By Acylation Of The Substituent In The 7-position Patents (Class 435/50)
  • Patent number: 8252599
    Abstract: Sample processing units useful for mixing and purifying materials, such as fluidic materials are provided. A sample processing unit typically includes a container configured to contain a sample comprising magnetically responsive particles, and one or more magnets that are in substantially fixed positions relative to the container. A sample processing unit also generally includes a conveyance mechanism configured to convey the container to and from a position that is within magnetic communication with the magnet, e.g., such that magnetically responsive particles with captured analytes can be retained within the container when other materials are added to and/or removed from the container. Further, a sample processing unit also typically includes a rotational mechanism that is configured to rotate the container, e.g., to effect mixing of sample materials disposed within the container. Related carrier mechanisms, sample processing stations, systems, and methods are also provided.
    Type: Grant
    Filed: August 30, 2011
    Date of Patent: August 28, 2012
    Assignee: Ibis Biosciences, Inc.
    Inventors: Steven A. Hofstadler, Jared J. Drader, Jose R. Gutierrez, Paul J. Gleason, Rex O. Bare, Robert D. Miller, Jeffrey C. Smith
  • Patent number: 8071330
    Abstract: The present invention relates to a process for the synthesis of cefaclor, which process comprises reacting 7-amino-3-chloro cephalosporanic acid (7-ACCA) with D-phenylglycine in activated form (PGa) in the presence of an enzyme in a reaction mixture to form cefaclor, wherein at least part of 7-ACCA and/or PGa are added to the reaction mixture during the course of the reaction. The invention also relates to an aqueous mixture comprising an amount of cefaclor of >10 (w/w) %, an amount of 7-amino-3-chloro cephalosporanic acid of <2 (w/w) %, and an amount of D-phenyl glycine of <2 (w/w) % and a process for the recovery of cefaclor from this aqueous mixture. The invention also relates to cefaclor in crystal form having an absorbance at 400 nm (A400) of less than 0.250.
    Type: Grant
    Filed: December 23, 2005
    Date of Patent: December 6, 2011
    Assignee: DSM IP Assets B.V.
    Inventors: Harold Monro Moody, Theodorus Johannes Godfried Maria Van Dooren
  • Patent number: 7588913
    Abstract: The present invention describes a process for preparing cephradine, said process comprising reacting 7-aminodesacetoxy cephalosporanic acid (7-ADCA) with D-dihydrophenylglycine in activated form (DHa) in the presence of an enzyme in a reaction mixture to form cephradine, resulting in a conversion of 7-ADCA into cephradine of at least 70%, wherein the concentration D-dihydrophenylglycine (DH) in the reaction mixture is below 2 wt.%, wherein the conversion of 7-ADCA into cephradine & equals; (nCEF/n7-ADCA)*100%, wherein nCEF=quantity of cephradine formed (in mole); and n7-ADCA=total quantity of 7-ADCA added to reaction mixture (in mole).
    Type: Grant
    Filed: July 1, 2004
    Date of Patent: September 15, 2009
    Assignee: DSM IP Assets B.V.
    Inventors: Dennis Heemskerk, Anja Gerarda Margaretha Hogenboom, Carlos Enrique Lenhardt, Harold Monro Moody, Theodorus Johannes Godfried Maria Van Dooren
  • Patent number: 7241630
    Abstract: A method of determining the number of magnetic particles within a sample using a tuned circuit having a capacitor and a coil. The method comprises: a. determining the difference in the resonant frequency of the tuned circuit when the sample is exposed to a magnetic field generated by the coil and when the sample is not exposed to the magnetic field generated by the coil; and b. using the difference in the resonant frequency to determine the number of magnetic particles within the sample.
    Type: Grant
    Filed: March 26, 2001
    Date of Patent: July 10, 2007
    Assignee: Randox Laboratories, Ltd.
    Inventors: Peter Hawkins, Richard William Luxton
  • Patent number: 6942990
    Abstract: The invention provides a glutaryl 7-ACA amidase from Pseudomonas diminuta strain BS-203, which catalyzes the hydrolysis of 7-?-(4-carboxybutanamido)-cephalosporanic acid to 7-aminocephalosporanic acid and glutaric acid. The invention also provides nucleic acid sequences, vectors, and host cells useful in the production of this amidase. The glutaryl 7-ACA amidase can be used for the preparation of 7-aminocephalosporanic acid.
    Type: Grant
    Filed: January 17, 2003
    Date of Patent: September 13, 2005
    Assignee: Bristol Myers Squibb Company
    Inventors: Ross Binder, Joanne L. Brown, Thomas J. Franceschini, William V. Burnett, Michael Politino, Suo Win Liu, Sean M. Tonzi
  • Patent number: 6518039
    Abstract: The present invention discloses a process for the production of N-deacylated cephalosporin compounds via the fermentative production of their 7-acylated counterparts.
    Type: Grant
    Filed: May 17, 1999
    Date of Patent: February 11, 2003
    Assignee: DSM N.V.
    Inventors: Maarten Nieboer, Erik De Vroom, Johannis Lugtenburg, Dirk Schipper, Adrianus Wilhelmus Hermanus Vollebregt, Roelof Ary Lans Bovenberg
  • 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
  • Publication number: 20020037547
    Abstract: The present invention discloses a process for the production of N-deacylated cephalosporin compounds via the fermentative production of their 7-acylated counterparts.
    Type: Application
    Filed: May 17, 1999
    Publication date: March 28, 2002
    Inventors: MAARTEN NIEBOER, ERIK DE VROOM, JOHANNIS LUGTENBURG, DIRK SCHIPPER, ADRIANUS WILHELMUS H VOLLEBREGT, ROELOF ARY LANS BOVENBERG
  • Patent number: 6319684
    Abstract: 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: Grant
    Filed: August 26, 1999
    Date of Patent: November 20, 2001
    Assignee: DMS N.V.
    Inventors: John Krijgsman, Jan Willem Hubert Smeets, Henriƫtte Elisabeth Anna De Braal, Erik De Vroom, Herman Pieter Fasel
  • Patent number: 6287799
    Abstract: Process for the preparation of a &bgr;-lactam antibiotic in which a &bgr;-lactam nucleus is subjected to an enzymatic acylation reaction with the aid of an acylation agent at a molar ratio of acylation agent/&bgr;-lactam nucleus of less than 2.5, with the acylation agent and/or the &bgr;-lactam nucleus being supersaturated in the reaction mixture during at least part of the acylation reaction. In the process, a concentrated slurry or solution, for instance, of the &bgr;-lactam nucleus and/or the acylation agent with a different pH or a higher temperature than the pH or temperature at which the acylation reaction is carried out is added to the reaction mixture during the acylation reaction. Both the &bgr;-lactam nucleus and the acylation agent may be supersaturated in the reaction mixture.
    Type: Grant
    Filed: April 18, 2000
    Date of Patent: September 11, 2001
    Assignee: DSM N.V.
    Inventors: Theodorus Johannes Godfried Marie Van Dooren, Johanna Christina Maria Smeets, Harold Monro Moody
  • Patent number: 6218138
    Abstract: Beta-lactam antibiotics are synthesized by reacting an amino-beta-lactam component with a corresponding amino-group-containing acylating side-chain component in the presence of penicillin amidase from E. coli covalently immobilized on support particles. The resulting beta-lactam antibiotic product is solubilized by adding an acid such as sulfuric acid to lower the pH to 1.0 at a temperature in the range of 0° C. to +5° C. The immobilized penicillin amidase is substantially inactivated by the acid. After separating the beta-lactam antibiotic product, the immobilized penicillin amidase is substantially reactivated for reuse in antibiotic synthesis by treatment with a buffer having about a neutral pH. Antibiotics that can be produced include ampicillin, amoxicillin, cephalexin, cefaclor and cefadroxil.
    Type: Grant
    Filed: May 26, 1999
    Date of Patent: April 17, 2001
    Assignee: Unifar Kimya Sanayi ve Ticaret A.S.
    Inventors: Ferhat Ilhan, Dieter Kraemer
  • Patent number: 6060268
    Abstract: Penicillin G acylase is immobilized by covalent bonding to a crosslinked mixture of a gelled gelling agent such as gelatin and a polymer containing free amino groups such as alginate amine, chitosan or polyethylene imine. The immobilized penicillin G acylase provides a higher synthesis/hydrolysis ratio as compared to immobilizing with other carriers when producing .beta.-lactam derivatives by a condensing reaction of an amino .beta.-lactam with an acylating agent. The acylating agent may be a derivative of D-phenylglycine, a derivative of D-p-hydroxyphenylglycine or a derivative of D-2,5-dihydro-phenylglycine. Examples of .beta.-lactam derivatives that can be produced are amoxycillin, ampicillin, cephaclor, cephadroxil, cephprozil, cephalexin and cephradine.
    Type: Grant
    Filed: January 15, 1998
    Date of Patent: May 9, 2000
    Assignee: Gist-Brocades B.V.
    Inventor: Erik De Vroom
  • Patent number: 5874571
    Abstract: The disclosed process is for the recovery of cephalexin from a mixture containing cephalexin and 7-aminodesacetoxy cephalosporanic acid (7-ADCA), wherein a mixture of cephalexin and 7-ADCA, with a pH higher than 7, which apart from any solid cephalexin being present is homogeneous at a pH between 7 and 8.5, is subjected to a pH modification until a pH lower than 7.8 is reached, and the solid substance is recovered. The disclosed process is particularly suited for application to a reaction mixture obtained after the enzymatic acylation reaction of 7-ADCA with a phenylglycine derivative as an acylation agent. Pure cephalexin can thus be recovered in a simple manner.
    Type: Grant
    Filed: July 31, 1997
    Date of Patent: February 23, 1999
    Assignee: Chemferm V.O.F.
    Inventors: Wilhelmus H. J. Boesten, Eric C. Roos, Wilhelmus J. J. van den Tweel
  • 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: 5753458
    Abstract: 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: Grant
    Filed: February 7, 1996
    Date of Patent: May 19, 1998
    Assignee: Gist-Brocades B.V.
    Inventors: Kim Clausen, Annette Nielsen, Niels Petersen, Alexander Nikolov
  • Patent number: 5525483
    Abstract: .beta.-Lactam derivatives are synthesized by an enzymatic reaction of the parent amino .beta.-lactam with the corresponding acylating agent, the concentration of the acylating agent plus the concentration of .beta.-lactam derivative in the reaction mixture being above about 400 mM.
    Type: Grant
    Filed: January 18, 1994
    Date of Patent: June 11, 1996
    Assignee: Gist Brocades B.V.
    Inventors: Svend G. Kaasgaard, Ulla Veitland
  • Patent number: 5512454
    Abstract: 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: Grant
    Filed: February 3, 1994
    Date of Patent: April 30, 1996
    Assignee: Bristol-Myers Squibb Company
    Inventors: John J. Usher, Guna Romancik, Michael Politino, David A. Lowe
  • Patent number: 5470717
    Abstract: The present invention relates to an improved method for the preparation of certain .beta.-lactam antibiotics by enzymatic acylation or by deprotection of a protected intermediate.
    Type: Grant
    Filed: May 12, 1994
    Date of Patent: November 28, 1995
    Assignee: Gist-Brocades N.V.
    Inventor: Kim Clausen
  • Patent number: 5296358
    Abstract: The enzymatic preparation of cephalosporanic derivatives, or their salts, ving the formula: ##STR1## wherein R is --CO--COOH or --COOH, R.sub.1 is H, OH, or --O--CO--R" and R" is an alkyl group with 1 to 4 carbon atoms, is carried out by the oxidative deamination of compounds, or their salts, having the formula: ##STR2## with an oxidase D-Aminoacid enzyme derived from Rhodotorula glutinis NCIMB 40412. The enzyme can be in a free or immobilized form.
    Type: Grant
    Filed: June 3, 1992
    Date of Patent: March 22, 1994
    Assignee: Ministero Dell'Universita' e Della Ricerca Scientifica e Tecnologica
    Inventors: Ezio A. Battistel, Pietro Cesti, Giuliana Franzosi, Vilhelmus van der Goes, Silvana Bonicelli, Mirella Pilone
  • 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: 4945159
    Abstract: A method for the formation of intramolecular amide bonds by the action of cyanogen, under mild reaction conditions, in the preparation of cyclic amides, including lactams, in biologically active compounds. A compound containing at least one carboxylic acid group and at least one primary or secondary amino group is reacted with cyanogen to form an intramolecular amide bond. The method has utility in the synthesis of B-lactam antibiotics, such as penicillins, cephalosporins, and their derivatives, in enzyme modification, in cyclization of peptides, and in covalent cross-linking of proteins.
    Type: Grant
    Filed: December 2, 1986
    Date of Patent: July 31, 1990
    Assignee: University of Cincinnati
    Inventor: Richard A. Day
  • Patent number: 4340672
    Abstract: Penicillins and cephalosporins can be synthesized by the action of an acylase on a penicillin or cephalosporin nucleus amine as substrate and an ester (I) of the following formula as the acyl source: ##STR1## (wherein RCO is an acyl group in penicillin or cephalosporin side chains;X is a hydrogen atom, lower alkyl group or hydroxy-lower alkyl group;Y is a hydrogen atom or a lower alkyl group; and n is a positive integer).The novel acyl source (I) is also disclosed.
    Type: Grant
    Filed: September 19, 1980
    Date of Patent: July 20, 1982
    Assignee: Shionogi & Co., Ltd.
    Inventors: Eiji Kondo, Takashi Mitsugi, Tamio Fujiwara, Ryonosuke Muneyuki
  • Patent number: 4335211
    Abstract: Disclosed are optically active acylated cephalosporin analogs which are useful as antibacterial agents and methods for preparing such compounds.
    Type: Grant
    Filed: November 13, 1980
    Date of Patent: June 15, 1982
    Assignee: Kyowa Hakko Kogyo Co., Ltd.
    Inventors: Yukio Hashimoto, Seigo Takasawa, Tadashi Hirata, Ikuo Matsukuma, Shigeo Yoshiie