A26 Fab'-PEG Antibody Hinge Modification for OX40 Binding
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Solution Overview
Problem
There is a need for an improved anti-OX40 antibody with high affinity for treating pathological disorders mediated by OX40 or associated with increased OX40 levels, as existing antibodies have limitations in efficacy and specificity.
Innovation Solution
A high affinity antagonistic anti-OX40 antibody, A26 Fab'-PEG, is developed, which comprises specific CDR sequences and a modified hinge region for enhanced binding and blocking capabilities, allowing for effective inhibition of OX40-OX40L interactions and T cell proliferation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-OX40 antibodies are used, then therapeutic effect is achieved, but affinity and efficacy are insufficient
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure specifically at the hinge region to enhance binding affinity. The modified hinge region introduces additional disulfide bonds and alters the structural conformation, which directly changes the physical-chemical parameters of the antibody-OX40 interaction, resulting in improved binding strength and therapeutic efficacy without requiring higher antibody concentrations
2Reliability
If antibody affinity for OX40 is increased, then blocking capability is improved, but specificity may be compromised
Solution Approach 1:
The patent applies local quality by making targeted modifications only at the hinge region of the antibody while keeping the antigen-binding CDR regions unchanged. This localized structural modification enhances overall binding affinity and blocking capability through improved structural stability, while the preserved CDR regions maintain the original specificity for human OX40, thus resolving the contradiction between enhanced blocking and maintained specificity
Data Source
Figure 1(a)~1(e)
Figure 1(f)~1(h)
Figure 1(i)~1(k)
AI summary
The invention relates to antibody molecules having specificity for antigenic determinants of human OX40, therapeutic uses of the antibody molecules and methods for producing said antibody molecules.