Human monoclonal antibodies to the thyrotropin receptor which act as antagonists

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

Active Publication Date: 2010-02-24
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] The antibody and TSH preparations are diluted in cyclic AMP assay buffer.

[0206] Table 2c

[0207] The effect of 5C9 IgG and 9D33 IgG on the stimulation of cyclic AMP produced by TSH or M22Fab in CHO cells expressing human TSHR

[0208]

Test sample

Cyclic AMP production

(fmol / cell well; mean±SD n=3)

Only cyclic AMP assay buffer

473±21

PTSH only 3ng / mL

12,270±980

Only 5C9 IgG 100μg / mL

426±27

Only 5C9 IgG 10μg / mL

360±53

Only 5C9 IgG 1μg / mL

376±18

Only 5C9 IgG 0.1μ / mL

404±42

Only 5C9 IgG 0.01μg / mL

578±65

Only 5C9 IgG 0.001μg / mL

554±47

5C9IgG 100μg / mL+pTSH 3ng / mL

1094±70

5C9 IgG 10μg / mL+pTSH 3ng / mL

1028±47

5C9 IgG 1μg / mL+pTSH 3ng / mL

1872±168

5C9 IgG 0.1μg / mL+pTSH 3ng / mL

3920±464

5C9 IgG 0.01μg / mL+pTSH 3ng / mL

15,050±386

5C9 IgG 0.001μg / mL+pTSH 3ng / mL

14,147±1,310

9D33 IgG only 100μg / mL

626±127

9D33 IgG 100μ...

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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 that react with thyroid-stimulating hormone (TSH) receptors (TSHR), and specifically, but not exclusively, to antibodies that can bind to TSHR and can pass through TSH-stimulating antibodies or TSHR-stimulating antibodies block TSHR activation. 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 consisting of three domains: a leucine-rich domain (LRD), a cleavage domain (CD), and a 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 modelling. Thyroid 14: 9...

Claims

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Application Information

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Patent Type & Authority Applications(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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