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Human monoclonal antibodies to the thyrotropin receptor which act as antagonists

A technology of thyroid-stimulating hormone and antagonist, applied in the direction of anti-receptor/cell surface antigen/cell surface determinant immunoglobulin, antibody, anti-animal/human immunoglobulin, etc.

Active Publication Date: 2014-09-03
R S R
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This may be disadvantageous given the cost and complexity involved in the humanization process

Method used

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  • Human monoclonal antibodies to the thyrotropin receptor which act as antagonists
  • Human monoclonal antibodies to the thyrotropin receptor which act as antagonists
  • Human monoclonal antibodies to the thyrotropin receptor which act as antagonists

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0199] sample

Embodiment 2

4131±776

[0203] 1 Average of duplicate samples

[0204] 2G4 = control IgG (human MAb against thyroid peroxidase).

[0205] Antibody and TSH preparations were diluted in cyclic AMP assay buffer.

[0206] Table 2c

[0207] Effects of 5C9IgG and 9D33IgG on stimulation of cyclic AMP production by TSH or M22Fab in CHO cells expressing human TSHR

[0208]

test sample

Cyclic AMP production

(fmol / cell well; mean±SD n=3)

Cyclic AMP assay buffer only

473±21

pTSH only 3ng / mL

12,270±980

5C9 IgG only 100 μg / mL

426±27

5C9 IgG only 10 μg / mL

360±53

5C9 IgG only 1 μg / mL

376±18

5C9 IgG only 0.1 μg / mL

404±42

5C9IgG only 0.01μg / mL

578±65

5C9IgG only 0.001μg / mL

554±47

5C9IgG 100μg / mL+pTSH 3ng / mL

1094±70

5C9IgG 10μg / mL+pTSH 3ng / mL

1028±47

5C9IgG 1μg / mL+pTSH 3ng / mL

1872±168

5C9IgG 0.1μg / mL+pTSH 3ng / mL

...

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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.

Description

technical field [0001] The present invention relates to antibodies reactive with the thyroid-stimulating hormone (TSH) receptor (TSHR), and in particular, but not exclusively, to antibodies that bind to the TSHR and are activated by TSH-stimulatory antibodies or TSHR-stimulatory antibodies block activation of TSHR. Background technique [0002] Thyrotropin or thyroid stimulating hormone (TSH) is a pituitary hormone that regulates thyroid function through TSHR (Szkudlinski MW, Fremont V, Ronin C, Weintraub BD 2002 Thyroid-stimulating hormone and TSHR structure-function relationships. Physiological Reviews 82:473-502). TSHR is a G protein-coupled receptor composed of 3 domains: leucine-rich domain (LRD), cleavage domain (CD) and transmembrane domain (TMD) (Nunez Miguel R, Sanders J, Jeffreys J, Depraetere H, Evans M, Richards T, Blundell TL, Rees Smith B, Furmaniak J 2004 Analysis of the thyrotropin receptor-thyrotropin interaction by comparative modeling. Thyroid 14:991-101...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K16/28C12N5/24A61K39/395C12N5/28A61P5/08G01N33/564C12N15/13
Inventor B·瑞斯史密斯J·福尔曼克J·桑德斯
Owner R S R
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