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Fusion protein for treating diabetes and preparation method for fusion protein

A fusion protein and diabetes technology, applied in the field of diabetes treatment drugs, can solve the problems of adverse reactions, large effective doses, and high production costs, and achieve the effects of prolonging the half-life of drugs, reducing the number of administrations, and avoiding adverse reactions.

Inactive Publication Date: 2012-07-11
DONGGUAN JINLANG BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

When used as a drug fusion mode to increase the half-life, the ADCC effect and CDC effect in the biological effects of IgG Fc fragments are useless, even harmful, and often cause adverse reactions
In addition, in the prior art, the fusion of GLP-1 receptor agonist GLP-1 or Exendin-4 with IgG uses a target peptide segment to be fused with IgG, its specific activity is relatively low, the effective dose is too large, and it is easy to cause adverse reactions. Increased reaction risk and higher production costs

Method used

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  • Fusion protein for treating diabetes and preparation method for fusion protein
  • Fusion protein for treating diabetes and preparation method for fusion protein
  • Fusion protein for treating diabetes and preparation method for fusion protein

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0082] like figure 2 As shown, in this example, the fusion protein used to treat diabetes is a fusion protein composed of two Exendin-4-Linkers and human IgG Fc mutants; the Linker flexible peptide is (Gly 4 Ser) n, n=1-5; human IgG Fc mutant is IgG1 Fc mutant, and the amino acid mutation position of IgG1 Fc mutant is Glu233Pro / Leu234Val / Leu235Ala / ΔGly236; combined mutation position of Ala327Gly / Ala330Ser / Pro331Ser, wherein Mutation positions are numbered according to the EU index.

[0083] Among them, the Linker connected to Exendin-4 at both ends is a flexible peptide segment (Gly 4 Ser) n, n=3;

[0084] Among them, the Linker whose one end is connected to Exendin-4 and the other end is connected to the human IgG1 Fc Fc mutant is a flexible peptide (Gly 4 Ser) n, n=1.

Embodiment 2

[0086] like figure 2 As shown, in this example, the fusion protein used to treat diabetes is a fusion protein composed of two Exendin-4-Linkers and human IgG Fc mutants; the Linker flexible peptide is (Gly 4 Ser) n, n=1-5; the human IgG Fc mutant is an IgG1 mutant, and the amino acid mutation position of the IgG1 Fc mutant is Glu233Pro / Leu234Val / Leu235Ala / ΔGly236; the combined mutation position of Ala327Gly / Ala330Ser / Pro331Ser, wherein the mutation Position numbers are according to the EU index.

[0087]Among them, the Linker connected to Exendin-4 at both ends is a flexible peptide segment (Gly 4 Ser) n, n=4;

[0088] Among them, the Linker whose one end is connected to Exendin-4 and the other end is connected to the human IgG1 Fc mutant is a flexible peptide (Gly 4 Ser) n, n=2.

Embodiment 3

[0090] like figure 2 As shown, in this example, the fusion protein used to treat diabetes is a fusion protein composed of two Exendin-4-Linkers and human IgG Fc mutants; the Linker flexible peptide is (Gly4Ser)n, n=1-5; Human IgG Fc mutants are IgG1 mutants, and the amino acid mutation positions of IgG1 Fc mutants are the combined mutation positions of Glu233Pro / Leu234Val / Leu235Ala / ΔGly236; Ala327Gly / Ala330Ser / Pro331Ser, wherein the mutation positions are numbered according to the EU index.

[0091] Among them, the Linker connected to Exendin-4 at both ends is a flexible peptide segment (Gly 4 Ser) n, n=3;

[0092] Among them, the Linker whose one end is connected to Exendin-4 and the other end is connected to the human IgG1 Fc mutant is a flexible peptide (Gly 4 Ser) n, n=3.

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Abstract

The invention relates to the technical field of medicines for treating diabetes, in particular to a fusion protein for treating diabetes and a preparation method for the fusion protein. The fusion protein is recombined by 2 to 8 Exendin-4-Linkers and a human IgGFc mutant; Linker is a flexible peptide fragment; and the human IgGFc mutant is an IgG1Fc, IgG2Fc or IgG4Fc mutant. The invention also discloses the preparation method for the fusion protein. The recombined fusion protein obtained by the steps of performing high-level expression in Chinese hamster ovary (CHO) cells, affiliating, and performing ion exchange and molecular sieve chromatography has the bioactivities of stimulating the secretion of insulin and inhibiting glucagon generated after dinner from being released which are possessed by Exendin-4, also has the characteristics of prolonging the half-life period of the Exendin-4 in serum, is used for treating type I and type II diabetes, can effectively reduce the psychological and physiological burden of patients, is safe in use and high in practicability, and can be massively produced and sold.

Description

technical field [0001] The invention relates to the technical field of drugs for treating diabetes, in particular to a fusion protein for treating diabetes and a preparation method thereof. Background technique [0002] Diabetes is a serious metabolic disorder of its own, which can cause serious cardiovascular dysfunction and has the characteristics of high morbidity and mortality, which seriously endangers human health and quality of life, and causes a heavy economic burden to patients and society. . According to epidemiological survey statistics, the total number of diabetic patients in the world has exceeded 120 million, of which about 90% are type 2 diabetes, and this number will continue to rise. It is estimated that by 2025, 300 million people worldwide will suffer from diabetes. Therefore, the development of specific diabetes drugs has high social benefits and market prospects. [0003] At present, type 1 diabetes is mainly treated by injecting insulin, while the tr...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00C07K1/22C07K1/18C07K1/16C12P21/02A61K38/22A61K47/48A61P3/10
Inventor 沈虹
Owner DONGGUAN JINLANG BIOTECH
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