Abstract: A mutant thyroid stimulating hormone receptor (TSHR) or fragment thereof comprises one or more mutations, wherein the mutant TSHR has increased thermostability with respect to the equivalent wild type TSHR or fragment. The one or more mutation is preferably within the extracellular leucine-rich repeat domain (LRD) of the TSHR, or within residues 22 to 260 (TSHR260) of the TSHR, or may be in the transmembrane domain (TMD), A mutant TSHR or fragment thereof of the invention preferably consists of, or consists essentially of, the subdomain TSHR260 of the TSHR receptor. A mutant TSHR or fragment thereof according to the invention has a greater thermostability than the equivalent wild type TSHR or fragment as determined by its half-life at a given temperature, and can be purified whilst retaining activity. A mutant TSHR or fragment thereof according to the invention may also be deglycosylated whilst retaining activity.
Type:
Grant
Filed:
June 11, 2015
Date of Patent:
August 22, 2023
Assignee:
RSR Limited
Inventors:
Bernard Rees Smith, Jadwiga Furmaniak, Jane Sanders, Jennifer Miller-Gallacher
Abstract: A method of screening a sample of body fluid obtained from an animal subject for analyte autoantibodies reactive with one or more antigenic molecules selected from pancreatic islet cell antigenic molecules (GAD, 1A2) and insulin, or one or more variants, analogs, derivatives or fragments thereof, and a kit for use in such a method. After addition of the sample one or more complexes comprising [antigenic molecule of first source]-[analyte auto antibody]-[antigenic molecule of second source]. The antigenic molecule of first source is immobilized to a solid phase, the second is labelled.
Type:
Grant
Filed:
August 19, 2016
Date of Patent:
November 26, 2019
Assignee:
RSR LIMITED
Inventors:
Bernard Rees Smith, Jadwiga Furmaniak, Michael Powell
Abstract: A method of screening a sample of body fluid obtained from an animal subject for analyte autoantibodies reactive with one or more antigenic molecules selected from pancreatic islet cell antigenic molecules (GAD, 1A2) and insulin, or one or more variants, analogs, derivatives or fragments thereof, and a kit for use in such a method. After addition of the sample one or more complexes comprising [antigenic molecule of first source]-[analyte auto antibody]-[antigenic molecule of second source]. The antigenic molecule of first source is immobilized to a solid phase, the second is labeled.
Type:
Grant
Filed:
August 19, 2016
Date of Patent:
November 19, 2019
Assignee:
RSR LIMITED
Inventors:
Bernard Rees Smith, Jadwiga Furmaniak, Michael Powell
Abstract: A method of screening a sample of body fluid obtained from an animal subject for analyte autoantibodies reactive with one or more antigenic molecules selected from pancreatic islet cell antigenic molecules (GAD, 1A2) and insulin, or one or more variants, analogs, derivatives or fragments thereof, and a kit for use in such a method. After addition of the sample one or more complexes comprising `antigenic molecule of fist source!-`analyte auto antibody!-`antigenic molecule of second source! The antigenic molecule of first source is immobilized to a solid phase, the second is labeled.
Type:
Grant
Filed:
March 5, 2012
Date of Patent:
September 6, 2016
Assignee:
RSR Limited
Inventors:
Bernard Rees Smith, Jadwiga Furmaniak, Michael Powell
Abstract: This invention relates to a crystallisable composition comprising a TSHR polypeptide, to crystals comparing a TSHR polypeptide and to TSHR-related applications.
Type:
Grant
Filed:
July 24, 2013
Date of Patent:
September 29, 2015
Assignee:
RSR LIMITED
Inventors:
Jane Sanders, Jadwiga Furmaniak, Barnard Rees Smith
Abstract: A mutated TSHR preparation which includes at least one point mutation characterized in that at least amino acid Arg at a position corresponding to amino acid 255 of a full length human TSHR has been mutated to a different amino acid residue in said mutated TSHR preparation, whereby said mutated TSHR preparation differentially interacts with patient serum stimulating TSHR autoantibodies, patient serum blocking TSHR autoantibodies and TSH, in that (i) the stimulatory effect of patient serum stimulating TSHR autoantibodies interacting with the mutated TSHR preparation is substantially reduced or essentially abolished, when compared to the stimulatory effect of the patient serum stimulating TSHR autoantibodies interacting with a reference TSHR preparation which has an amino acid sequence corresponding to that of said mutated TSHR preparation with the exception that said mutation of Arg at a position corresponding to amino acid 255 of a full length human TSHR is not present in said reference TSHR preparation, (ii)
Type:
Grant
Filed:
August 3, 2005
Date of Patent:
June 2, 2015
Assignee:
RSR Limited
Inventors:
Bernard Rees Smith, Jadwiga Furmaniak, Jane Sanders
Abstract: A binding partner for the TSH receptor, which binding partner comprises, or is derived from, a human monoclonal or recombinant antibody, or one or more fragments thereof, reactive with the TSH receptor, uses thereof, methods of diagnosis and therapy employing the same, and anti-idiotypic antibodies thereto.
Type:
Grant
Filed:
December 29, 2011
Date of Patent:
December 2, 2014
Assignee:
RSR Limited
Inventors:
Jane Sanders, Jadwiga Furmaniak, Bernard Rees Smith
Abstract: The invention provides an isolated antibody for the TSHR which is an antagonist of TSH. The invention also relates to methods of using antibodies of the invention.
Type:
Grant
Filed:
February 14, 2008
Date of Patent:
September 23, 2014
Assignee:
RSR Limited
Inventors:
Bernard Rees Smith, Jadwiga Furmaniak, Jane Sanders
Abstract: A binding partner for the TSH receptor, which binding partner comprises, or is derived from, a human monoclonal or recombinant antibody, or one or more fragments thereof, reactive with the TSH receptor, uses thereof, methods of diagnosis and therapy employing the same, and anti-idiotypic antibodies thereto.
Type:
Grant
Filed:
December 28, 2011
Date of Patent:
June 17, 2014
Assignee:
RSR Limited
Inventors:
Jane Sanders, Jadwiga Furmaniak, Bernard Rees Smith
Abstract: This invention relates to a crystallisable composition comprising a TSHR polypeptide, to crystals comparing a TSHR polypeptide and to TSHR-related applications.
Type:
Application
Filed:
July 24, 2013
Publication date:
March 13, 2014
Applicant:
RSR LIMITED
Inventors:
Jane SANDERS, Jadwiga FURMANIAK, Barnard Rees SMITH
Abstract: The invention provides an isolated antibody for the TSHR which is an antagonist of TSH. The invention also relates to methods of using antibodies of the invention.
Type:
Application
Filed:
February 14, 2008
Publication date:
July 18, 2013
Applicant:
RSR LIMITED
Inventors:
Bernard Rees Smith, Jadwiga Furmaniak, Jane Sanders
Abstract: A binding partner for the TSH receptor, which binding partner comprises, or is derived from, a human monoclonal or recombinant antibody, or one or more fragments thereof, reactive with the TSH receptor, uses thereof, methods of diagnosis and therapy employing the same, and anti-idiotypic antibodies thereto.
Type:
Application
Filed:
December 29, 2011
Publication date:
March 7, 2013
Applicant:
RSR LIMITED
Inventors:
Jane Sanders, Jadwiga Furmaniak, Bernard Rees Smith
Abstract: A binding partner for the TSH receptor, which binding partner comprises, or is derived from, a human monoclonal or recombinant antibody, or one or more fragments thereof, reactive with the TSH receptor, uses thereof, methods of diagnosis and therapy employing the same, and anti-idiotypic antibodies thereto.
Type:
Application
Filed:
December 28, 2011
Publication date:
November 1, 2012
Applicant:
RSR LIMITED
Inventors:
Jane Sanders, Jadwiga Furmaniak, Bernard Rees Smith
Abstract: A method of screening a sample of body fluid obtained from an animal subject for analyte autoantibodies reactive with one or more antigenic molecules selected from pancreatic islet cell antigenic molecules (GAD, 1A2) and insulin, or one or more variants, analogues, derivatives or fragments thereof, and a kit for use in such a method. After addition of the sample one or more complexes comprising `antigenic molecule of fist source!-`analyte auto antibody!-`antigenic molecule of second source! The antigenic molecule of first source is immobilised to a solid phase, the second is labeled.
Type:
Application
Filed:
March 5, 2012
Publication date:
September 6, 2012
Applicant:
RSR Limited
Inventors:
Bernard Rees SMITH, Jadwiga Furmaniak, Michael Powell
Abstract: This invention relates to a crystallisable composition comprising a TSHR polypeptide, to crystals comparing a TSHR polypeptide and to TSHR-related applications.
Type:
Application
Filed:
November 29, 2011
Publication date:
April 12, 2012
Applicant:
RSR LIMITED
Inventors:
JANE SANDERS, JADWIGA FURMANIAK, BARNARD REES SMITH