PDL-1 antibody, pharmaceutical composition thereof and application of PDL-1 antibody

A technology of antibody and monoclonal antibody, which is applied in the fields of tumor therapy and molecular immunology, and can solve problems such as decreased expression of T cell surface activation markers

Active Publication Date: 2017-09-12
SICHUAN KELUN BIOTECH BIOPHARMACEUTICAL CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Studies have shown that the PDL-1 / B7-1 complex is also a negative signal for T cell activation, and the combination of the two can lead to a decrease in the expression of T cell surface activation markers, inhibit T cell proliferation, etc.

Method used

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  • PDL-1 antibody, pharmaceutical composition thereof and application of PDL-1 antibody
  • PDL-1 antibody, pharmaceutical composition thereof and application of PDL-1 antibody
  • PDL-1 antibody, pharmaceutical composition thereof and application of PDL-1 antibody

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0178] Preparation Example 1: Preparation of Fusion Protein PDL-1ECD-mFc

[0179] 1. Synthesis of gene PDL-1ECD-mFc

[0180] For the extracellular fragment PDL-1ECD (programmed cell death 1ligand 1, NCBIGenBank ID: NP_054862.1) of the gene PDL-1, PDL-1 and PD-L1 can be used interchangeably in scientific literature, and PDL-1 is used uniformly in this paper. The corresponding amino acid sequence is fused with the Fc protein fragment (mFc) of mouse IgG. In order to improve the expression efficiency of the target gene in the 293f cell expression system, GenScript was commissioned to optimize the nucleic acid sequence corresponding to the protein sequence, and GenScript was commissioned to synthesize the corresponding fusion protein gene.

[0181] 2. Acquisition of pUC57simple-PDL-1ECD-mFc plasmid:

[0182] The synthetic PDL-1ECD-mFc fusion gene was cloned by GenScript into the pUC57simple (provided by GenScript) expression vector to obtain the pUC57simple-PDL-1ECD-mFc plasmid...

preparation example 2

[0187] Preparation Example 2: Preparation of Fusion Protein PD-1-hFc

[0188] 1. Synthesis of gene PD-1-hFc

[0189] The amino acid sequence corresponding to the extracellular fragment PD-1ECD (Programmed cell death protein 1, NCBIGenBank ID: NP_005009.2) of gene PD-1 was fusion designed with the Fc protein fragment (hFc) of human IgG. In order to improve the expression efficiency of the target gene in the 293f cell expression system, GenScript was commissioned to optimize the nucleic acid sequence corresponding to the protein sequence, and GenScript was commissioned to synthesize the corresponding fusion protein gene.

[0190] 2. Acquisition of pUC57simple-PD-1ECD-TEV-hFc plasmid

[0191] The PD-1ECD-TEV-hFc fusion gene synthesized by GenScript was cloned into the pUC57simple (provided by GenScript) expression vector to obtain the pUC57simple-PD-1ECD-TEV-hFc plasmid.

[0192] 3. Construction of pcDNA3.1-PD-1ECD-TEV-hFc recombinant plasmid

[0193] The plasmid pUC57simple...

preparation example 3

[0196] Preparation Example 3: Preparation of B7-1-hFc

[0197] 1. Synthesis of gene B7-1-hFc

[0198] The amino acid corresponding to the extracellular fragment B7-1ECD of gene B7-1 (Cluster of Differentiation 80 (also CD80and B7-1), NCBIGenBank ID: NP_005182.1) was fusion designed with the Fc protein fragment (hFc) of human IgG. In order to improve the expression efficiency of the target gene in the 293f cell expression system, GenScript was commissioned to optimize the nucleic acid sequence corresponding to the protein sequence, and GenScript was commissioned to synthesize the corresponding fusion protein gene.

[0199] 2. Acquisition of pUC57simple-B7-1ECD-hFc plasmid

[0200] The B7-1ECD-hFc fusion gene synthesized by GenScript was cloned into the pUC57simple (provided by GenScript) expression vector to obtain the pUC57simple-B7-1ECD-hFc plasmid.

[0201] 3. Construction of pcDNA3.1-B7-1ECD-hFc recombinant plasmid

[0202] The plasmid pUC57simple-B7-1ECD-hFc was diges...

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PUM

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Abstract

The invention belongs to the field of oncotherapy and molecular immunology, and relates to a PDL-1 antibody, a pharmaceutical composition thereof and application of the PDL-1 antibody, in particular to a monoclonal antibody of PDL-1 or an antigen binding fragment thereof. A variable region of the heavy chain of the monoclonal antibody comprises CDR of which the amino acid sequence is SEQ ID NO: 15-17; and a variable region of the light chain of the monoclonal antibody comprises CDR of which the amino acid sequence is SEQ ID NO: 18-20. The monoclonal antibody can be well combined to PDL-1 specifically, inhibition of PDL-1 to body immunity is relieved specifically, and T lymphocyte is activated.

Description

technical field [0001] The invention belongs to the fields of tumor treatment and molecular immunology, and relates to an anti-PDL-1 antibody, its pharmaceutical composition and its application. Specifically, the present invention relates to an anti-PDL-1 monoclonal antibody. Background technique [0002] PD-1 / PDL-1 signaling pathway plays an important role in regulating immune tolerance, microbial infection and tumor immune escape. The expression of PD-1 (programmed cell death 1, programmed cell death factor 1) is mainly in immune cells such as T cells, and the ligand of PD-1, PDL-1, is mainly highly expressed in many human tumor tissues. Immunohistochemical methods have been used in breast cancer, lung cancer, gastric cancer, intestinal cancer, esophageal cancer, ovarian cancer, cervical cancer, kidney cancer, bladder cancer, pancreatic cancer, glioma, melanoma and other human tumors. The expression of PDL-1 protein was detected in tissues, and the expression level of PD...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28C12N15/13C12N5/20G01N33/68G01N33/577G01N33/574A61K39/395A61P35/00A61P35/02A61P7/06C12R1/91
CPCC07K16/2827G01N33/57407G01N33/57411G01N33/57446G01N33/577G01N33/68A61P7/06A61P35/02A61P35/00A61K2039/505C07K2317/56C07K2317/565C07K2317/92A61K39/395C07K14/70532C07K2317/24C07K2317/33C07K2317/52C07K2317/76C07K2319/50C07K2319/30C12N5/16C07K2317/734C07K2317/732C07K2317/31A61K47/6803C07K16/2896C07K16/462C07K16/468C07K2317/51C07K2317/515
Inventor 李百勇薛彤彤夏瑜王忠民肖亮王利春王晶翼
Owner SICHUAN KELUN BIOTECH BIOPHARMACEUTICAL CO LTD
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