Dimeric immunofusion proteins, pharmaceutical compositions and uses

A fusion protein and dimer technology, applied in the direction of drug combination, fusion polypeptide, peptide/protein components, etc., to achieve the effect of reducing tissue damage, good therapeutic effect, and broad clinical application prospects

Active Publication Date: 2022-07-12
PHARCHOICE THERAPEUTICS INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] In summary, it is urgent to develop drugs that can remove intruders and inhibit the excessive production of cytokines in the body, and the inventors have not seen any reports of similar drugs

Method used

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  • Dimeric immunofusion proteins, pharmaceutical compositions and uses
  • Dimeric immunofusion proteins, pharmaceutical compositions and uses
  • Dimeric immunofusion proteins, pharmaceutical compositions and uses

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0075] Example 1. Construction, expression and characterization of soluble dimer immunofusion proteins

[0076] like figure 1 As shown, the soluble dimer immunofusion protein is a dimer with antibody Fc, and the construction and expression methods of the dimer immunofusion protein itself are routine experimental techniques in the field, which are briefly described as follows:

[0077] (1) Entrust a gene synthesizer (Suzhou Jinweizhi Company) to perform coding nucleotide codon optimization and whole gene synthesis for the amino acid sequence of the dimer immune fusion protein required in this example, and the optimized nucleotide sequence is directly loaded into the On the PCDNA3.4 vector, the amino acid sequences encoded by all vectors are described in Table 1.

[0078] (2) Entrust a protein manufacturer (Yiqiao Shenzhou Company) to express and purify a dimer immunofusion protein for this example. Using the literature Finck B K. Science, 265.; Mihara M et al.. Journal of Cl...

Embodiment 2 2

[0088] Example 2 Effect of dimer immunofusion protein on Staphylococcus aureus

[0089] Staphylococcus aureus expressing green fluorescent protein was collected from the Institute of Microbiology, Chinese Academy of Sciences, and the multiplicity of infection was 1:10. Peripheral blood samples were collected from healthy volunteers to isolate peripheral mononuclear cells (PBMCs, which were isolated using Biyuntian Lymphocyte Separation Kit). Freshly isolated cells were stabilized for 2 h in RPMI1640 medium containing 10% fetal bovine serum (37.5°C, 5% CO). 2 ).

[0090] Cultivate Staphylococcus aureus according to the experimental requirements, collect the bacteria by centrifugation at 10000g for 30 seconds in a tabletop centrifuge, and resuspend to 10 8 Bacterial density around CFU / ml. The bacterial suspension was taken for serial dilution plate counts to determine the exact bacterial density. After the PBMC cells were replaced by medium, 10 microliters of PBS resuspended...

Embodiment 3

[0098] Example 3 Effect of immunodimer on methicillin-resistant Staphylococcus aureus

[0099] BALB / c mice, SPF grade, female, 6-8 weeks old, weighing 18-20 g, international standard strain MRSA-252, purchased from American Tissue Culture Collection (ATCC). A mouse model was established, and 0.1 mL of washed bacterial solution (the concentration of bacterial solution was 1 × 10) was injected through the tail vein. 9 CFU / mL), mice in the blank group were injected with an equal volume of sterile normal saline through the tail vein. Then the mice were divided into a control group and a treatment group, with 10 mice in each group, the control group was given control IgG, and the treatment group was given a representative of the dimer immunofusion protein of the present invention at a dose of 10 mg / kg, intravenously Injection once a day, continuous observation for 10d. If the mice died or all the mice were sacrificed at the end of the experiment on the last day, the blood was imm...

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Abstract

The invention relates to the technical field of biomedical engineering, and provides compositions and methods related to soluble dimer immunofusion proteins. The dimeric immunofusion protein comprises dimerized first and second polypeptide chains. The general structural formula of the first polypeptide chain is Z1-Z2, and the general structural formula of the second polypeptide chain is Y1-Y2. wherein Z1 is (i) an extracellular domain of a first pattern recognition receptor or a functional variant or fragment thereof, or (ii) a functional variant or fragment thereof of a first co-receptor; Z2 is a dimerization domain or functional variants or fragments thereof. Y1 is (i) the extracellular domain of a second pattern recognition receptor or a functional variant or fragment thereof, or (ii) a second co-receptor or a functional variant or fragment thereof, and Y2 is the dimerization domain or functional variants or fragments thereof. The dimeric protein can be used to block the invasion of pathogens, limit the production and expansion of inflammatory mediators, and can be used for the prevention of inflammatory mediator-related diseases or the preparation of therapeutic products.

Description

technical field [0001] The present invention relates to the technical field of biomedical engineering, in particular to a dimer immunofusion protein, a pharmaceutical composition using it as an active component, and its medical use, especially the use for inflammatory mediator-related diseases. Background technique [0002] In animals, an inflammatory response occurs when cells or tissues are damaged by bacteria, trauma, toxins, physical or chemical factors (which may be collectively referred to as "inflammatory agents"). The pathophysiological features of inflammatory responses are modulated by the complex interplay of multiple pro- or anti-inflammatory stimuli or mediators synthesized and released by cells. Some of the known classes of pro-inflammatory, anti-inflammatory stimulators or mediators include cytokines, nitrous oxide, thromboxanes, cyranes, phospholipid-like platelet-activating factors, prostaglandins, kinesin, complement factors, coagulation factors , superant...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07K19/00A61K38/17A61K47/68A61P1/16A61P11/00A61P13/12A61P15/00A61P15/06A61P29/00A61P31/04A61P31/10A61P31/12A61P31/14A61P33/00A61P33/10A61P37/02
CPCC07K14/70596C07K14/7056A61K47/68A61K47/6813A61P29/00A61P31/04A61P31/12A61P33/00A61P31/10A61P31/14A61P33/10A61P11/00A61P1/16A61P15/00A61P15/06A61P37/02A61P13/12C07K2319/00C07K2319/30A61K38/00
Inventor 傅文燕丁敏胡适
Owner PHARCHOICE THERAPEUTICS INC
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