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A kind of human interleukin 10-fc fusion protein and its medical application

A technology of interleukin and fusion protein, which is applied in the field of human interleukin 10-Fc fusion protein and its medical application, and can solve the problem of prolonging human interleukin 10-Fc fusion protein and its medical application, product heterogeneity, and half-life Short and other problems, to overcome the troubles of production process and quality control, inhibit tumor growth, increase the effect of stability

Active Publication Date: 2021-10-08
BEIJING DONGFANG BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In order to solve the problems of the short half-life of human IL-10 in the prior art and the inhomogeneous products of human IL-10 after PEGylation, the present invention provides a combination of human IL-10 and immunoglobulin Fc The human interleukin 10-Fc fusion protein and its medical application that the fragments are fused together, retain the biological activity of IL-10, and greatly prolong the half-life of IL-10 in vivo

Method used

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  • A kind of human interleukin 10-fc fusion protein and its medical application
  • A kind of human interleukin 10-fc fusion protein and its medical application
  • A kind of human interleukin 10-fc fusion protein and its medical application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Embodiment 1 of the present invention provides a human interleukin 10-Fc fusion protein, which is formed by fusing human interleukin 10 with the Fc fragment of immunoglobulin IgG through a linker peptide; wherein, the Fc fragment is human IgG1 Fc part; the amino acid sequence of human interleukin 10 is shown in SEQ ID No:1; the amino acid sequence of Fc fragment is shown in SEQ ID No:2;

[0032] The general formula of the connecting peptide is [GlyGlyGlyGlySer] 6 , the amino acid sequence of the connecting peptide is shown in SEQ ID No:4.

[0033] Wherein, SEQ ID No: 1 (amino acid sequence of human interleukin 10);

[0034] SPGQGTQSENSCTHFPGNLPNMLRDLRDAFSRVKTFFQMKDQLDNLLLKESLLEDFKGYLGCQALSEMIQFYLEEVMPQAENQDPDIKAHVNSLGENLKTLRLRLRRCHHRFLPCENKSKAVEQVKNAFNKLQEKGIYKAMSEFDIFINYIEAYMTMKIRN.

[0035] SEQ ID No: 2 (amino acid sequence of Fc fragment);

[0036] DKTHTCPPCPAPELEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKAYACAVSNKALPAPIEKTIS...

Embodiment 2

[0041] Embodiment 2 of the present invention provides a human interleukin 10-Fc fusion protein, which is formed by fusing human interleukin 10 with the Fc fragment of immunoglobulin IgG through a linker peptide; wherein, the Fc fragment is human IgG1 Fc part; the amino acid sequence of human interleukin 10 is shown in SEQ ID No:1; the amino acid sequence of Fc fragment is shown in SEQ ID No:3;

[0042] The general formula of the connecting peptide is [GlyGlyGlyGlySer] 6 , the amino acid sequence of the connecting peptide is shown in SEQ ID No:4.

[0043] Wherein, the amino acid sequence provided by SEQ ID No:1 and SEQ ID No:4 is identical to that in Example 1;

[0044] SEQ ID No: 3 (amino acid sequence of Fc fragment);

[0045] EPKSCDKTHTCPPCPAPELEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKAYACAVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK。

[0046] The spe...

Embodiment 3

[0048] Embodiment 3 of the present invention provides a human interleukin 10-Fc fusion protein, which is formed by fusing human interleukin 10 with the Fc fragment of immunoglobulin IgG through a linker peptide; wherein, the Fc fragment is human IgG2 Fc part, the amino acid sequence of the Fc fragment is shown in SEQ ID No: 5; the amino acid sequence of human interleukin 10 is shown in SEQ ID No: 1;

[0049] The general formula of the connecting peptide is [GlyGlyGlyGlySer] 6 , the amino acid sequence of the connecting peptide is shown in SEQ ID No:4.

[0050] Wherein, the amino acid sequence provided by SEQ ID No:1 and SEQ ID No:4 is identical to that in Example 1;

[0051] SEQ ID No: 5 (amino acid sequence of Fc fragment);

[0052] ERKCCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDISVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK。

[0053] The s...

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Abstract

The present invention relates to the field of biomedicine, and specifically provides a human interleukin 10-Fc fusion protein, which is formed by fusing human interleukin 10 with an Fc fragment of immunoglobulin IgG through a connecting peptide; wherein, The Fc fragment is selected from one of human IgG1, IgG2 or IgG4; the amino acid sequence of the human interleukin 10 is shown in SEQ ID No:1. The present invention is formed by fusion of human IL-10 and human immunoglobulin Fc fragment through a specific connecting peptide, which prolongs the half-life of human IL-10 in vivo and increases its stability in vivo. In addition, the present invention provides The human interleukin 10-Fc fusion protein can be used for the treatment of immune diseases and cancer.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a human interleukin 10-Fc fusion protein and its medical application. Background technique [0002] The human interleukin 10 (IL-10) gene is located on 1q31-32, with a full length of 5.1 kb and 5 exons. The IL-10 gene is composed of 178 amino acids. Human and mouse IL-10 genes have 75% of the same amino acid sequence. Human IL-10 is a 35KD dimer composed of two monomers through non-covalent There are two disulfide bonds in the monomer to maintain its structure and biological activity. It is currently known that all lymphocytes can synthesize IL-10, and the most important sources in the body are mainly mononuclear macrophages and T helper cells. In addition, dendritic cells, B cells, NK cells, cytotoxic T cells, hypertrophic cells Cells as well as neutrophils and eosinophils also synthesize the IL-10 gene. [0003] Over the years, people's understanding of IL-10 has mainly ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00A61K38/20A61K47/68A61P35/00A61P37/00
CPCC07K14/5428A61P35/00A61P37/00C07K2319/30A61K38/00A61K38/20A61K47/68C07K19/00C07K14/54C07K16/00
Inventor 白义张稳周建华
Owner BEIJING DONGFANG BIOTECH
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