Humanized targeted complement inhibitor protein double-mutant mCR2-mDAF and application thereof

A technology of inhibitors and complement receptors, applied in the field of fusion proteins, can solve problems such as slow process, and achieve the effects of improved inhibition efficiency, excellent anti-adhesion, and good ligand binding ability
CN110330561AActive Publication Date: 2019-10-15BEIJING COMPLEMENT THERAPEUTICS LTD
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Patent Information

Authority / Receiving Office
CN · China
Current Assignee / Owner
BEIJING COMPLEMENT THERAPEUTICS LTD
Publication Date
2019-10-15

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Abstract

The invention discloses a complement inhibitor DAF mutant, a fusion protein thereof with a complement receptor 2 mutant and use of the fusion protein in preparation of medicines treating autoimmune diseases. The DAF mutant is a molecular modification obtained by computer modeling and amino acid substitution. The fusion protein of the DAF mutant and the complement receptor 2 mutant has higher ligand binding and dissociation rates than wild-sequence fusion protein thereof, and has better ligand binding force. Biological distribution experiments prove that the fusion protein can rapidly aggregatein the arthritis position after entering a rheumatoid arthritis mouse model, and has a significant anti-adhesion / anti-inflammatory targeted inhibitory effect. In treatment for MRL / lpr lupus erythematosus mice, the fusion protein can significantly increase the survival rate of the mice, and symptoms such as proteinuria, glomerular score, interstitial inflammation, vasculitis and crescent / necrosisin the mice in the treatment group are significantly improved.
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Description

technical field

[0001] The invention discloses a fusion protein and belongs to the technical field of polypeptides. Background technique

[0002] The complement system is composed of more than 30 kinds of soluble protein molecules and is a part of the natural immune system. Its components include more than 30 kinds of molecules such as complement intrinsic components, various regulatory factors and complement receptors. The complement system can be activated through three relatively independent and interrelated pathways, thereby exerting various biological effects such as opsonizing phagocytosis, lysing cells, mediating inflammation, immune regulation, and clearing immune complexes. Cell or tissue destruction can also be caused indirectly by complement activation and its deposition on target structures. Complement activation products that mediate tissue damage are produced at various points in the complement pathway. Inappropriate complement activation on host tissues play...

Claims

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