (6-APA). The process employs a solution or suspension of penicillin acylase from which the product is separated after reaction by ultrafiltration through a particular class of polymer membranes. The process of the invention may also be applied to the production of 7-aminodesacetoxycephalosporanic acid (7-ADCA) and can be incorporated into an improved, streamlined process for obtaining 6-APA from fermentation broths.
    Type: Grant
    Filed: February 9, 1995
    Date of Patent: May 28, 1996
    Assignee: Sepracor, Inc.
    Inventor: Jorge L. Lopez
  • Patent number: 5500352
    Abstract: The invention relates to an improved process for converting 6-acylaminopenicillanic acid (6-AAPA) to 6-aminopenicillanic acid (6-APA). The process employs a solution or suspension of penicillin acylase from which the product is separated after reaction by ultrafiltration through a particular class of polymer membranes. The process of the invention may also be applied to the production of 7-aminodesacetoxycephalosporanic acid (7-ADCA) and can be incorporated into an improved, streamlined process for obtaining 6-APA from fermentation broths.
    Type: Grant
    Filed: March 24, 1993
    Date of Patent: March 19, 1996
    Assignee: Sepracor, Inc.
    Inventor: Jorge L. Lopez
  • Patent number: 5457032
    Abstract: New mutant .beta.-lactam acylases are provided exhibiting altered substrate specificities. These .beta.-lactam acylases are obtained by expression of a gene encoding said .beta.-lactam acylase and having an amino acid sequence which differs at least in one amino acid from the wild-type .beta.-lactam acylase.
    Type: Grant
    Filed: May 9, 1991
    Date of Patent: October 10, 1995
    Assignee: Gist-brocades NV
    Inventors: Wilhelmus J. Quax, Onno Misset, Jan M. Van Der Laan, Herman B. M. Lenting
  • Patent number: 5356781
    Abstract: 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: Grant
    Filed: June 26, 1991
    Date of Patent: October 18, 1994
    Assignee: Bioscience International, Inc.
    Inventors: John Hermon-Taylor, Brian M. Austen
  • Patent number: 5268271
    Abstract: Synthesis of semi-synthetic monobactamic or .beta.-Lactamic antibiotics by using derivatives stabilized by various methods of penicillin G acylase from various microbial sources according to a thermodynamically controlled strategy in monophase water/cosolvent organic apolar systems, wherein the concentration of the cosolvent varies between 30% and 90%, the temperature between -10.degree. C. and 50.degree. C., the pH between 4.5 and 8.5, with concentrations of the antibiotic nucleus between 0.5 an 875 mM and acyl donor between 0.2 mM and 1M, with a relationship antibiotic ring/activated or free acyl donor, using a buffer between 0 and 1M. Application to the pharmaceutical industry.
    Type: Grant
    Filed: August 2, 1991
    Date of Patent: December 7, 1993
    Assignee: Cosejo Superior de Invetigaciones Certificas
    Inventors: Jose M. Guisan Seijas, Roberto Fernandez Lafuente, Gregorio Alvaro Campos, Rosa M. Blanco Martin, Cristina Molina Rosell
  • Patent number: 5215891
    Abstract: A process for preparing a compound of formula I: ##STR1## wherein R.sub.1 represents a hydroxy protecting group and R.sub.2 represents a carboxy protecting group, which comprises:hydrolyzing a compound of formula II ##STR2## wherein R.sub.1 and R.sub.2 are as defined above and R represents an alkyl, alkenyl or phenylalkyl group having from 1 to 18 carbon atoms, in the presence of an enzyme capable of selectively hydrolyzing the ester group of the 2-substituent thereof.
    Type: Grant
    Filed: March 9, 1992
    Date of Patent: June 1, 1993
    Assignee: Farmitalia Carlo Erba
    Inventors: Maria Altamura, Pietro Cesti, Franco Francalanci, Marcello Marchi, Marco Foa', Stefano Cambiaghi, Franco Dallatomasina
  • Patent number: 5079146
    Abstract: The present invention relates to a new method of protection of the carboxy group in the chemistry of the compounds of .beta.-lactam type. According to such a method, the carboxy group is protected by being transformed into its corresponding phenyl-acetoxy-methyl ester, which is then removed by an enzymatic route by means of penicillinacylase.In particular, if the .beta.-lactam compound also bears a phenyl-acetamidic substitutent, this latter is simultaneously hydrolysed during the same step of removal of the carboxy function protecting group.
    Type: Grant
    Filed: April 4, 1989
    Date of Patent: January 7, 1992
    Assignee: Sclavo S.p.A.
    Inventors: Claudio Fuganti, Eva Baldaro, Daniela Faiardi, Ameriga Lazzarini
  • Patent number: 4371612
    Abstract: Biological material such as enzymes is immobilized by adsorption or covalent bonding to a micro-porous water-insoluble acrylonitrile polymer containing from 20 .mu.M to 1000 .mu.M of amino groups per gram of the polymer. Covalent bonding may be carried out with a crosslinking or condensing agent. The amino groups may be introduced into the polymer by reduction of nitrile groups with lithium aluminum hydride in an inert non-solvent.
    Type: Grant
    Filed: December 1, 1980
    Date of Patent: February 1, 1983
    Assignee: Toyo Jozo Company, Ltd.
    Inventors: Kunio Matsumoto, Rokuro Izumi, Hideji Seijo, Hiroyuki Mizuguchi
  • Patent number: 4370414
    Abstract: A process for producing 6-aminopenicillanic acid and 6-aminopenicillanic acid S-oxide by means of enzymes produced by microbes belonging to Arthrobacter genus, especially Arthrobacter cremorum and Arthrobacter flagellum.
    Type: Grant
    Filed: October 6, 1980
    Date of Patent: January 25, 1983
    Assignee: Shionogi & Co., Ltd.
    Inventors: Takashi Mitsugi, Ryonosuke Muneyuki, Yoshiharu Wakisaka, Kenzo Koizumi, Eiji Kondo
  • Patent number: 4267273
    Abstract: An enzyme preparation is prepared having terminal non-polar groups incorporated therein so that the enzyme preparation has affinity for a water-immiscible liquid. The enzyme preparation can be separated from an aqueous reaction mixture by contacting the mixture with the water-immiscible liquid, permitting the enzyme preparation to become associated with the water-immiscible liquid and separating the water-immiscible liquid containing the associated enzyme from the reaction mixture.
    Type: Grant
    Filed: April 12, 1979
    Date of Patent: May 12, 1981
    Assignee: Beecham Group Limited
    Inventor: Richard A. G. Smith
  • Patent number: 4247643
    Abstract: Stabilized carrier-bound protein is prepared by reacting a protein in aqueous solution with a mercapto group free, water insoluble carrier which contains binding groups which are reactive with the said protein and reacting the resultant protein-containing mercapto group-free carrier with hydrogen sulfide or with a compound having a molecular weight of less than 5000, and which contains at least two mercapto groups, or at least one mercapto group and at least one hydroxy- group or primary or secondary amino group.
    Type: Grant
    Filed: July 13, 1978
    Date of Patent: January 27, 1981
    Assignee: Rohm GmbH Chemische Fabrik
    Inventors: Dieter Kramer, Klaus Sauber
  • Patent number: 4246346
    Abstract: A method for activating immobilized living microorganisms applied to transformations of steroids, antibiotics and other compounds characterized by the addition of peptone, glucose or a mixture of peptone and glucose to the reaction mixture.
    Type: Grant
    Filed: September 5, 1978
    Date of Patent: January 20, 1981
    Assignee: Aktiebolaget Fermenta
    Inventors: Per-Olof Larsson, Klaus H. Mosbach, Sten A. Ohlson