Anti-CTLA4 Antibody CDR Engineering for Stronger T Cell Activation

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Solution Overview

Problem

Existing anti-CTLA4 antibodies, such as Ipilimumab, may have limitations in binding affinity and efficacy for modulating immune responses, particularly in treating cancers and infectious diseases.

Innovation Solution

Development of mouse, chimeric, or humanized monoclonal antibodies or their antigen-binding portions with specific VH and VL CDR sequences that exhibit high binding affinity and blocking activity to CTLA4, as well as enhanced T cell response promotion, compared to existing antibodies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing anti-CTLA4 antibodies (e.g., Ipilimumab) are used, then immune response modulation is achieved, but binding affinity and efficacy are limited

Engineering Contradiction:

Improvebinding affinityVSAvoidefficacy

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent applies parameter changes by developing multiple antibody variants (mouse, chimeric, humanized) with optimized amino acid sequences in the CDR regions. These sequence modifications directly alter the binding parameters to achieve higher affinity for CTLA4 while maintaining or improving therapeutic efficacy compared to Ipilimumab

Inventive Principle:

Principle #35Parameter changes

2Productivity

If CTLA4-CD80/CD86 interaction is blocked, then T cell response is enhanced, but tumor growth inhibition requires higher efficacy

Engineering Contradiction:

ImproveT cell response promotionVSAvoidblocking activity

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent employs preliminary action by designing antibodies with pre-optimized high affinity for CTLA4 that can effectively block the CTLA4-CD80/CD86 interaction before it occurs. The engineered antibodies are configured to outcompete endogenous CTLA4 for CD80/CD86 binding sites, ensuring robust T cell response enhancement and tumor growth inhibition

Inventive Principle:

Principle #10Preliminary action

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 new antibodies effectively enhance immune responses and inhibit tumor growth or infectious disease progression by blocking CTLA4-CD80/CD86 interaction, offering improved therapeutic outcomes.

Implementation Method 1

an isolated monoclonal antibody, for example, a mouse, human, chimeric or humanized monoclonal antibody, or an antigen-binding portion thereof, that binds to CTLA4

Methodology Applied

Scientific EffectAntibody-antigen binding:

Data Source

PatentUS12559565B2Antibodies binding CTLA4 and uses thereof

Publication Date: 2026.02.24 BIOSION INC

AI summary

An isolated monoclonal antibody that specifically binds human CTLA4, or the antigen-binding portion thereof. A nucleic acid molecule encoding the antibody or the antigen-binding portion thereof, an expression vector, a host cell and a method for expressing the antibody or the antigen-binding portion thereof are also provided. The present disclosure further provides an immunoconjugate, a bispecific molecule, a chimeric antigen receptor, an oncolytic virus and a pharmaceutical composition comprising the antibody or the antigen-binding portion thereof, as well as a treatment method using the anti-CTLA4 antibody or the antigen-binding portion thereof.