Humanized Anti-IL-6 Antibodies Reducing Immunogenicity
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Solution Overview
Problem
Current antibodies targeting IL-6 are immunogenic in humans, leading to immune responses and reduced therapeutic efficacy due to their non-human origins, limiting their repeated administration and therapeutic benefit.
Innovation Solution
Development of chimeric, humanized, or CDR-grafted anti-IL-6 antibodies that incorporate high-affinity antigen binding regions from the murine CLB-8 antibody, specifically neutralizing human IL-6 with reduced immunogenicity by combining murine CDRs with human framework regions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-human antibodies are used to target IL-6, then high affinity binding and neutralizing capability are achieved, but immunogenicity increases leading to immune responses and reduced therapeutic efficacy
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure from completely non-human to chimeric or humanized forms. This involves changing the origin of different antibody regions: keeping CDRs from murine antibodies (for affinity) while changing framework regions to human sequences (to reduce immunogenicity). The constant regions are also changed to human isotypes. This structural parameter change resolves the contradiction between maintaining high affinity and reducing immunogenicity.
Solution Approach 2:
The patent creates composite antibody structures by combining regions from different sources: murine CDRs (for antigen binding capability) with human framework regions and constant regions (for reduced immunogenicity). This composite approach allows the antibody to inherit the high affinity binding properties of murine antibodies while gaining the low immunogenicity characteristics of human antibodies, thereby resolving the technical contradiction.
2Duration of action of moving object
If murine monoclonal antibodies are used against IL-6, then high affinity binding is achieved, but repeated administration is limited due to immune responses
Solution Approach 1:
The patent changes the immunogenicity parameter of the antibody by humanizing it. By replacing murine framework regions with human sequences and using human constant regions, the antibody becomes less recognizable to the human immune system. This parameter change allows repeated administrations without triggering strong immune responses that would otherwise limit therapeutic duration, while maintaining the high affinity binding properties necessary for therapeutic efficacy.
Data Source
AI summary
The present invention relates to at least one novel chimeric, humanized or CDR-grafted anti-IL-6 antibodies derived from the murine CLB-8 antibody, including isolated nucleic acids that encode at least one such anti-IL-6 antibody, vectors, host cells, transgenic animals or plants, and methods of making and using thereof, including therapeutic compositions, methods and devices.