Preparing Compound Having A 1-thia-4-aza-bicyclo (3.2.0) Heptane Ring System (e.g., Penicillin, Etc.) Patents (Class 435/43)
  • 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: 5013452
    Abstract: A method for resolving emulsions produced in preparation of pharmaceuticals by fermentation and in other such bioprocesses is disclosed. The method comprises adding an effective amount of a demulsifier to an emulsion containing fermentation product that includes a pharmaceutical which is desired to be extracted from the emulsion.
    Type: Grant
    Filed: December 4, 1989
    Date of Patent: May 7, 1991
    Assignee: Petrolite Corporation
    Inventors: Thomas J. Bellos, Richard D. Keating
  • Patent number: 5008188
    Abstract: Process for producing S-adenosyl-L-homocysteine, which comprises reacting adenosine with homocysteine by contacting them in an aqueous medium in the presence of cells or treated cells of a microorganism of a specified genus having the ability to synthesize S-adenosyl-L-homocysteine from adenosine and homocysteine, and collecting the S-adenosyl-L-homocysteine synthesized.
    Type: Grant
    Filed: November 4, 1987
    Date of Patent: April 16, 1991
    Assignee: Nippon Zeon Co., Ltd.
    Inventors: Hideaki Yamada, Yoshiki Tani, Sakayu Shimizu, Shozo Shiozaki
  • Patent number: 4980284
    Abstract: A substantial elevation of the space-time yield is achieved in the preparation of D-.alpha.-amino acids by means of the biotransformation of hydantoins which are monosubstituted in the 5-position in an aqueous medium in the presence of cells of the microorganism Agrobacterium radiobacter if the biotransformation is carried out under a elevated pressure at the start of the reaction. A further improvement results if this elevated pressure is maintained for a period of at least 16 hours, then removed and the biotransformation continued at atmospheric pressure.
    Type: Grant
    Filed: May 25, 1990
    Date of Patent: December 25, 1990
    Assignee: Degussa AG
    Inventors: Kyriakos Makryaleas, Karlheinz Drauz
  • Patent number: 4980282
    Abstract: A process for the treatment of corn steepwater. The steepwater is incubated for a sufficient time to develop biomass before corn steepwater is fed continuously to the developed biomass at a rate such that the residence time of the steepwater in contact with the biomass is in excess of 4 hours.
    Type: Grant
    Filed: November 19, 1987
    Date of Patent: December 25, 1990
    Assignee: CPC International Inc.
    Inventors: Jean-Claude de Troostembergh, Francoise Oudeene
  • Patent number: 4865973
    Abstract: A process for producing a variety of chemical products, e.g., ethanol, by fermentation in which the product is removed from the fermentation medium as it is formed by liquid-liquid extraction using an extractant for the product which is immiscible with water. The extractant employed is chosen from the following groups: (A) double bond unsaturated aliphatic alcohols having 12 or more carbon atoms; (B) saturated branched chain aliphatic alcohols having 14 or more carbon atoms or mixtures thereof; (C) double bond unsaturated aliphatic acids having 12 or more carbon atoms; (D) aliphatic and aromatic mono-, di- or tri-esters having 12 or more carbon atoms, other than dibutyl phthalate; (E) aliphatic noncyclic ketones and aliphatic aldehydes having 12 or more carbon atoms; and (F) mixtures of extractants from groups (A) to (E) above or mixtures of at least one of the above extractants and at least one other extractant.
    Type: Grant
    Filed: August 13, 1986
    Date of Patent: September 12, 1989
    Assignee: Queen's University at Kingston
    Inventors: Finn Kollerup, Andrew J. Daugulis
  • Patent number: 4847200
    Abstract: A process for producing unnatural penicillins and cephalosporin derivatives thereof in which peptide analogs of ACV in which the L-.alpha.-aminodipyl moiety is replaced by L-S-carboxymethyl cysteine or other obvious substituents, are reacted with cyclase, epimerase, ring expansion and hydroxylase enzymes isolated from a cell free extract of a prokaryotic organism such as S. clavuligerus. The product depends upon the presence or absence of co-factors such as ferrous ion, .alpha.-ketoglutarate, and ascorbate. In an alternative embodiment, a penicillin analog having the formula: ##STR1## may be reduced with L-cysteine to produce an analog of isopenicillin N which may be reacted with the enzyme reagent to produce the desired penicillin or cephalosporin.
    Type: Grant
    Filed: September 5, 1986
    Date of Patent: July 11, 1989
    Assignee: Queen's University at Kingston
    Inventors: Saul Wolfe, Donald Westlake, Susan Jensen
  • Patent number: 4769325
    Abstract: 2-(Allenyl)penicillins antibiotics and intermediates thereto are disclosed. A process for making the 2-(allenyl)penicillins and the starting materials for the process are also disclosed.
    Type: Grant
    Filed: July 28, 1986
    Date of Patent: September 6, 1988
    Inventors: Jack E. Baldwin, Amit Basak
  • Patent number: 4732851
    Abstract: A composition comprising immobilized cells obtained by applying a dispersion of cells and curable prepolymer material selected from the group consisting of polyazetidine prepolymers, carboxymethyl cellulose, polyurethane hydrogel prepolymers and polymethylene isocyanates. as a coating to a solid inert carrier and curing the prepolymer on the carrier at a temperature below the temperature at which enzyme activity of the cells is significantly reduced. The composition may be used to produce various materials such as L-aspartic acid, L-alanine, 6-Aminopenicillanic acid, high fructose corn syrup, prednisolone or phenylalanine.
    Type: Grant
    Filed: February 10, 1983
    Date of Patent: March 22, 1988
    Assignee: Purification Engineering, Inc.
    Inventors: Louis L. Wood, Gary J. Calton
  • Patent number: 4722924
    Abstract: A compound of formula I or a physiologically acceptable salt thereof ##STR1## wherein X represents sulphur or methylene, R.sub.1 represents hydrogen, amino or an acylated or carbamylated amino group, R.sub.2 represents hydrogen or an alkyl group and R.sub.3 represents an alkoxy group.
    Type: Grant
    Filed: August 22, 1985
    Date of Patent: February 2, 1988
    Assignee: National Research Development Corporation
    Inventor: Jack E. Baldwin
  • Patent number: 4710457
    Abstract: This invention concerns a new monoclonal antibody (mAb) 4C, recognizing a specific antigen, Leu 200, found in human hematopoietic tissues. The monoclonal antibody precipitates a series of glycoproteins (Leu 200) with a molecular weight range of about 190,000 to 230,000 from both T- and B-cell lines. The series of glycoproteins resolves into four discrete glycoprotein bands, the distribution of which varies according to the cell lines. Bands 3 and 4 predominate in a majority of T-cells whereas band 2 predominates in B cells. Thus, a Leu 200 antigen subset distribution is possible with mAb 4C. Bands 1, 2, 3, 4 have apparent molecular weights of 230K, 215K, 205K, and 190K respectively, with differences in their carbohydrate moieties. mAb 4C is a IgG sub two a, kappa immunoglobulin. 4C has potential use in leukemia, hematopoietic cell differentiation and transplantation diagnoses and therapy.
    Type: Grant
    Filed: June 29, 1983
    Date of Patent: December 1, 1987
    Assignee: Sloan-Kettering Institute for Cancer Research
    Inventors: Bo Dupont, Yasuo Morishima, Nancy Collins, Shun-ichiro Ogata, Kenneth O. Lloyd
  • Patent number: 4709015
    Abstract: Hybrid cell line for production of monoclonal antibody to an antigen found on normal human suppressor T cells. The hybrid is formed by fusing splenocytes from immunized CAF.sub.1 mice with P3X63Ag8Ul myeloma cells. Diagnostic and therapeutic uses of the monoclonal antibody are also disclosed.
    Type: Grant
    Filed: August 9, 1984
    Date of Patent: November 24, 1987
    Assignee: Ortho Pharmaceutical Corporation
    Inventors: Patrick C. Kung, Gideon Goldstein
  • Patent number: 4693977
    Abstract: Enzymes extracted from a prokaryotic .beta.-lactam producing microorganism are immobilized on a support for producing desacetoxycephalosporin and analogs thereof from L-.alpha.-aminoadipyl-L-cysteinyl-D-valine and analogs thereof. The enzymes are an epimerase, a cyclase and a ring expansion enzyme extracted preferably from S. clavuligerus, S. cattleya or S. lipmanii. The support is preferably a diethylaminoethyl ion exchange resin.
    Type: Grant
    Filed: January 23, 1986
    Date of Patent: September 15, 1987
    Assignee: Queen's University at Kingston
    Inventors: Saul Wolfe, Donald Westlake, Susan Jensen
  • Patent number: 4666835
    Abstract: 6.beta.-(L-.alpha.-Aminoadipoyl)-2.alpha.-vinyl-2.beta.-methylpenam-3-carbo xylic acid is provided in an enzymatic process converting .delta.-(L-.alpha.-aminoadipoyl)-L-cysteinyl-D-.gamma.,.delta.-didehydrois oleucine with isopenicillin N synthetase. The 2.alpha.-vinylpenam product is converted by known methods to the 6.beta.-amino-2.alpha.-vinyl-2.beta.-methylpenam-3-carboxylic acid nucleus and the latter is N-acylated to provide corresponding 6.beta.-acylaminopenams.
    Type: Grant
    Filed: April 29, 1986
    Date of Patent: May 19, 1987
    Inventor: Jack E. Baldwin
  • Patent number: 4661586
    Abstract: Monoclonal anti-idiotype antibodies against cell surface Ig of human B-cell tumors, labeled conjugates of such antibodies, immunotherapeutic compositions containing such antibodies, and a process for making such antibodies. The nodular lymphoma of a patient treated with a monoclonal anti-idiotpye antibody against the cell surface IgM of the patient's tumor went into complete remission.
    Type: Grant
    Filed: December 2, 1983
    Date of Patent: April 28, 1987
    Assignee: The Board of Trustees of the Leland Stanford Junior University
    Inventors: Ronald Levy, Jeanette Dilley, David G. Maloney, Richard A. Miller
  • Patent number: 4650755
    Abstract: Microbial cells are immobilized with a curable polyaziridine or polyfunctional aziridine prepolymer to obtain an insoluble, crosslinked polymer containing the cells. The microbial cells immobilized may be cells having L-aspartase or L-phenylalanine transaminase activity for the production of L-aspartic acid or L-phenylalanine. The polymer containing the cells may be formed as a coating on a solid inert carrier.
    Type: Grant
    Filed: August 14, 1984
    Date of Patent: March 17, 1987
    Assignee: Purification Engineering, Inc.
    Inventors: Louis L. Wood, Gary J. Calton
  • Patent number: 4564444
    Abstract: A system for controlling a process utilizing filamentous microorganisms is disclosed. The amount of the microorganisms in a medium for growing the filamentous microorganisms is measured, and the control factors associated with the growth of the microorganisms in the medium are controlled on the basis of the measurement of the amount of microorganisms. In the process of measuring the amount of microorganisms, an optical image of a specimen of the medium is formed and scanned two-dimensionally to produce a series of brightness signals corresponding to the brightness distribution of the optical image. The level of the brightness signal is used to determine the amount of the microorganisms contained in the medium.
    Type: Grant
    Filed: July 26, 1984
    Date of Patent: January 14, 1986
    Assignee: Hitachi, Ltd.
    Inventors: Masakatsu Hiraoka, Kazushi Tsumura, Kenji Baba, Shunsuke Nogita, Shunji Mori
  • Patent number: 4536476
    Abstract: Cyclase, epimerase and a ring expansion enzyme are isolated separately from a cell free extract of a prokaryotic beta-lactam producing organism to provide three separate and stable enzyme reagents for commercial production of cephalosporins from peptide precursors. Isolation is carried out by using ammonium sulfate, gel filtration and ion exchange chromatography. The enzymes may be immobilized on a suitable support and the production of cephalosporins may be carried out continuously.
    Type: Grant
    Filed: June 27, 1983
    Date of Patent: August 20, 1985
    Assignee: Queen's University at Kingston
    Inventors: Saul Wolfe, Donald Westlake, Susan Jensen
  • Patent number: 4510246
    Abstract: The enzymes, cyclase, epimerase and a ring expansion enzyme, are isolated separately from a cell-free extract of a prokaryotic beta-lactam producing organism. The isolated enzymes are used to produce unnatural cephalosporins from polypeptide precursors. Isolation is carried out by adding ammonium sulfate to 40% saturation to the cell-free extract to precipitate contaminating proteins, adding ammonium sulfate to 70% saturation to the resultant supernatant to precipitate the enzymes, suspending the precipitated enzymes in a buffer, separating epimerase from the suspension by gel filtration, and separating cyclase and the ring expansion enzyme from each other by ion exchange chromatography.
    Type: Grant
    Filed: August 23, 1982
    Date of Patent: April 9, 1985
    Assignee: Queen's University at Kingston
    Inventors: Saul Wolfe, Donald Westlake, Susan Jensen
  • Patent number: 4413056
    Abstract: A process for the preparation of a compound of formula (I): ##STR1## wherein R.sup.1 is hydrogen, hydroxy, mercapto radical, a substituted or unsubstituted methoxy, ethoxy, methyl, ethyl, methyl thio, or ethylthio radical, a carbamoyloxy, carbamoylthio, C.sub.1-6 alkanoyloxy, C.sub.1-6 alkanoylthio, cyano, carboxy or carbamoyl radical; andR.sup.2 represents an acyl group which comprises hydrolysis of a compound of formula (II): ##STR2## wherein R.sup.1 and R.sup.2 are as defined with respect to formula (I) hereinbefore and R.sup.3 represents benzyl or substituted benzyl; wherein the hydrolysis is catalyzed by a microbial serine proteinase.
    Type: Grant
    Filed: October 19, 1981
    Date of Patent: November 1, 1983
    Assignee: Beecham Group Limited
    Inventors: Ian R. Chester, Lawson W. Powell, David G. Roberts
  • Patent number: 4359528
    Abstract: The invention relates to a corn-steeping process. In this process the temperature of the steeping water decreases from silo to silo and the cycling ratio is comprised between 0.8 and 1.2 m.sup.3 per ton of commercial corn.The Corn-Steep obtained can be applied especially in the manufacture of penicillin.
    Type: Grant
    Filed: August 28, 1980
    Date of Patent: November 16, 1982
    Assignee: Roquette Freres
    Inventors: Francis Devos, Patrick Beuque, Michel Huchette
  • Patent number: 4347314
    Abstract: A process for the preparation of .alpha.-carboxy, 6, .alpha.-methoxy penicillin derivatives by the enzymatic hydrolysis of an esterified derivative.The process is for the preparation of a compound of formula (I): ##STR1## wherein R represents phenyl or 2- or 3-thienyl, which process comprises subjecting a compound of formula (IV): ##STR2## where R.sup.1 is an aryl radical, to the action of an enzyme selected from bromelain, papain, gelatase, trypsin, pancreatin or an esterase-producing strain of Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger or Saccharomyces sp.
    Type: Grant
    Filed: May 13, 1980
    Date of Patent: August 31, 1982
    Assignee: Beecham Group Limited
    Inventors: Martin Cole, Robert A. Edmondson
  • Patent number: 4346168
    Abstract: A process for the preparation of .alpha.-carboxy, 6, .alpha.-methoxy penicillin derivatives by the enzymatic hydrolysis of an esterified derivative.The process is for the preparation of a compound of formula (I): ##STR1## wherein R represents phenyl or 2- or 3-thienyl, which process comprises subjecting a compound of formula (IV): ##STR2## wherein R.sup.1 is an ester-forming radical, to the action of the enzyme .alpha.-chymotrypsin or an esterase-producing strain of Streptomyces sp.
    Type: Grant
    Filed: May 13, 1980
    Date of Patent: August 24, 1982
    Assignee: Beecham Group Limited
    Inventors: Martin Cole, Robert A. Edmondson
  • Patent number: 4248966
    Abstract: Isopenicillin derivatives having antimicrobial properties and a general formula of: ##STR1## where R, R.sub.1, and R.sub.2 are hydrogen, methyl, ethyl, propyl, isopropyl, or halogenated methyl, ethyl, propyl or isopropyl radicals and R.sub.3 is ##STR2## are produced in a cell-free system using an extract from Cephalosporium acremonium. The starting materials for the synthesis consist of tripeptides composed of unsubstituted or .beta.-substituted D-valine, unsubstituted or substituted L cysteine, and L- .alpha.-aminoadipic acid or its analogues. Certain enzymes in the cell-free extract are inactivated so that conversion does not proceed past the isopenicillin stage.
    Type: Grant
    Filed: May 17, 1979
    Date of Patent: February 3, 1981
    Assignee: Massachusetts Institute of Technology
    Inventors: Arnold L. Demain, Toshio Konomi, Jack E. Baldwin
  • Patent number: 4208481
    Abstract: Benzylpenicillin is prepared by culturing a penicillin-producing microorganism in a medium containing suitable sources of nitrogen, carbon and energy, and inorganic salts. One or more phenylalkanes of the formula ##STR1## wherein n is an integer from 6 to 13 are included within the medium as the sidechain precursor.
    Type: Grant
    Filed: November 16, 1978
    Date of Patent: June 17, 1980
    Assignee: E. R. Squibb & Sons, Inc.
    Inventors: Laszlo J. Szarka, Robert W. Eltz
  • Patent number: 4183787
    Abstract: A method and apparatus for continuously circulating a mixture comprising a liquid and a gas around a system comprising a riser and a downcomer and a gas disengagement section in which liquid flows downwardly at a velocity which does not exceed 0.2 meters per second and is being injected into a lower section of the riser. The method and apparatus are particularly useful for conducting aerobic fermentations.
    Type: Grant
    Filed: October 25, 1977
    Date of Patent: January 15, 1980
    Assignee: Imperial Chemical Industries Limited
    Inventors: Frank C. Roesler, David A. Hines, Frank P. Maslen, Richard Fawcett