Rsr Limited

Jadwiga Furmaniak

Bernard Rees Smith

Jane Sanders

Michael Powell

Bernard Rees-Smith

Barnard Rees Smith

Jennifer Miller-Gallacher

Jane Fina Sanders

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. Methods, kits and uses employing the mutant TSHR or fragment thereof according to the invention are also provided.

Glycoprotein hormone receptor mutations

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.

Detection of autoantibodies reactive with pancreatic islet cell antigenic molecules and/or insulin

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.

According to one aspect there is provided An isolated human antibody molecule which binds to the TSHR and which reduces ligand-induced stimulation of the TSHR but has no effect on TSHR constitutive activity wherein the isolated human antibody molecule has the characteristic of patient serum TSHR autoantibodies of inhibiting TSH and M22 binding to the TSHR.

Human anti TSHR antibodies

The present invention is concerned with epitope regions of a thyrotrophin (TSH) receptor, uses thereof and antibodies thereto.

Epitope regions of a thyrotrophin (TSH) receptor, uses thereof and antibodies thereto

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 &grave;antigenic molecule of fist source!-&grave;analyte auto antibody!-&grave;antigenic molecule of second source! The antigenic molecule of first source is immobilized to a solid phase, the second is labeled.

This invention relates to a crystallisable composition comprising a TSHR polypeptide, to crystals comparing a TSHR polypeptide and to TSHR-related applications.

Crystal structure

According to one aspect there is provided an isolated human antibody molecule which binds to the TSHR and which reduces ligand-induced stimulation of the TSHR but has no effect on TSHR constitutive activity, wherein the isolated human antibody molecule has the characteristic of patient serum TSHR autoantibodies of inhibiting TSH and M22 binding to the TSHR.

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) the stimulatory effect of TSH when interacting with the mutated TSHR preparation is essentially unaffected, when compared to the stimulatory effect of TSH interacting with said reference TSHR preparation, and (iii) the blocking effect of patient serum blocking TSHR autoantibodies interacting with the mutated TSHR preparation is essentially unaffected or increased, when compared to the blocking effect of the patient serum blocking TSHR autoantibodies interacting with said reference TSHR preparation, whereby said mutated TSHR preparation is effective in the differential screening and identification of patient serum stimulating TSHR autoantibodies, patient serum blocking TSHR autoantibodies and TSH in a sample of body fluid being screened.

Mutated thyrotropin receptor

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.

Binding partners for the thyrotropin receptor and uses thereof

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.

Human monoclonal antibodies to the thyrotropin receptor which act as antagonists

The present invention is concerned with epitope regions of thyrotrophin (TSH) receptor, uses thereof and antibodies thereto.

Growing community of inventors

Cardiff, United Kingdom

Jadwiga Furmaniak