Anti-PD-L1 Antibody Variable Region Optimization
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Solution Overview
Problem
Current PD-1/PD-L1 inhibitors, such as Opdivo, show limited efficacy due to low PD-L1 expression in tumors, necessitating the development of a novel anti-PD-L1 antibody with improved binding ability and function to enhance immune activation against cancer cells.
Innovation Solution
A novel anti-PD-L1 antibody with optimized heavy-chain and light-chain variable regions, including specific CDR sequences, is developed to enhance binding affinity and immune activation, comprising a heavy-chain variable region with CDR1, CDR2, and CDR3 sequences and a light-chain variable region with CDR1, CDR2, and CDR3 sequences, encoded by nucleic acids and produced using a vector in transformed cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-PD-L1 antibodies (e.g., Opdivo, Keytruda) are used, then PD-1/PD-L1 signaling is inhibited, but tumor suppression efficacy is limited due to low PD-L1 expression in tumors
Solution Approach 1:
The patent modifies the antibody structure by changing parameters of the variable regions, specifically optimizing heavy-chain CDR1, CDR2, and CDR3 sequences along with light-chain CDR sequences. This structural parameter change enables the antibody to bind with higher affinity to PD-L1, thereby improving both signal inhibition efficacy and tumor suppression despite low PD-L1 expression levels in tumors.
Solution Approach 2:
The patent focuses on optimizing specific local regions of the antibody molecule - the complementarity-determining regions (CDRs) in both heavy and light chains. By improving the local quality of these critical binding regions, the antibody achieves enhanced PD-L1 binding affinity and functional efficacy without requiring changes to the entire antibody structure.
2Productivity
If PD-L1 expression level in tumor is low, then fewer patients respond to therapy, but increasing PD-L1 expression would require changing tumor biology which is not controllable
Solution Approach 1:
The patent changes the binding parameters of the anti-PD-L1 antibody by optimizing the variable region sequences. This allows the antibody to detect and bind to PD-L1 at lower expression levels, thereby expanding the pool of responding patients to include those with low PD-L1 expression tumors who would not respond to conventional antibodies.
Solution Approach 2:
The patent replaces the conventional antibody binding mechanism with an optimized binding mechanism that has higher affinity and lower KD value. This substitution allows the antibody to effectively engage PD-L1 even when expressed at low levels, overcoming the limitation of conventional antibodies that require high PD-L1 expression for therapeutic response.
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
The optimized anti-PD-L1 antibody demonstrates increased PD-1/PD-L1 signal inhibition efficacy and improved tumor suppression in preclinical models, offering enhanced therapeutic potential for cancer treatment.
Implementation Method 1
an antibody binding to PD-L1 or an antigen-binding fragment thereof... increased PD-1/PD-L1 signal inhibition efficacy
Data Source
AI summary
Disclosed are an anti-PD-L1 antibody or an antigen-binding fragment thereof, a nucleic acid encoding the same, a vector including the nucleic acid, a cell transformed with the vector, a method for producing the antibody or an antigen-binding fragment thereof, a pharmaceutical composition for preventing or treating cancer containing the same, and a composition for co-administration with an antibody other than an antibody binding to PD-L1, containing the same.