Abstract: Described are new glycoprotein hormones capable of competing with natural hormones for the normal receptor binding sites but substantially incapable of effecting post receptor activities. The glycoprotein hormones of the present invention have had specific (rather than all) oligosaccharide chains removed so as to effectively diminish biologic activity while not significantly reducing plasma half-life, thus improving the molecules effectiveness as an antagonist compared with conventionally-produced molecules. The preferred glycoprotein hormones are ideally obtained by site-directed mutagenesis to selectively deglycosylate the protein. Also described are therapeutic treatments comprising the administration of the recombinant glycoprotein hormones of the present invention as hormone antagonists.
Type:
Grant
Filed:
May 16, 1995
Date of Patent:
June 3, 1997
Assignee:
Applied Research Systems ARS Holding N.V.
Abstract: A method for improving measurement precision in an optical biosensor assay for a ligand in a sample is described. The method involves referencing the assay with an artificially raised background level by the labelling of the optical waveguide with an appropriate reference reagent. Devices for use in such a method are also described.
Type:
Grant
Filed:
December 12, 1994
Date of Patent:
May 20, 1997
Assignee:
Applied Research Systems ARS Holding N.V.
Abstract: An anti-foam device for a bioreactor is provided consisting of a perforated plate, made by hydrophobic material, which rotates at the surface of the liquid culture medium contained in the bioreactor vessel, the perforated plate being perpendicular to an inclination from 45 to 90 degrees in respect of the surface of the culture medium.
Type:
Grant
Filed:
December 8, 1995
Date of Patent:
March 18, 1997
Assignee:
Applied Research Systems Ars Holding N.V.
Abstract: The present invention relates to a macromolecule of proteinaceous nature which activates sperm motility, a process for the preparation thereof by purification of the macromolecule from extracellular fluids, pharmaceutical preparations containing the macromolecule and antibodies directed against determinants specific to the macromolecule and the use thereof as a method to assay the potential fertility of sperm.
Type:
Grant
Filed:
August 18, 1993
Date of Patent:
September 26, 1995
Assignees:
Eva Akerlof, Ake Pousette, Applied Research Systems ARS Holding N.V.
Abstract: The invention concerns a method of homogeneous immunoassay of a ligand in a liquid test sample which comprises: a)incubating a mixture of (1) the liquid test sample; (1i) where the ligand under assay has only one epitope, a covalent conjugate of the ligand with any mono- or poly-epitope molecule having at least one epitope distinct from the epitope of the ligand; (2) a labile enzyme; (3) a first bispecific monoclonal antibody protecting the activity of the encyme through binding to a first epitope on the encyme and capable of binding the ligand under assay; and (4) a second bispecific monoclonal antibody capable of bonding said enzyme and a second distinct epitope on the ligand under assay or an epitope of the said covalent conjugate; whereby a quaternary immunocomplex is formed; b) after incubation, subjecting the mixture to conditions whereby any enzyme not present in such a quaternary immunocomplex is inactivated; and c) determining the amount of detectable encyme, the determination being related to the am
Type:
Grant
Filed:
August 7, 1991
Date of Patent:
May 16, 1995
Assignee:
Applied Research Systems ARS Holding N.V.
Abstract: The invention relates to a method of reducing scattering of light emerging from an optical edge of an optical waveguide. According to the invention, the optical edge is maintained in intimate contact with an index matching substance which itself also forms or intimately contacts a further optical component. The invention also relates to a disposable holder suitable for use in the method.
Type:
Grant
Filed:
October 5, 1992
Date of Patent:
November 29, 1994
Assignee:
Applied Research System Ars Holding N.V.
Abstract: Described are new glycoprotein hormones capable of competing with natural hormones for the normal receptor binding sites but substantially incapable of effecting post receptor activities. The glycoprotein hormones of the present invention have had specific (rather than all) oligosaccharide chains removed so as to effectively diminish biologic activity while not significantly reducing plasma half-life, thus improving the molecules effectiveness as an antagonist compared with conventionally-produced molecules. The preferred glycoprotein hormones are ideally obtained by site-directed mutagenesis to selectively deglycosylate the protein. Also described are therapeutic treatments comprising the administration of the recombinant glycoprotein hormones of the present invention as hormone antagonists.
Type:
Grant
Filed:
September 23, 1993
Date of Patent:
October 4, 1994
Assignee:
Applied Research Systems ARS Holding N.V.
Abstract: The invention relates to a device for use in optical methods of assay. The device comprises an optical structure comprising a dielectric substrate (2) and a thin film waveguide (5), between which is interposed a buffer layer (4). The waveguide carries a layer (10) of reagent suitable for a desired assay. The invention also relates to methods of using the device in an assay.
Type:
Grant
Filed:
May 21, 1991
Date of Patent:
September 6, 1994
Assignee:
Applied Research Systems ARS Holding N.V.
Abstract: The present invention relates to a macromolecule of proteinaceous nature which activates sperm motility, a process for the preparation thereof by purification of the macromolecule from extracellular fluids, pharmaceutical preparations containing the macromolecule and antibodies directed against determinants specific to the macromolecule and the use thereof as a method to assay the potential fertility of sperm.
Type:
Grant
Filed:
November 27, 1991
Date of Patent:
April 19, 1994
Assignees:
Eva Akerlof, Ake Pousette, Applied Research Systems ARS Holding N.V.
Abstract: Normally transcriptionally silent genes in a cell line or microorganism may be activated for expression by inserting a DNA regulatory element which is capable of promoting the expression of a normally expressed gene product in that cell or which is promiscuous, the regulatory element being inserted so as to be operatively linked with the normally silent gene in question. The insertion is accomplished by means of homologous recombination by creating a DNA construct including a segment having a DNA segment of the normally silent gene (targeting DNA) and the DNA regulatory element to induce gene transcription. The technique is also used to modify the expression characteristics of any endogenous gene of a given cell line or microorganism.
Type:
Grant
Filed:
May 28, 1992
Date of Patent:
December 21, 1993
Assignee:
Applied Research Systems Ars Holding N.V.
Abstract: A therapy kit for inducing human ovulation is disclosed. The kit comprises, in separate containers, at least two recombinant FSH isoforms having significantly different plasma half-lives. The FSH isoforms are administered sequentially, beginning with the isoform having the longer plasma half-life.
Type:
Grant
Filed:
August 28, 1991
Date of Patent:
November 16, 1993
Assignee:
Applied Research Systems ARS Holding N.V.
Abstract: Described are new glycoprotein hormones capable of competing with natural hormones for the normal receptor binding sites but substantially incapable of effecting post receptor activities. The glycoprotein hormones of the present invention have had specific (rather than all) oligosaccharide chains removed so as to effectively diminish biologic activity while not significantly reducing plasma half-life, thus improving the molecules effectiveness as an antagonist compared with conventionally-produced molecules. The preferred glycoprotein hormones are ideally obtained by site-directed mutagenesis to selectively deglycosylate the protein. Also described are therapeutic treatments comprising the administration of the recombinant glycoprotein hormones of the present invention as hormone antagonists.
Type:
Grant
Filed:
December 21, 1987
Date of Patent:
November 9, 1993
Assignee:
Applied Research Systems ARS Holding N.V.
Abstract: The present invention relates to a method of controlling gonadotropin levels in mammals which comprises administering a gonadotropin releasing hormone (GnRH) antagonist in an amount and frequency effective to substantially suppress endogenous gonadotropin levels in said mammal and administering gonadotropin releasing hormone (GnRH) in an amount and frequency effective to induce secretion of gonadotropins to maintain a desired level in said mammal. This method is especially useful for treating mammals, particularly women, who suffer from polycystic ovarian disease or hyperandrogenism, or who otherwise have abnormally high levels of luteinizing hormone which it is desired to reduce to approximately normal levels. The method of this invention is particularly advantageous for inducing ovulation in mammals, particularly women, that have the above-mentioned problems. The preferred GnRH antagonists for use in the present invention include Antide and its analogs, which exhibit long term gonadotropin suppression.
Type:
Grant
Filed:
June 14, 1990
Date of Patent:
January 19, 1993
Assignee:
Applied Research Systems ARS Holding N.V.
Abstract: A method for determining whether an infertile patient is likely to benefit from combined GH/gonadotropin or GHRH/gonadotropin therapy comprising the steps of (1) administering a predetermined dose of clonidine or a pharmaceutically acceptable derivative thereof to the patient; (2) monitoring the blood level of GH following the administration of clonidine or a derivative thereof; and (3) detecting whether the peak blood level of GH is above a predetermined level.
Type:
Grant
Filed:
October 1, 1990
Date of Patent:
December 29, 1992
Assignee:
Applied Research Systems ARS Holding N.V.
Abstract: The invention relates to a method of optical analysis which can advantageously be used in conjunction with optical assay techniques, particularly those wherein evanescent signals are to be analysed. The method makes use of the properties of an optical structure (described herein) which allows easy angular discrimination of optical signals emerging from a test object. The invention also relates to apparatus for use in said methods.
Type:
Grant
Filed:
December 19, 1990
Date of Patent:
November 24, 1992
Assignee:
Applied Research Systems ARS Holding, N.V.
Abstract: The cloning and characterization of a newly isolated gene, referred to as saf (secondary metabolism activation factor) is disclosed. This gene encodes a new amino acid polypeptide, referred to as the SAF polypeptide, which directly or indirectly modulates the expression of extracellular enzymes in Steptomyces. DNA units or fragments which encode the SAF polypeptide are also disclosed, as are vectors containing said DNA, host organisms transformed with such vectors, and processes for preparing extracellular enzymes or heterologous polypeptides by culturing such host organisms.
Type:
Grant
Filed:
May 19, 1989
Date of Patent:
June 16, 1992
Assignee:
Applied Research Systems ARS Holding N.V.
Inventors:
Antonio D. Ortega, Jose A. Gil, Tomas V. Garcia, Juan F. Martin
Abstract: Obese patients may be effectively treated by cojointly administering an alpha-2-adrenergic agonist, such as clonidine, and a growth hormone releasing peptide, such as GHRH, to restore or substantially enhance growth hormone release in such patients.
Type:
Grant
Filed:
September 10, 1990
Date of Patent:
June 9, 1992
Assignee:
Applied Research Systems ARS Holding N.V.
Abstract: The cloning and characterization of a newly isolated gene, referred to as saf (secondary metabolism activation factor) is disclosed. This gene encodes a new amino acid polypeptide, referred to as the SAF polypeptide, which directly or indirectly modulates the expression of extracellular enzymes in Streptomyces. DNA units or fragments which encode the SAF polypeptides are also disclosed, as are vectors containing said DNA, host organisms transformed with such vectors, and processes for preparing extracellular enzymes or heterologous polypeptides by culturing such host organisms.
Type:
Grant
Filed:
September 22, 1989
Date of Patent:
June 2, 1992
Assignee:
Applied Research Systems ARS Holding N.V.
Inventors:
Antonio D. Ortega, Jose A. Gil, Tomas V. Garcia, Juan F. Martin
Abstract: The present invention relates to dual analyte enzyme immunoassays for assaying two antigens in a single liquid sample wherein the two immunoreactions are carried out simultaneously and wherein subsequently the two enzyme reactions occur simultaneously. Suitable enzyme/substrate pairs are beta-galactosidase/nitrophenyl-beta-D-galactoside (p- an/or o-) and alkaline phosphatase/phenolphthalein monophosphate.
Type:
Grant
Filed:
March 2, 1987
Date of Patent:
April 28, 1992
Assignee:
Applied Research Systems ARS Holding N.V.