Human anti tshr antibodies
AssigneeRSR Limited
InventorsBernard Rees-Smith, Jane Sanders, Jadwiga Furmaniak
Life of this patent
Estimating the term…
Abstract
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.
Claims23
1-48. (canceled)
An isolated human monoclonal or recombinant antibody or fragment thereof that binds to the TSH receptor, wherein the antibody or fragment thereof reduces ligand-induced stimulation of the TSH receptor but has no effect on constitutive activity of the TSH receptor.
An isolated human monoclonal or recombinant antibody or fragment thereof that binds to the TSH receptor, wherein the antibody or fragment thereof reduces ligand-induced stimulation of the TSH receptor but has no effect on constitutive activity of the TSH receptor, wherein the antibody or fragment thereof, at 1 μg/ml, inhibits greater than 90% of 125I-TSH binding to TSHR.
An isolated human monoclonal or recombinant antibody or fragment thereof that binds to the TSH receptor, wherein the antibody or fragment thereof reduces ligand-induced stimulation of the TSH receptor but has no effect on constitutive activity of the TSH receptor, wherein the antibody or fragment thereof, at 1 μg/ml, inhibits greater than 90% of TSH-biotin binding to TSHR.
An isolated human monoclonal or recombinant antibody or fragment thereof that binds to the TSH receptor, wherein the antibody or fragment thereof reduces ligand-induced stimulation of the TSH receptor but has no effect on constitutive activity of the TSH receptor, wherein the antibody or fragment thereof, at 1 μg/ml, inhibits greater than 90% of M22 Fab peroxidase binding to TSHR.
An isolated human monoclonal or recombinant antibody or fragment thereof that binds to the TSH receptor, wherein the antibody or fragment thereof reduces ligand-induced stimulation of the TSH receptor but has no effect on constitutive activity of the TSH receptor, wherein the antibody or fragment thereof, at 1 μg/ml, inhibits greater than 90% of TSH-mediated cAMP stimulation in CHO cells expressing TSHR.
An isolated human monoclonal or recombinant antibody or fragment thereof that binds to the TSH receptor, wherein the antibody or fragment thereof reduces ligand-induced stimulation of the TSH receptor but has no effect on constitutive activity of the TSH receptor, wherein the antibody or fragment thereof, at 1 μg/ml, inhibits greater than 90% of 125I-TSH binding to TSHR, TSH-biotin binding to TSHR, M22 Fab peroxidase binding to TSHR, and TSH-mediated cAMP stimulation in CHO cells expressing TSHR.
An isolated nucleic acid encoding:
- a VH domain having an amino acid sequence selected from the group consisting of residues 1-119 of SEQ ID NO:41 and residues 1-138 of SEQ ID NO:51;
- a VL domain having an amino acid sequence of residues 1-130 of SEQ ID NO:69;
- or
- a CDR selected from the group consisting of SEQ ID NOs:
- 42, 43, 44, 52, 53, 54, 70, 71, and 72.
An isolated crystal comprising a Fab fragment, wherein the Fab fragment has atomic coordinates shown in FIG. 8.
An isolated human monoclonal or recombinant antibody or fragment thereof that binds to the TSH receptor and stimulates the TSH receptor, wherein the antibody or fragment thereof comprises:
- an antibody VL domain having an amino acid sequence selected from the group consisting of residues 1-109 of SEQ ID NO:23 and residues 1-129 of SEQ ID NO:33;
- an antibody VH domain having an amino acid sequence selected from the group consisting of residues 1-122 of SEQ ID NO:5 and residues 1-141 of SEQ ID NO:15;
- or
- a CDR selected from the group consisting of SEQ ID NOs:
- 6, 7, 8, 16, 17, 18, 24, 25, 26, 34, 35, and 36.
A diagnostic method for detecting analyte antibodies to the TSH receptor, wherein the method comprises:
- contacting a sample containing the analyte antibodies with a fragment of the TSH receptor, wherein the fragment comprises amino acids 22-260 of the TSH receptor (SEQ ID NO:75).
Dependencies are inferred from the claim text.