Unlock instant, AI-driven research and patent intelligence for your innovation.

Bifunctional protein aiming at VEGF and TGF-beta and application of bifunctional protein

A bifunctional protein and TGF- technology, which is applied in the field of biomedicine, can solve the problems such as the news that the bifunctional protein drug has entered the clinical stage is not disclosed, and achieve the effect of improving the therapeutic effect and reducing the side effects.

Active Publication Date: 2021-11-26
BEIJING DONGFANG BIOTECH
View PDF8 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In China, bifunctional proteins targeting PD-L1 and TGF-β and bifunctional proteins targeting PD-1 and TGF-β developed by many companies have entered the clinical stage, but bifunctional proteins targeting VEGF and TGF-β have not yet been disclosed. The news that protein drugs have entered the clinical stage, so in order to meet the needs of more cancer patients, it is urgent to develop a bifunctional protein drug targeting VEGF and TGF-β

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Bifunctional protein aiming at VEGF and TGF-beta and application of bifunctional protein
  • Bifunctional protein aiming at VEGF and TGF-beta and application of bifunctional protein
  • Bifunctional protein aiming at VEGF and TGF-beta and application of bifunctional protein

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0053] Example 1 of the present invention constructs a bifunctional protein targeting VEGF and TGF-β, including anti-VEGF monoclonal antibody capable of specifically binding to VEGF antigen, connecting peptide linker and TGF-βRII extracellular domain polypeptide, anti-VEGF The monoclonal antibody is connected to the TGF-βRII extracellular domain polypeptide through the linker peptide. The anti-VEGF monoclonal antibody includes two heavy chains and two light chains, and the TGF-βRII extracellular domain polypeptide is connected to the C-terminal or N-terminal of the two heavy chains or the two light chains of the anti-VEGF monoclonal antibody through a linker connect.

Embodiment 2

[0055] On the basis of Example 1, Example 2 of the present invention further defines the anti-VEGF monoclonal antibody. The anti-VEGF monoclonal antibody defined here is a monoclonal antibody targeting VEGF, and the present invention is preferably a bevacizumab monoclonal antibody. Antibody, the amino acid sequence of its heavy chain is SEQ ID NO:1, the amino acid sequence of its light chain is SEQ ID NO:2; the amino acid sequence of TGF-βRII extracellular domain polypeptide is SEQ ID NO:3.

[0056] The general formula of the connecting peptide linker is (GGGGS)n; the n is 4.

[0057] The bispecific antibody is selected from any of the following:

[0058] Protein EB-1, which is composed of TGF-βRII extracellular domain polypeptide connected to the C-terminals of the two heavy chains of anti-VEGF monoclonal antibody through the connecting peptide linker, the amino acid sequence of the heavy chain of protein EB-1 is SEQ ID NO :4, the amino acid sequence of its light chain is SE...

Embodiment 3

[0078] Embodiment 3 of the present invention provides a nucleotide molecule encoding a bifunctional protein targeting VEGF and TGF-β.

[0079] The present invention also provides a recombinant DNA expression vector, which contains the above-mentioned nucleotide molecules.

[0080] The present invention also provides a host cell transfected with a recombinant DNA expression vector, and the host cell includes prokaryotic, yeast or mammalian cells.

[0081] The present invention also provides the application of the bifunctional protein targeting VEGF and TGF-β in the preparation of drugs for treating tumor diseases or fibrotic diseases;

[0082] The neoplastic disease is selected from colorectal cancer, non-small cell lung cancer, breast cancer, pancreatic cancer, kidney cancer, gastric cancer, liver cancer, ovarian cancer, melanoma or glioma;

[0083] Fibrotic diseases include liver fibrosis and pulmonary fibrosis.

[0084] The present invention also provides the application o...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to the field of biological medicines, and particularly provides a bifunctional protein aiming at VEGF and TGF-beta. The bifunctional protein comprises an anti-VEGF monoclonal antibody capable of being specifically combined with a VEGF antigen, a connecting peptide linker and TGF-beta RII extracellular domain polypeptide, and the anti-VEGF monoclonal antibody is connected with the TGF-beta RII extracellular domain polypeptide through the connecting peptide linker. The bifunctional protein aiming at VEGF and TGF-beta provided by the invention can target a tumor microenvironment with high expression of VEGF and reduce side effects of a TGF-beta inhibitor, and the bifunctional protein not only can be singly used, but also can be combined with existing immunotherapy drugs such as a PD-1 / PD-L1 inhibitor, and can effectively improve the therapeutic effect of tumor diseases.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a bifunctional protein targeting VEGF and TGF-β and its application. Background technique [0002] With the continuous development of biomedicine, the immunotherapy of anti-PD-1 / PD-L1 monoclonal antibody has made a major breakthrough in the field of cancer treatment, such as metastatic melanoma, bladder cancer and non-small cell lung cancer, including more than 15 All types of cancer have been more effectively treated. However, anti-PD-1 / PD-L1 monoclonal antibodies are only effective in 20-30% of cancer patients, and many patients will quickly develop drug resistance even if they initially respond to treatment. At the same time, accumulating evidence shows that many cancers can develop multiple strategies to evade treatment, thus requiring the development of novel immunotherapies against cancer. [0003] Studies have shown that the tumor microenvironment is a key factor in ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00C12N15/62A61K47/65A61K47/64A61K39/395A61K45/06A61P35/00A61P1/16A61P11/00
CPCC07K16/22C07K14/71A61K47/65A61K47/64A61K39/3955A61K45/06A61P35/00A61P1/16A61P11/00C07K2317/51C07K2317/515C07K2317/92A61K2039/505A61K2039/507A61K2300/00
Inventor 白义
Owner BEIJING DONGFANG BIOTECH