Abstract: Use of .alpha.-hydroxy acids and poly-.alpha.-hydroxy acids as spacer between a therapeutically and/or diagnostically active compound and a soluble macromolecular carrier in pharmaceutical compositions having site-specific delivery. In one embodiment glycolic acid, L-lactic acid or tetra-L-lactic acid is used as spacer between a non-steroidal anti-inflammatory substance and a carrier of low molecular protein (LMWP).
Type:
Grant
Filed:
November 4, 1994
Date of Patent:
May 19, 1998
Assignee:
Rijksuniversiteit Groningen
Inventors:
Erik J. F. Franssen, Frits Moolenaar, Dirk K. F. Meijer, Dick De Zeeuw
Abstract: The system relates to a system for determining a composition of radionuclides in, for instance, a mineral-containing material by detecting gamma and/or X-ray radiation emitted by the nuclides. To that end, the system comprises a detector unit (2,6, 10) which supplies an electrical signal containing information about the intensity and energy of the emitted radiation and a signal processing system by which these electrical signals are further processed for determining the composition mentioned. According to the invention, the signal processing system further comprises an A/D converter (14) to which the electrical signals are applied and a first computer unit (26) which further processes signals supplied by the A/D converter for the purpose of determining the composition mentioned.
Abstract: Induction of an antigen-specific T-lymphocyte response in a T-lymphocyte culture, e.g. a primary cytotoxic T-lymphocyte (CTL) response, by loading antigen-presenting vehicles which carry empty MHC molecules with an antigen-derived T-cell-immunogenic MHC-binding peptide, culturing T-lymphocytes in the presence of the peptide-loaded antigen-presenting vehicles under specific T-lymphocyte response-inducing conditions. Optionally, an antigen-specific T-lymphocyte is isolated from the resulting culture and cultured. The process can be used for preparing CTL which are specific for viral or other foreign antigens, or CTL which are specific for autologous peptides. The process can also be used for the identification of peptides that are capable of binding to MHC and inducing a T cell response.
Type:
Grant
Filed:
May 26, 1992
Date of Patent:
March 24, 1998
Assignees:
Rijksuniversiteit Leiden, Seed Capital Investments (SCI) B.V.
Abstract: A peptide comprising an amino acid sequence derived from human p53 protein, wherein said amino acid sequence has the ability to bind to a human MHC Class I molecule. Its use in prophylactic or therapeutic treatment of diseases such as human cancers showing p53 protein overexpression, and its use in induction of primary p53-specific T cells that can be used in therapeutic treatment. Its use in diagnostic tests or assays.
Type:
Grant
Filed:
February 6, 1995
Date of Patent:
October 21, 1997
Assignees:
Rijksuniversiteit Leiden, Seed Capital Investments, (SCI) B.V.
Inventors:
Cornelis Joseph Maria Melief, Wybe Martin Kast
Abstract: The invention relates to a method for modifying at least a part of the surface of a fluorine-containing plastic, which comprises making the surface hydrophobic by 1) ion-etching the plastic surface; and 2) subsequently treating the plastic surface with flow discharging. The invention also relates to a fluorine-containing plastic having a surface which is at least partially hydrophobe-modified by ion-etching followed by glow discharging, and to materials, such as bio-materials, in which the plastic is incorporated.
Type:
Grant
Filed:
March 15, 1994
Date of Patent:
October 21, 1997
Assignee:
Rijksuniversiteit Groningen
Inventors:
Josephus Maria Schakenraad, Hendrik Jan Busscher
Abstract: The invention relates to a biodegradable chewing gum comprising one or more conventional chewing gum components and as gum base at least one biodegradable polymer selected from the group of polyesters and polycarbonates.
Type:
Grant
Filed:
October 13, 1995
Date of Patent:
September 30, 1997
Assignee:
Rijksuniversiteit te Groningen
Inventors:
Dirk Wybe Grijpma, Johannes Fredericus Laimbock, Albert Johan Pennings
Abstract: Plants are provided with improved resistance against pathogenic fungi. They are genetically transformed with one or more polynucleotides which essentially comprise one or more genes encoding plant chitinases and .beta.-1,3-glucanases. Preferred are the intracellular forms of the said hydrolytic enzymes, especially preferred are those forms which are targeted to the apoplastic space of the plant by virtue of the modification of the genes encoding the said enzymes. Particularly preferred are plants exhibiting a relative overexpression of at least one gene encoding a chitinase and one gene encoding a .beta.-1,3-glucanase.
Type:
Grant
Filed:
April 19, 1993
Date of Patent:
September 23, 1997
Assignees:
MOGEN International, n.v., Rijksuniversiteit te Leiden
Inventors:
Bernardus J. C. Cornelissen, Leo Sjoerd Melchers, Elisabeth J. S. Meulenhoff, Jeroen S. C. van Roekel, Marianne Beatrix Sela-Buurlage, Alexandra Aleida Vloemans, Charles Peter Woloshuk, John Ferdinand Bol, Hubertus J. M. Linthorst
Abstract: The present invention relates to various functional variants of recombinant protein S (PS) that do not significantly bind C4b binding protein (C4BP) and uses of the variants as a therapeutic reagent. In particular the invention is directed at deletion mutants of protein S, having cofactor activity toward APC and lacking at least the two postulated C4BP binding domains of the SHBG-like domain of the corresponding mature wild type protein S. Such a deletion mutant in particular lacks at least amino acid residues 401-457 and 583-635 of the corresponding mature wild type human protein S.
Abstract: The present invention relates to various functional variants of recombinant protein S (PS) that do not significantly bind C4b binding protein (C4BP) and uses of the variants as a therapeutic reagent. In particular the invention is directed at deletion mutants of protein S, having cofactor activity toward APC and lacking at least the two postulated C4BP binding domains of the SHBG-like domain of the corresponding mature wild type protein S. Such a deletion mutant in particular lacks at least amino acid residues 401-457 and 583-635 of the corresponding mature wild type human protein S.
Abstract: In a process and devices or continuously measuring the concentration of an analyte in tissue. The tissue is provided with a hollow fiber having a pore size between the size of the analyte and the size of macromolecules, hollow fiber is perfused with a solution compatible with the tissue, and that solution is supplied from the hollow fiber through a reactor for the analyte. The reactor has a second hollow fiber having a pore size between the size of the analyte and the size of macromolecules, and the second hollow fiber is located in a container which contains macromolecular reactants for detecting the analyte and a signal producing system coupled therewith. The perfusion fluid is fed from the reactor to an eliminator for the analyte, whereby at least 95% of the remaining analyte is removed from the perfusion fluid and the perfusion fluid is reintroduced into said first hollow fiber.
Type:
Grant
Filed:
July 11, 1996
Date of Patent:
April 1, 1997
Assignees:
Siemens-Elema AB, Rijksuniversiteit te Groningen
Inventors:
Adelbert J. M. Schoonen, Fransiscus J. Schmidt, Klaas-Jan C. Wientjes
Abstract: Pt-containing compound with the formula {Pt.sup.II (w)(x)(y)(z)} or {Pt.sup.IV (u)(v)(w)(x)(y)(z)}, wherein u, v, w, x, y and z represent whether or not the same whether or not interconnected ligands, of which at least one is a leaving ligand and at least one of the remaining ligands represents a detectable marker group. According to the invention (CH.sub.3).sub.2 SO, Cl or H.sub.2 O appears to be suitable as a leaving ligand while as detectable marker group a fluorescent group merits preference and is the ligand fluorescein or tetramethyl rhodamine. A suitable Pt-containing compounds is {Pt(ethylenediamine)(Me.sub.2 SO)(fluorescein-NH(CS)-NHCH.sub.3)} (PtF). Further, the invention comprises a process for the preparation of the Pt-containing compounds, where the Pt-containing compounds are prepared in a manner known per se for analogous compounds.
Type:
Grant
Filed:
October 29, 1993
Date of Patent:
December 3, 1996
Assignees:
Stichting Klinische Research Academisch Medisch Centrum, Rijksuniversiteit Leiden
Inventors:
Franciscus M. van den Berg, Edwin L. M. Lempers, Marieke J. Bloemink, Jan Reedijk
Abstract: The present invention provides a method for site-directed integration of DNA-sequences into the genome of plants via homologous recombination, by transforming said plants using the DNA-transfer system of Agrobacterium, in which the transforming DNA comprises in its most simple form a region homologous to the target locus, as well as a region which is different from the target locus either next to one or between two T-DNA borders.
Type:
Grant
Filed:
July 6, 1993
Date of Patent:
March 26, 1996
Assignee:
Mogen International, n.v./Rijksuniversiteit te Leiden
Inventors:
Remko Offringa, Marcellus J. A. De Groot, Paul J. J. Hooykaas, Petrus J. M. Van Den Elzen
Abstract: A copolymer of a lactone and a polycyclic carbonate is prepared by heating a monomer of a lactone with a polycyclic carbonate having two cyclic structures including a carbonate group at elevated temperatures less than 200 degrees Centigrade in the presence of a catalyst. The described copolymers evidence excellent mechanical properties, good resorption velocity and do not disintegrate upon degradation into materials of high crystallinity.
Type:
Grant
Filed:
June 17, 1994
Date of Patent:
February 20, 1996
Assignee:
Rijksuniversiteit te Groningen
Inventors:
Dirk W. Grijpma, Erik Kroeze, Atze J. Nijenhuis, Albertus J. Pennings
Abstract: The invention relates to a process for the incorporation of foreign DNA into chromosomes of dicotyledonous plants by infecting the plants or incubating plant protoplasts with Agrobacterium bacteria, which contain one or more plasmids, wherein bacteria are used which contain at least one plasmid having the vir-region of Ti (tumor inducing) plasmid but no T-region, and at least one other plasmid having a T-region with incorporated therein foreign DNA but no vir-region, as well as to a Agrobacterium bacteria, suitable for use in the process according to claim 1 wherein at least one plasmid which has the vir-region of a Ti (tumor inducing) plasmid but no T-region and at least one other plasmid which has a wild type T-region with incorporated in it foreign DNA but no vir-region.
Abstract: The invention relates to a microbiological process for the production of polyesters and utilizes bacteria of the Pseudomanas fluorescens rRNA branch according to the phylogenetic classification of De Vos and De Ley. These bacteria are cultured under aerobic fermentation conditions in a nutrient medium comprising an excess of at least one assimilarable acylic aliphatic hydrocarbon compound having 6-18 carbon atoms and a limiting quantity of at least one of other nutrients essential for growth to form poly-3-hydroxyalkanaoates.
Type:
Grant
Filed:
October 24, 1991
Date of Patent:
September 6, 1994
Assignee:
Rijksuniversiteit te Groningen
Inventors:
Bernard Witholt, Gerrit Eggink, Gjalt W. Huisman
Abstract: This invention relates to a process for producing polyester biopolymers by culturing Pseudomonas oleovorans bacteria on substrates comprising certain nutrients. The nature of the polyesters can be varied by varying the nature of the carbon source used. In this way polyesters with unsaturated double bonds can be produced, too. From the polyesters, optically active carboxylic acids or esters are produced. The polymers can be used for making articles of manufacture, such as sutures, films, skin and bone grafts.
Abstract: The invention relates to an antimicrobial composition on the basis of a physiologically acceptable varnish dissolved therein an antimicrobial agent, preferably chlorhexidine, in an amount sufficient for elimination of Streptococcus mutans in one treatment. This composition can be applied on the tooth surface and other surfaces, such as the skin or on medical instruments.
Type:
Grant
Filed:
May 18, 1992
Date of Patent:
January 12, 1993
Assignees:
Explore, Rijksuniversiteit te Groningen
Inventors:
Mathias J. M. Schaeken, Johannes S. Van der Hoeven, Pieter De Haan, Coenraad F. Lerk
Abstract: A wearable-type glucose sensor for continuously or intermittently determining the glucose content comprises a short hollow fiber (2) to be positioned in the subcutaneous tissue. This hollow fiber is connected via tubes (3,4) with component parts (5 . . . 12) located outside the body, such as a measuring unit (11). When a perfusion fluid containing the enzyme glucose oxidase is passed through the hollow fiber, a subcutaneous dialysis will take place in which some glucose dissolves in the perfusion fluid through the wall of the hollow fiber. This glucose is completely oxidized by the oxygen dissolved in the perfusion fluid in the presence of the glucose oxidase. By means of the measuring unit the resultant amount of H.sub.2 O.sub.2 or, preferably, the employed amount of O.sub.2 is determined, both of which are a measure of the subcutaneous glucose concentration.
Type:
Grant
Filed:
May 15, 1990
Date of Patent:
December 29, 1992
Assignee:
Rijksuniversiteit te Groningen
Inventors:
Adelbert J. M. Schoonen, Franciscus J. Schmidt
Abstract: This invention relates to a process for the microbiological production of compounds containing a terminal hydroxyl or epoxy group from an aliphatic substrate or a substrate with an aliphatic side chain, using microorganisms genetically engineered so that they have retained their capacity to perform the terminal oxidation of the substrate, but are no longer able to convert the resulting oxidation product further to any significant extent. Preferred substrates are n-alkanes, n-alkenes, and n-alkadienes containing 6-12 carbon atoms. Preferred micro-organisms are genetically engineered Pseudomonas oleovorans and Pseudomonas putida strains lacking an active plasmidic alkanol-dehydrogenase gene. The invention also relates to micro-organisms thus genetically engineered.