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Pharmaceutical composition for treatment of immunological disorders

An immunological disease and composition technology, applied in the living field of cells, can solve the problems of difficult to achieve curative effect, inability to effectively suppress immune response, and limited application.

Inactive Publication Date: 2007-04-04
MEDEXGEN INC (KR)
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] However, the above-mentioned compounds cause significant adverse reactions when used in the treatment of immune diseases, thus limiting their application
As described in PCT Publication No. WO1996 / 40246, it is difficult to achieve the expected therapeutic effect when the antibody is administered alone
Moreover, since autoimmune diseases or transplant rejection result from the activation of T lymphocytes, blocking B cell function as described in PCT Publication No. WO2002 / 22212 cannot effectively suppress the immune response

Method used

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  • Pharmaceutical composition for treatment of immunological disorders
  • Pharmaceutical composition for treatment of immunological disorders
  • Pharmaceutical composition for treatment of immunological disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0077] Embodiment 1: Preparation of the DNA construct according to the coding Ig fusion protein of the present invention

[0078] A. Preparation of a DNA construct encoding the simple fusion monomeric protein LAG3 / Fc

[0079] a. A DNA fragment encoding the soluble extracellular domain of LAG3

[0080] The DNA fragment encoding the soluble extracellular domain of LAG3 can be constructed by PCR, utilizing the sequence (nucleosides whose sequence ID number is 7) with an EcoRI restriction site and a coding leader sequence (1-22 amino acid sequence whose sequence ID number is 8) Acid sequence) primers (nucleotide sequence whose sequence ID number is 1); Nucleotide sequence) antisense primer (nucleotide sequence whose sequence ID number is 4). The template cDNA for this reaction was constructed by reverse transcription PCR (RT-PCR) of mRNA extracted from healthy adult monocytes (T lymphocytes).

[0081] After drawing blood from healthy adults, it was diluted 1:1 with RPMI-1640 (G...

Embodiment 2

[0100] Embodiment 2: Preparation of the DNA construct according to the coding Ig fusion protein of the present invention

[0101] Simple fusion dimer proteins of other proteins TNFR1, TNFR2, CD2 and CTLA4 and linking fusion dimer proteins were prepared according to the same procedure as in Example 1. Detailed steps are described in PCT Publication No. WO2003 / 010202, which was filed by the present inventors. Information on the DNA and amino acid sequences of the Ig fusion proteins of TNFR1, TNFR2, CD2 and CTLA4 is summarized in Table 2 below.

[0102] Serial ID number

Embodiment 3

[0103] Example 3: Expression and Purification of Simple / Linked Fusion Dimeric Protein LAG3 / Fc

[0104] For expression of the fusion protein in CHO-K1 cells (ATCC CCL-61, ovary, Chinese hamster, Cricetulus griseus), pBluescript KS II(+) plasmid DNA containing the LAG3-LAG3 / Fc fusion gene was purified from transformed E. coli Afterwards, the LAG3-LAG3 / Fc fragment generated by restriction cutting with EcoRI and XbaI was expressed in the animal expression vector pCR TM 3 (Invitrogen, USA) was inserted into the EcoRI / XbaI site of the plasmid to construct an animal cell expression vector. These were designated as plasmid pLAG3-TOP10', and were deposited with the Korean Culture Center for Microorganisms (KCCM, 361-221, Yurim B / D, Hongje-1-dong, Seodaemun-gu, SEOUL 120-091, Korea).

[0105] The plasmid pLAG33IgDNA containing the LAG3-LAG3 / Fc fusion gene as described above was mixed with Lipofectamin TM (Gibco BRL, USA) reagents were mixed for transfection. CHO-K1 cells were treate...

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Abstract

Disclosed is a pharmaceutical composition for treating immunological disorders by inhibiting the activation of T lymphocytes, comprising, as active ingredients, two or more selected from the group consisting of a substance capable of blocking binding of an MHC (Major Histocompatibility Complex) Class II molecule and a receptor thereof, a substance capable of blocking binding of a costimulatory molecule and a receptor thereof a substance capable of blocking binding of an adhesion molecule and a receptor thereof, and a substance capable of blocking binding of a cytokine and a receptor thereof.

Description

technical field [0001] The present invention relates to a pharmaceutical composition for treating immune diseases by inhibiting the activation of T lymphocytes, which comprises as active ingredients two or more substances selected from the group consisting of substances capable of blocking MHC (major tissue compatibility complex) substances that bind class II molecules to their receptors, substances that block the binding of co-stimulatory molecules to their receptors, substances that block the binding of adhesion molecules to their receptors, and substances that block cytokines from their receptors body-bound substances. Background technique [0002] The immune response is the process of protecting oneself from attack by foreign bodies such as various impurities, bacteria or viruses. The immune system is finely tuned so that it does not attack itself. However, in some cases, the immune response attacks itself and damages the body. Immune rejection of transplanted organs o...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61K38/00C07K14/705C07K14/715
CPCC07K14/70503C07K14/715A61K38/00C07K2319/30A61P1/04A61P17/00A61P19/02A61P21/04A61P25/00A61P27/02A61P29/00A61P37/00A61P37/02A61P37/06A61P43/00A61P5/14A61P7/00A61P7/06A61P3/10A47J37/049A22C17/006
Inventor 郑用勋赵勋埴朴洪圭李基完
Owner MEDEXGEN INC (KR)
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