Fully Human Anti-TNF Antibodies Reducing Immunogenicity
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Solution Overview
Problem
Existing anti-TNF antibodies face challenges such as immunogenicity, low specificity, and pharmaceutical unsuitability, limiting their effectiveness and safety for in vivo therapeutic use in humans.
Innovation Solution
Development of isolated mammalian anti-TNF antibodies with specific heavy and light chains (SEQ ID NO:36 and SEQ ID NO:37) for intravenous infusion, administered at specific doses and schedules, either alone or in combination with other medications like methotrexate, sulfasalazine, or hydroxychloroquine.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-TNF antibodies are used for therapeutic treatment, then inflammation suppression and disease management are achieved, but immunogenicity and pharmaceutical unsuitability limit safety and effectiveness
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure from chimeric to fully human format, changing the amino acid sequence parameters to reduce immunogenicity while maintaining therapeutic effectiveness against TNF-alpha in ankylosing spondylitis treatment
2Reliability
If existing anti-TNF antibodies are administered, then some therapeutic benefit is achieved, but low specificity limits treatment precision and safety
Solution Approach 1:
The patent applies local quality by designing the antibody with specific humanized variable regions (VL and VH domains) that maintain high specificity for TNF-alpha binding while the constant regions provide optimized pharmaceutical properties, achieving both precision and safety
3Object-generated harmful factors
If chimeric monoclonal antibodies are used, then inflammation suppression is achieved, but immunogenicity and repeated administration issues arise
Solution Approach 1:
The patent applies copying by creating a fully human antibody version that replicates the therapeutic function of the chimeric antibody, using human amino acid sequences that mimic the effective binding properties while eliminating the non-human immunogenic components
Data Source
AI summary
The present invention relates to compositions and methods utilizing anti-TNF antibodies having a heavy chain (HC) comprising SEQ ID NO:36 and a light chain (LC) comprising SEQ ID NO:37 for use in the safe and effective treatment of active Ankylosing Spondylitis (AS).