Long-acting insulin or insulin analogue complex

一种胰岛素类似物、胰岛素的技术,应用在非凡的胰岛素和/或胰岛素类似物缀合物以及制备其领域,能够解决不具有半衰期、患者不便等问题,达到增加半衰期的效果

Inactive Publication Date: 2018-03-16
HANMI PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these long-acting insulin preparations do not have sufficient half-life and thus should be administered once or twice a day, causing inconvenience to the patient

Method used

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  • Long-acting insulin or insulin analogue complex
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  • Long-acting insulin or insulin analogue complex

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0140] Example 1: Synthesis of the gene for the A-chain and B-chain linker of native insulin

[0141] The immunoglobulin Fc region was fused to each of the A-chain and B-chain of native insulin separately at the gene level and inserted into an expression vector.

[0142] Specifically, linking substances were synthesized in which each of the following A-chain and B-chain of native insulin was included (Table 1). Specifically, an immunoglobulin Fc region in which serine—the 24th amino acid of the CH3 region—is substituted with histidine and in which phenylalanine—the 75th amino acid of the CH3 region—is substituted with alanine is synthesized The immunoglobulin Fc region that is conjugated to the A-chain. In addition, an immunoglobulin domain in which tyrosine - the 9th amino acid of the CH3 domain - is substituted with threonine and in which threonine - the 54th amino acid of the CH3 domain - is substituted with phenylalanine is synthesized The immunoglobulin Fc region that ...

Embodiment 2

[0147] Example 2: Preparation of natural insulin-linked substances showing polycistronic expression

[0148]After the synthesis of Example 1, the DNA fragment of the B-chain-IgG1Fc-linked substance was inserted into the vector having the A-chain-IgG1Fc-linked substance using restriction enzymes, so that the A-chain-IgG1Fc-linked substance and B The -chain-IgG1Fc-linking substance, the A-chain-IgG1Fc-linking substance and the B-chain-IgG1Fc-linking substance were inserted into each of the expression vectors. In order to construct a polycistronic expression system, an expression vector was constructed so that the genes of the above two linking substances were inserted into the pET22b vector—the expression vector. Instead of splitting the A-chain-IgG1Fc linker material in the vector where the A-chain-IgG1Fc is inserted, the SalI and XhoI restriction sites - which are present in the multiple cloning site - are split and then the B-chain-IgG1Fc A DNA segment of the ligated subst...

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PUM

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Abstract

The present invention relates to an insulin and / or insulin analogue complex and a use thereof, the insulin and / or insulin analogue complex having improved in-vivo persistence and stability by connecting the insulin and / or insulin analogue with the Fc region of immunoglobulin. The insulin and / or insulin analogue complex according to the present invention is a groundbreaking insulin and / or insulin analogue complex which is a long-acting formulation of insulin and / or insulin analogue showing activities similar to insulin in the body and having a remarkedly increased half-life in the blood, and which does not induce hypoglycemia which is a demerit of insulin treatment.

Description

[technical field] [0001] The present invention relates to insulin and / or insulin analogue conjugates and uses thereof, said insulin and / or insulin analogue conjugates having improved in vivo duration and stability - due to insulin and / or analogues thereof and the ability to Covalent linkage between biocompatible substances that increase half-life in vivo. More specifically, the present invention relates to extraordinary insulin and / or insulin analogue conjugates in which side effects caused by insulin therapy are reduced, and methods for their preparation, At the same time dosing compliance is improved - because of the in vivo persistence properties present therein. Furthermore, the present invention provides conjugates wherein insulin and / or insulin analogues and a biocompatible substance capable of increasing half-life in vivo are linked by a covalent bond. [Background technique] [0002] Insulin is a hormone secreted by the body's pancreas that regulates blood sugar lev...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00A61K38/28A61K47/68A61P3/10
CPCC07K14/62A61K38/00C07K2319/30A61K38/28A61K47/50A61P3/10A61K47/6811A61K47/60C07K2317/52C07K2317/522C07K2317/524C07K2317/526C07K2317/528C07K2317/53C12N15/67C12N2840/203
Inventor 许容豪李钟守朴晟喜金大桭郑圣烨权世昌
Owner HANMI PHARMA
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