Hyperglycosylated human growth hormone fusion protein and preparation method and application thereof

A technology of human growth hormone and fusion protein, which is applied in the field of hyperglycosylated human growth hormone fusion protein and its preparation, can solve the problems of short half-life and poor biological activity, and achieve improved biological activity, improved tolerance, and increased space effect of distance

Inactive Publication Date: 2016-12-28
AMPSOURCE BIOPHARMA (SHANGHAI) INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] In order to solve the problems of short serum half-life and poor biological activity of recombinant hGH, the present invention designs and prepares a highly glycosylated long-acting hGH fusion protein

Method used

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  • Hyperglycosylated human growth hormone fusion protein and preparation method and application thereof
  • Hyperglycosylated human growth hormone fusion protein and preparation method and application thereof
  • Hyperglycosylated human growth hormone fusion protein and preparation method and application thereof

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Embodiment Construction

[0045] IgG Fc variant

[0046] non-lytic Fc variant

[0047] The Fc element is derived from the Fc fragment of the constant region of immunoglobulin IgG, which plays an important role in the immune defense to eliminate pathogens. The effector function of Fc-mediated IgG exerts two mechanisms: (1) Binding to cell surface Fc receptors (FcγRs), digesting pathogens by phagocytosis or lysis or killing cells through the antibody-dependent cellular cytotoxicity (ADCC) pathway , or (2) binding to C1q of the first complement component C1, triggering the complement-dependent cytotoxicity (CDC) pathway, thereby lysing the pathogen. For therapeutic application in humans, when the hGH-L-CTP-vFc fusion protein binds to hGH receptors on the surface of target cells, the Fc region of the fusion protein preferably does not have adverse effector functions and thus does not dissolve Or remove these target cells. Therefore, the Fc region of hGH-Fc must be insoluble, preferably inactive for bind...

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Abstract

The invention discloses hyperglycosylated human growth hormone fusion protein. The human growth hormone fusion protein sequentially contains a human growth hormone (hGH), a flexible peptide joint (L), human chorionic gonadotropin beta-carboxyl terminal rigid peptide (CTP) and a human immunoglobulin Fc fragment from the N terminal to the C terminal. The invention further discloses a method for efficiently preparing the fusion protein. Compared with a recombinant hGH, the built fusion protein has more excellent in-vivo drug efficacy, the in-vivo circulation half-life period is prolonged, the administration frequency is greatly decreased, and the bioavailability is improved; meanwhile, the production process is simpler and more efficient.

Description

technical field [0001] The invention relates to the field of fusion proteins, more specifically, the invention relates to a hyperglycosylated human growth hormone fusion protein and its preparation method and application. Background technique [0002] Human growth hormone (hGH) is a protein hormone secreted by eosinophilic cells in the anterior pituitary gland. It consists of 191 amino acids. Its physiological function is mainly to promote material metabolism and growth and development. hGH acts on cartilage tissue through growth-promoting factors or insulin-like growth factors to increase bone length, thereby promoting the linear growth of the human body. In recent years, more functions of hGH have been discovered, including promoting the growth of skeletal muscle and cardiomyocytes, promoting protein synthesis, regulating immune system function and enhancing immune defense. The large-scale clinical application of hGH has also expanded from the initial prevention and treat...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00C12N15/62A61K38/27A61K47/48A61P5/00
CPCA61K38/00C07K14/59C07K14/61C07K2319/30C07K2319/31A61K38/27A61P5/00C07K19/00C12N15/62
Inventor 李强陈思郑云程马心鲁李子瑞
Owner AMPSOURCE BIOPHARMA (SHANGHAI) INC
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