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Myostatin binding proteins

A myostatin, binding protein technology, applied in the direction of anti-growth factor immunoglobulin, immunoglobulin, anti-animal/human immunoglobulin, etc., can solve the needs that cannot meet the needs of wider interests, reduce treatment and other problems

Inactive Publication Date: 2012-01-18
GLAXO GRP LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Because of these limitations, the need for broader benefits has largely fallen short of the need for treatments for conditions associated with a reduction in any one or a combination of muscle mass, muscle strength, and muscle function

Method used

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  • Myostatin binding proteins
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Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0329] 1. Production of Recombinant Proteins

[0330] 1.1 Purification of mature dimerized myostatin

[0331] The HexaHisGB1Tev / (D76A) mouse myostatin polyprotein sequence (SEQ ID NO: 101 ) was expressed in the CHO secretion system. The GB1 tag (SEQ ID NO: 102) described in WO2006 / 127682 was found to enable higher levels of myostatin expression and proper folding of myostatin compared to constructs with Fc tags. The mouse polyprotein sequence (SEQ ID NO: 103) can be used to generate the mature myostatin sequence (SEQ ID NO: 104), since the human and mouse mature myostatin sequences are 100% identical. To reduce any possible degradation of myostatin, use "DVQR A The D76A mutation in the DSSD" region was used to engineer the mouse polyprotein sequence.

[0332] The expressed HexaHisGB1Tev / (D76A) mouse myostatin polyprotein (minus signal sequence). The Ni eluate was buffer exchanged into furin lysis buffer (50 mM HEPES, pH 7.5, 0.1 M NaCl, 0.1% Triton X-100, 1 mM CaCl 2...

Embodiment 9

[0519] These results in Example 9 indicate that 10B3 or its humanized antibody can be used to treat glucocorticoid-induced muscle atrophy. For example, prophylactic treatment of muscle wasting may be beneficial in patients treated with glucocorticoids.

[0520] 10. 10B3 Treatment Attenuates Muscle Atrophy in a Sciatic Nerve Trauma Model

[0521] Here we use a neural injury model to evaluate the efficacy of 10B3 in preventing disuse atrophy in mice.

[0522] C57BL mice were treated with mIgG2a control or 10B3 antibody. The right sciatic nerve in the mid-thigh region was exposed, left intact (sham group) or injured by pinching with a haemostatic forcep for 10 seconds (nerve crush group). Sciatic nerve pinch resulted in decreased extensor digitorum longus (EDL), tibialis anterior (TA), gastrocnemius, and soleus muscle mass compared to sham-operated controls. In the sham group, 10B3 treatment increased TA, EDL, gastrocnemius and quadriceps muscle mass compared to the IgG2a co...

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Abstract

Description of antigen binding proteins, such as antibodies, which bind to myostatin, polynucleotides encoding such antigen binding proteins, pharmaceutical compositions comprising said antigen binding proteins and methods of manufacture. Furthermore, description of the use of such antigen binding proteins in the treatment or prophylaxis of diseases associated with any one or a combination of decreased muscle mass, muscle strength and muscle function.

Description

field of invention [0001] The present invention relates to an antigen-binding protein such as an antibody that binds to myosatin, a polynucleotide encoding the antigen-binding protein, a pharmaceutical composition comprising the antigen-binding protein, and a preparation method. The present invention also relates to the use of said antigen binding protein in the treatment or prevention of diseases associated with any one or combination of decreased muscle mass, muscle strength and muscle function. Background of the invention [0002] Myostatin, also known as growth and differentiation factor (GDF-8), is a member of the transforming growth factor-β (TGF-β) superfamily and a negative regulator of muscle mass. Myostatin is highly conserved during evolution, and human, chicken, mouse and rat sequences are 100% identical in the mature C-terminal domain. Myostatin is synthesized as a precursor protein containing a signal sequence, a propeptide domain and a C-terminal domain. The...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/22A61K39/395A61P21/00
CPCC07K2317/24C07K2316/96C07K2317/71C07K2317/92C07K2317/565C07K2317/56C07K16/22A61K2039/505C07K2317/76A61P1/16A61P11/00A61P13/12A61P17/02A61P19/02A61P19/08A61P19/10A61P21/00A61P25/00A61P25/16A61P25/28A61P29/00A61P3/04A61P31/18A61P35/00A61P43/00A61P7/00A61P9/00A61P9/04A61P3/10A61K39/395C12N15/11
Inventor C·阿什曼A·比顿J·H·艾利斯B·韩I·柯比F·库尔A·路易斯K·M·林德利M·A·奥雷基亚Y·沈P·威尔逊T·S·徐H·张
Owner GLAXO GRP LTD
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