Patents Assigned to Gist-Brocades
  • Methods and means for controlling the stability of proteins
    Patent number: 5290690
    Abstract: The invention pertains to a method for the production of a biologically active modified protein derived from a starting protein having essentially the same kind of biological activity with an attendant modulation effect on, particularly increase of, the stability as compared with that of the starting protein. The method comprises substituting an arginine residue for a lysine residue of the starting protein at a site that can sterically accommodate the substitution, without substantially altering the biological activity of the starting protein, said site being preferably of low solvent accessibility, at interfaces between domains or sub-units of the starting protein.
    Type: Grant
    Filed: August 25, 1989
    Date of Patent: March 1, 1994
    Assignees: Plant Genetic Systems, Gist-brocades
    Inventors: Nadir Mrabet, Ignace Lasters, Patrick Stanssens, Gaston Matthyssens, Shoshana Wodak, Wilhelmus J. Quax
  • Molecular cloning and expression of gene encoding lipolytic enzyme
    Patent number: 5278066
    Abstract: Novel microbial host strains are provided which are transformed by a vector molecule comprising a DNA fragment encoding a lipolytic enzyme and a marker for selection, capable of producing active lipase. Said DNA fragment is preferably derived from a Pseudomonas species.
    Type: Grant
    Filed: September 25, 1989
    Date of Patent: January 11, 1994
    Assignee: Gist-brocades NV
    Inventors: Peter M. Andreoli, Maria M. J. Cox, Farrokh Farin
  • 6-diazo-penicillanic acid 1,1-dioxide derivatives
    Patent number: 5266693
    Abstract: A process for the preparation of at least one compound of a formula selected from the group consisting of ##STR1## and their salts and esters wherein X is selected from the group consisting of hydrogen and a substituent such as halogen and acetoxy comprising diazotizing a compound of the formula ##STR2## and salts and esters thereof wherein X has the above definition and brominating the resulting diazotized compound with at least an equimolar amount of a nitrosating agent in the presence of 1 to 5 equivalents of a strong acid in solution or suspension in a mixture of water and an at least partially water-miscible organic solvent with the amount of water being 1 to 20% by volume containing at least equimolar amounts of hydrogen bromide and bromine which bromo compounds are useful intermediates for the preparation of penicillanic acid-1,1-dioxide and its derivatives and novel 6-diazo-intermediates.
    Type: Grant
    Filed: May 8, 1992
    Date of Patent: November 30, 1993
    Assignee: Gist-Brocades N.V.
    Inventors: Peter W. Henniger, Johannes K. van der Drift
  • Oral pharmaceutical compositions in unit dosage form
    Patent number: 5264222
    Abstract: Oral pharmaceutical compositions in unit dosage form, especially capsules, comprising solid Colloidal Bismuth Subcitrate (CBS), optionally one or more auxilliary medicaments and excipients, the dosage units having a packing density of between 0.06 and 0.60 grams of CBS per ml.
    Type: Grant
    Filed: July 6, 1992
    Date of Patent: November 23, 1993
    Assignee: Gist-Brocades N.V.
    Inventors: Jan W. Groenendaal, Aart Muhlenbruch
  • Anoxic ammonia oxidation
    Patent number: 5259959
    Abstract: A biological denitrification is provided in which ammonium ion is used as an electron donor in the denitrification. The process may advantageously be used under conditions of high ammonium ion concentrations in waste water or to remove ammonium ion from manure, soil or surface water. Microorganisms are described which may be used in these processes.
    Type: Grant
    Filed: October 25, 1991
    Date of Patent: November 9, 1993
    Assignee: Gist-Brocades N.V.
    Inventor: Arnold Mulder
  • Processing of proteins
    Patent number: 5246838
    Abstract: The subject invention describes the cloning and overexpression of leader peptidase genes. A method for isolating a leader peptidase gene is disclosed. Overexpression of the signal peptidase in a suitable host species leads to an enhanced rate of protein processing.
    Type: Grant
    Filed: February 28, 1991
    Date of Patent: September 21, 1993
    Assignee: Gist-brocades, N.V.
    Inventors: Jan M. Van Dijl, Hilde E. Smith, Sierd Bron, Wilhelmus J. Quax, Gerard Venema
  • Molecular cloning and expression in industrial Bacillus species
    Patent number: 5238833
    Abstract: Novel methods and novel industrial unicellular microorganism strains, particularly industrial Bacillus strains, are provided for enhanced production of endogenous and exogenous polypeptides. Cloning vehicles containing the gene expressing the polypeptide of interest are introduced into a compatible host. Transformed hosts harboring the introduced vehicle in a stable way by integration of the vehicle into the host cells chromosome are selected Efficient transfer of the vehicle containing the gene of interest is achieved, with the resulting industrial strain transformants being effective, stable producers of the desired polypeptide product.
    Type: Grant
    Filed: May 13, 1991
    Date of Patent: August 24, 1993
    Assignee: Gist-brocades, NV
    Inventors: Johan P. M. Sanders, Johannes A. Van Den Berg, Peter M. Andreoli, Yvonne J. Vos, Jan H. Van EE, Leo J. S. M. Mulleners
  • Stabilization of carboxyl esterase
    Patent number: 5238831
    Abstract: Carboxyl esterase is inactivated by several chemical compounds such as naproxen or diclofop. By substituting or modifying certain basic residues of the carboxyl esterase, this enzyme shows improved stability properties during application. In this way it is possible to perform stereospecific hydrolysis reactions on industrial scale even at high substrate concentrations.
    Type: Grant
    Filed: May 14, 1992
    Date of Patent: August 24, 1993
    Assignee: Gist-brocades
    Inventors: Johanna H. G. M. Mutsaers, Cornelis J. van der Laken, Cornelis P. Broekhuizen, Wilhemus J. Quax
  • Substance with interleukin-8 inhibiting activity and process for its preparation
    Patent number: 5234911
    Abstract: A substance is prepared having interleukin-8 inhibiting activity by extracting psoriatic scales and separating the extract on several successive HPLC columns, using an assay for IL-8i activity based on the inhibition of myeloperoxidase release and/or of the neutrophil chemotaxis of a reference sample.The substance is suitable for the preparation of anti-inflammatory medicines.
    Type: Grant
    Filed: January 16, 1991
    Date of Patent: August 10, 1993
    Assignee: Gist-brocades, N.V.
    Inventors: Enno Christophers, Jens-Michael Schroder
  • DNA constructs containing a kluyveromyces .alpha. factor leader sequence for directing secretion of heterologous polypeptides
    Patent number: 5217891
    Abstract: DNA constructs that are useful for providing secretory expression of heterologous polypeptides in yeast comprising a DNA sequence that includes a Kluyveromyces .alpha.-factor leader sequence linked to the heterologous polypeptide by a yeast processing signal. Constructs employing the K. lactis .alpha.-factor leader and processing signal sequences, with and without spacer, linked to prochymosin are exemplified.
    Type: Grant
    Filed: April 9, 1990
    Date of Patent: June 8, 1993
    Assignees: Chiron Corporation, Gist-Brocades
    Inventors: Anthony J. Brake, Johan A. Van Den Berg
  • Molecular cloning and expression of genes encoding proteolytic enzymes
    Patent number: 5217878
    Abstract: Novel methods and novel industrial Bacillus strains are provided for enhanced production of serine protease. Plasmid constructs comprising the serine protease gene are introduced into a compatible host, generally a Bacillus already overproducing serine protease. Preferred host cells are those from Bacillus novo sp. PB92 and the preferred serine protease gene also originates from Bacillus PB92. Integration and maintenance of the plasmid in the host cell chromosome can be achieved by including a temperature sensitive origin of replication in the plasmid construct and growing under selective conditions.
    Type: Grant
    Filed: February 29, 1988
    Date of Patent: June 8, 1993
    Assignee: Gist-Brocades, NV
    Inventors: Christiaan A. G. van Eekelen, Johannes C. van der Laan, Leo J. S. M. Mulleners
  • Secretory signal selection vectors for extracellular protein synthesis in Bacilli
    Patent number: 5212070
    Abstract: Novel vectors are provided for identifying secretory signal sequences from DNA fragments of unicellular microorganisms. The plasmids comprise a multiple cloning site with restriction sites in reading frame with a structural gene which permits rapid screening of the secreted expression product. Optionally, the vectors may include a promoter region upstream from the multiple cloning site. The invention is exemplified with Bacillus. Specific secretory signal sequences have been isolated with those vectors, allowing for efficient secretion into the supernatant, and not just to the periplasmic space to provide proteins in economically high yields. Secretory sequences are provided superior to other previously known sequences.
    Type: Grant
    Filed: December 13, 1990
    Date of Patent: May 18, 1993
    Assignee: Gist-brocades
    Inventors: Hilde E. Smith, Jan H. Van Ee, Ben P. H. Peeters, Sierd Bron, Gerard Venema
  • Pharmaceutical composition and process for its preparation
    Patent number: 5211958
    Abstract: A multi-purpose pharmaceutical tablet which can either be readily swallowed or dissolved in water to give a dispersion, comprising a tetracycline, microcrystalline cellulose or microfine cellulose, low substituted hydroxypropylcellulose and a thickening agent, preferably hydroxypropyl methylcellulose, and optionally other conventional adjuvants. The tablet may be easily swallowed as such, and when immersed in water, it affords a very fine dispersion within 30-60 seconds. The tablet may be prepared by direct compression, or by a wet granulation process in which a granulate is used which contains tetracycline and any substantial amount of a wet binding substance.
    Type: Grant
    Filed: April 29, 1992
    Date of Patent: May 18, 1993
    Assignee: Gist-Brocades, N.V.
    Inventors: Piet J. Akkerboom, Robert De Cocq, Maria Wegman
  • Process for the preparation of difluorobenzamide
    Patent number: 5206158
    Abstract: The invention provides a process for the preparation of 2,6-difluorobenzamide which comprises subjecting 2,6-difluorobenzonitrile to the action of a suitable hydrolysing microorganism or nitrilase extract therefrom; and Rhodococcus Sp. NCIB 12218 or a mutant thereof, suitable for use in the process.
    Type: Grant
    Filed: August 21, 1990
    Date of Patent: April 27, 1993
    Assignees: Gist-Brocades N.V., Shell Internationale Research Maatschappij B.V.
    Inventors: Kenneth H. Clifford, Philip J. Geary, Robert J. Pryce
  • Vectors in use in filamentous fungi
    Patent number: 5198345
    Abstract: Novel vectors are disclosed for use in filamentous fungi such as Aspergillus sp. in particular, whereby protein coding regions may be inserted therein to achieve expression or expression followed by secretion of the coded protein from the host. Signal peptide sequences and promoter sequences valuable for this purpose are disclosed as are expression vectors containing coding regions native or foreign to the fungal host. In accordance with the invention, a filamentous fungus such as Aspergillus may be provided with foreign or natural coding regions associated with foreign or natural promoter sequences and optionally signal peptide sequences which can be used to control the expression and/or secretion of the proteins encoded by these coding regions.
    Type: Grant
    Filed: December 20, 1985
    Date of Patent: March 30, 1993
    Assignee: Gist-Brocades N.V.
    Inventors: David I. Gwynne, Francis P. Buxton, Mark H. Pickett, Roger W. Davies, Claudio Scazzocchio
  • 9.alpha.-hydroxy-17-methylene steroids, process for their preparation and their use in the preparation of corticosteroids
    Patent number: 5194602
    Abstract: New 9.alpha.-hydroxy-17-methylene steroids are prepared by the introduction of a substituted 17-methylene group in 9.alpha.-hydroxyandrost-4-ene-3, 17-dione.The resulting compounds are useful starting compounds in the synthesis of corticosteroids.
    Type: Grant
    Filed: December 12, 1990
    Date of Patent: March 16, 1993
    Assignee: Gist-Brocades N.V.
    Inventors: Jacobus N. M. Batisi, Arthur F. Marx
  • Saccharomyces strains for maltose fermentation
    Patent number: 5190877
    Abstract: Methods and compositions are provided relating to yeasts capable of improved fermentation of sugars. Particularly, genes from the MAL locus are used for transformation of yeast hosts, where the genes are under the wild-type promoter or a strong promoter which provides for regulatable or constitive expression under the conditions of fermentation. Particularly, the yeast hosts find use in the leavening of dough.
    Type: Grant
    Filed: November 13, 1990
    Date of Patent: March 2, 1993
    Assignee: Gist-brocades N.V.
    Inventors: Klaas A. Osinga, Robert F. Beudeker, Johannes B. Van der Platt, Johannes A. de Hollander
  • Proteins with factor VIII activity: process for their preparation using genetically-engineered cells and pharmaceutical compositions containing them
    Patent number: 5171844
    Abstract: Novel polypeptides having Factor VIII activity are provided as well as compositions and methods for their preparation. The polypeptides comprise derivatives and fragments of Factor VIII and have sequences substantially similar to portions of naturally occuring Factor VIII. The polypeptides find use in treatment of Hemophilia A.
    Type: Grant
    Filed: June 10, 1988
    Date of Patent: December 15, 1992
    Assignee: Gist-Brocades N.W.
    Inventors: Albert J. J. van Ooyen, Hans Pannekoek, Martinus P. Verbeet, Robert W. van Leen
  • Penicillin G acylase, a gene encoding the same and a method for the production of this enzyme
    Patent number: 5168048
    Abstract: The invention provides a gene encoding penicillin G acylase, the enzyme encoded by said gene and a method for the production of said enzyme by incorporating said gene in a host and bringing the same to expression. The gene is preferably obtained from a strain of the microorganism Alcaligenes faecalis.
    Type: Grant
    Filed: April 18, 1991
    Date of Patent: December 1, 1992
    Assignee: Gist-brocades NV
    Inventor: Wilhelmus J. Quax
  • Microbiological preparation of 9-alpha-hydroxy-17-keto steroids
    Patent number: 5166055
    Abstract: 9.alpha.-hydroxy-17-keto steroids are prepared by fermenting steroids having a C-17-side chain of 5-10 carbon atoms inclusive, with the novel Mycobacterium species CBS 482.86.Starting from various substrates containing a 5-10 C carbon chain on C-17, 9.alpha.-hydroxyandrost-4-ene-3,17-dione, 7.alpha.,9.alpha.,12.alpha.-trihydroxyandrost-4-ene-3,17-dione or 9.alpha.-hydroxyandrost-4,11-diene-3,17-dione is obtained in high yield.The resulting compounds are useful intermediates in the synthesis of therapeutically important steroids, particularly corticosteroids.
    Type: Grant
    Filed: July 15, 1991
    Date of Patent: November 24, 1992
    Assignee: Gist-Brocades N.V.
    Inventors: Harmen Slijkhuis, Arthur F. Marx