Human BDCA-2 Antibody Variable Region Engineering
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Solution Overview
Problem
Current anti-human BDCA-2 antibodies are ineffective in controlling the function of plasmacytoid dendritic cells (pDCs), which are abnormally activated in autoimmune diseases like systemic lupus erythematosus, leading to excessive interferon-alpha production.
Innovation Solution
Development of a novel anti-human BDCA-2 antibody with specific amino acid sequences in its heavy and light chain variable regions, which binds to the extracellular region of BDCA-2 on pDCs, inhibiting IFNα production and controlling pDC function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mouse monoclonal antibody AC144 is used to inhibit pDC activation, then IFNα production is suppressed, but the antibody shows insufficient efficacy in controlling pDC function in autoimmune diseases
Solution Approach 1:
The patent applies parameter changes by modifying the antibody's species origin from mouse to human, and by optimizing the amino acid sequences in the variable regions. This creates a fully human anti-BDCA-2 antibody with enhanced binding affinity and specificity, thereby improving the reliability of pDC function control while maintaining the inhibitory effect on IFNα production.
2Measurement precision
If existing anti-BDCA-2 antibodies are used, then some inhibition of pDC activation is achieved, but they fail to effectively bind to human BDCA-2 and control pDC function
Solution Approach 1:
The patent applies local quality by specifically optimizing the amino acid sequences in the variable regions (VH and VL) of the antibody. By focusing modifications on these local binding regions while maintaining the overall antibody structure, the invention achieves enhanced binding specificity to human BDCA-2's extracellular domain, which directly improves both measurement precision and functional reliability.
3Object-generated harmful factors
If mouse monoclonal antibodies are used against human BDCA-2, then crosslinking of BDCA-2 molecules occurs, but the therapeutic effectiveness is limited
Solution Approach 1:
The patent applies this principle by replacing the mouse monoclonal antibody (which has limited therapeutic utility despite being easier to produce) with a fully human antibody. The human antibody structure allows for better therapeutic compatibility and prolonged effectiveness, making it a superior disposable therapeutic agent that can be produced through standard recombinant DNA technology in human cell lines.
Data Source
AI summary
[Problem] Provided is an anti-human BDCA-2 antibody for preventing or treating an autoimmune disease by binding to a human BDCA-2 to control the function of a plasmacytoid dendritic cell through human BDCA-2.[Means for Solution] The present inventors have investigated anti-human BDCA-2 antibodies, and as a result, they have provided an anti-human BDCA-2 antibody comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 120 of SEQ ID NO: 2 and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 109 of SEQ ID NO: 4, a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 120 of SEQ ID NO: 6 and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 8, and a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 122 of SEQ ID NO: 10 and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 12.