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Immunomodulatory fusion proteins

A technology of fusion protein and immunoglobulin, applied in the fields of cytokine receptor fusion protein, immunology and fusion protein, which can solve problems such as existing demand

Pending Publication Date: 2020-08-07
EPICENTRX
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Despite the progress made to date in the treatment of IL-10-mediated disorders, there remains a need for improved therapies for these disorders

Method used

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Examples

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Embodiment 1

[0110] Embodiment 1: IL-10RA fusion protein particle construction

[0111] This example describes the generation of plasmid and viral expression vectors encoding IL-10RA fusion proteins.

[0112] Nucleotide sequences encoding a series of human IL-10RA fusion proteins were generated. The first fusion protein hIL-10R-IgG1 (SEQ ID NO: 58) includes nucleotide residues 1-229 of human IL-10RA (ending at SLTRQ), followed by nucleotide residues 84-330 of the human IgG1 sequence. residues (starting with NVNHK). The second fusion protein hIL-10R-Fc (SEQ ID NO: 48) includes residues 1-235 of human IL-10RA (ending at FTVTN), followed by residues 104-324 of human IgG1 (ending at at DKTHT). Details of the fusion proteins are shown in Table 3.

[0113] table 3

[0114]

[0115] The nucleotide sequence encoding the fusion protein is optionally cloned into a plasmid for downstream applications. Specifically, recombinant adenoviral vectors expressing hIL-10R-IgG1 or hIL-10RA-Fc without...

Embodiment 2

[0116] Embodiment 2: IL-10R fusion protein activity

[0117] A549 cells (human lung cancer cells) were infected with the virus vectors described in Example 1 not expressing the transgene but expressing hIL-10R-IgG1 or hIL-10RA-Fc at 10 MOI and cultured for four days. Collect the modulated medium from the cell culture, and THP-1 cells (human leukemia mononuclear cells) are divided into 5×10 6 cells / ml were suspended in the conditioned medium. Cells were treated with 50 ng / ml human IL-10 for 30 minutes at 37°C, or left as is as a control. To measure IL-10 activity, extracted intracellular proteins from THP-1 cells were probed for phosphorylated Stat3 by Western blot. Total Stat3 was used as an internal reference.

[0118] IL-10 induced Stat3 phosphorylation in THP-1 cells cultured in conditioned medium from cells infected with a viral vector not expressing the transgene or expressing hIL-10RA-Fc. However, IL-10 did not induce Stat3 phosphorylation in THP-1 cells cultured in ...

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Abstract

Provided is a fusion protein, e.g., a cytokine receptor fusion protein, e.g., an IL-10 trap, with a novel linker sequence to permit the fusion protein to functionally optimally, e.g., to permit a cytokine receptor portion of a cytokine receptor fusion protein to bind optimally to its target cytokine. The fusion protein, or an expression vector encoding for the fusion proteins, can be used to treatcell proliferative diseases and disorders, including certain forms of cancer and inflammatory disorders.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of and priority to U.S. Provisional Patent Application Serial No. 62 / 564,145, filed September 27, 2017, which is hereby incorporated by reference in its entirety. technical field [0003] The field of the invention is molecular biology, in particular immunology and fusion proteins, such as cytokine receptor fusion proteins. Background technique [0004] Cytokines are small, secreted cell signaling proteins that have a wide range of activities, including regulation of cell growth and differentiation and modulation of immune function. Cytokines, cytokine receptors and certain other immunomodulatory proteins have been used as therapeutic agents to treat a variety of different medical conditions. However, administration of these proteins, for example by subcutaneous or vascular routes, may cause inappropriate cellular and extracellular localization, thereby limiting therapeutic activity...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00C07K14/715A61K38/16A61P35/00
CPCC07K14/5428A61K38/2066C12N15/62C07K2319/30C07K2319/50A61P35/00A61P31/00A61P29/00A61K38/19A61K38/00C07K14/7155C07K2319/03
Inventor 克里斯托弗·拉森托尼·R·雷德布莱恩·T·奥兰斯基
Owner EPICENTRX