Preparing Compound Having A 1-thia-4-aza-bicyclo (3.2.0) Heptane Ring System (e.g., Penicillin, Etc.) Patents (Class 435/43)
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Patent number: 5215891Abstract: 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: GrantFiled: March 9, 1992Date of Patent: June 1, 1993Assignee: Farmitalia Carlo ErbaInventors: Maria Altamura, Pietro Cesti, Franco Francalanci, Marcello Marchi, Marco Foa', Stefano Cambiaghi, Franco Dallatomasina
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Patent number: 5079146Abstract: 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: GrantFiled: April 4, 1989Date of Patent: January 7, 1992Assignee: Sclavo S.p.A.Inventors: Claudio Fuganti, Eva Baldaro, Daniela Faiardi, Ameriga Lazzarini
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Patent number: 5013452Abstract: 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: GrantFiled: December 4, 1989Date of Patent: May 7, 1991Assignee: Petrolite CorporationInventors: Thomas J. Bellos, Richard D. Keating
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Patent number: 5008188Abstract: 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: GrantFiled: November 4, 1987Date of Patent: April 16, 1991Assignee: Nippon Zeon Co., Ltd.Inventors: Hideaki Yamada, Yoshiki Tani, Sakayu Shimizu, Shozo Shiozaki
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Patent number: 4980284Abstract: 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: GrantFiled: May 25, 1990Date of Patent: December 25, 1990Assignee: Degussa AGInventors: Kyriakos Makryaleas, Karlheinz Drauz
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Patent number: 4980282Abstract: 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: GrantFiled: November 19, 1987Date of Patent: December 25, 1990Assignee: CPC International Inc.Inventors: Jean-Claude de Troostembergh, Francoise Oudeene
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Patent number: 4865973Abstract: 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: GrantFiled: August 13, 1986Date of Patent: September 12, 1989Assignee: Queen's University at KingstonInventors: Finn Kollerup, Andrew J. Daugulis
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Patent number: 4847200Abstract: 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: GrantFiled: September 5, 1986Date of Patent: July 11, 1989Assignee: Queen's University at KingstonInventors: Saul Wolfe, Donald Westlake, Susan Jensen
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Patent number: 4769325Abstract: 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: GrantFiled: July 28, 1986Date of Patent: September 6, 1988Inventors: Jack E. Baldwin, Amit Basak
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Patent number: 4732851Abstract: 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: GrantFiled: February 10, 1983Date of Patent: March 22, 1988Assignee: Purification Engineering, Inc.Inventors: Louis L. Wood, Gary J. Calton
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Patent number: 4722924Abstract: 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: GrantFiled: August 22, 1985Date of Patent: February 2, 1988Assignee: National Research Development CorporationInventor: Jack E. Baldwin
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Patent number: 4710457Abstract: 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: GrantFiled: June 29, 1983Date of Patent: December 1, 1987Assignee: Sloan-Kettering Institute for Cancer ResearchInventors: Bo Dupont, Yasuo Morishima, Nancy Collins, Shun-ichiro Ogata, Kenneth O. Lloyd
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Patent number: 4709015Abstract: 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: GrantFiled: August 9, 1984Date of Patent: November 24, 1987Assignee: Ortho Pharmaceutical CorporationInventors: Patrick C. Kung, Gideon Goldstein
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Patent number: 4693977Abstract: 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: GrantFiled: January 23, 1986Date of Patent: September 15, 1987Assignee: Queen's University at KingstonInventors: Saul Wolfe, Donald Westlake, Susan Jensen
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Patent number: 4666835Abstract: 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: GrantFiled: April 29, 1986Date of Patent: May 19, 1987Inventor: Jack E. Baldwin
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Patent number: 4661586Abstract: 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: GrantFiled: December 2, 1983Date of Patent: April 28, 1987Assignee: The Board of Trustees of the Leland Stanford Junior UniversityInventors: Ronald Levy, Jeanette Dilley, David G. Maloney, Richard A. Miller
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Patent number: 4650755Abstract: 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: GrantFiled: August 14, 1984Date of Patent: March 17, 1987Assignee: Purification Engineering, Inc.Inventors: Louis L. Wood, Gary J. Calton
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Patent number: 4564444Abstract: 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: GrantFiled: July 26, 1984Date of Patent: January 14, 1986Assignee: Hitachi, Ltd.Inventors: Masakatsu Hiraoka, Kazushi Tsumura, Kenji Baba, Shunsuke Nogita, Shunji Mori
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Patent number: 4536476Abstract: 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: GrantFiled: June 27, 1983Date of Patent: August 20, 1985Assignee: Queen's University at KingstonInventors: Saul Wolfe, Donald Westlake, Susan Jensen
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Patent number: 4510246Abstract: 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: GrantFiled: August 23, 1982Date of Patent: April 9, 1985Assignee: Queen's University at KingstonInventors: Saul Wolfe, Donald Westlake, Susan Jensen
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Patent number: 4413056Abstract: 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: GrantFiled: October 19, 1981Date of Patent: November 1, 1983Assignee: Beecham Group LimitedInventors: Ian R. Chester, Lawson W. Powell, David G. Roberts
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Patent number: 4359528Abstract: 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: GrantFiled: August 28, 1980Date of Patent: November 16, 1982Assignee: Roquette FreresInventors: Francis Devos, Patrick Beuque, Michel Huchette
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Patent number: 4347314Abstract: 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: GrantFiled: May 13, 1980Date of Patent: August 31, 1982Assignee: Beecham Group LimitedInventors: Martin Cole, Robert A. Edmondson
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Patent number: 4346168Abstract: 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: GrantFiled: May 13, 1980Date of Patent: August 24, 1982Assignee: Beecham Group LimitedInventors: Martin Cole, Robert A. Edmondson
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Patent number: 4248966Abstract: 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: GrantFiled: May 17, 1979Date of Patent: February 3, 1981Assignee: Massachusetts Institute of TechnologyInventors: Arnold L. Demain, Toshio Konomi, Jack E. Baldwin
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Patent number: 4208481Abstract: 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: GrantFiled: November 16, 1978Date of Patent: June 17, 1980Assignee: E. R. Squibb & Sons, Inc.Inventors: Laszlo J. Szarka, Robert W. Eltz
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Patent number: 4183787Abstract: 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: GrantFiled: October 25, 1977Date of Patent: January 15, 1980Assignee: Imperial Chemical Industries LimitedInventors: Frank C. Roesler, David A. Hines, Frank P. Maslen, Richard Fawcett