LAG-3 Binding Members in CH3 Domain for Cancer Therapy
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current anti-LAG-3 therapies for cancer treatment are limited, with few options in clinical testing and none approved for therapy, highlighting a need for additional molecules that can effectively target LAG-3 in cancer therapy.
Innovation Solution
Development of specific binding members, such as antibody molecules or fragments, with high affinity for LAG-3, specifically designed to bind to the CH3 domain, which include antigen-binding sites in structural loops, to inhibit LAG-3 activity and enhance T cell activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional anti-LAG-3 therapies are used, then immune suppression is targeted, but the number of available therapeutic options is limited
Solution Approach 1:
The patent segments the antibody molecule into distinct functional domains, specifically placing the LAG-3 antigen-binding site within the CH3 domain rather than the conventional variable region. This segmentation creates novel binding members with unique structural characteristics that expand the repertoire of available LAG-3 targeted therapies
Solution Approach 2:
The invention moves the antigen-binding site from the traditional N-terminal variable region to the C-terminal CH3 domain, representing a dimensional shift in antibody architecture. This repositioning creates new therapeutic modalities with potentially different pharmacokinetic and pharmacodynamic properties, thereby increasing adaptability of treatment options
2Reliability
If LAG-3 binding members are designed with antigen-binding sites in CH3 domain structural loops, then high affinity binding is achieved, but structural complexity increases
Solution Approach 1:
The patent applies local quality by concentrating the antigen-binding functionality specifically within the structural loops of the CH3 domain, while the rest of the antibody structure maintains conventional configuration. This localized functional assignment achieves high binding affinity through optimized local interactions without requiring global structural complexity
Solution Approach 2:
The CH3 domain, traditionally serving as a constant region involved in effector functions, is赋予 dual functionality by incorporating LAG-3 binding capability. This multi-functionality reduces the need for separate variable region elements, potentially simplifying overall molecular design while achieving high affinity binding
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These specific binding members demonstrate high affinity and activity in T cell activation assays, showing potential for improved efficacy in reducing tumour growth by overcoming LAG-3-mediated immune suppression and reactivating anti-tumour responses.
Implementation Method 1
specific binding members which bind to lymphocyte-activation gene 3 (LAG-3)... comprise a LAG-3 antigen-binding site
Data Source
Figure 1A
Figure 1B
Figure 2
AI summary
The present invention relates to specific binding members which bind to lymphocyte- activation gene 3 (LAG-3). The specific binding members preferably comprise a LAG-3 antigen-binding site which may be located in two or more structural loops of a CH3 domain of the specific binding member. The specific binding members of the invention find application, for example, in cancer therapy.