Anti-CTLA-4 Antibodies Selective Binding

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Solution Overview

Problem

Current therapies for T-cell exhaustion and cancer, such as those involving CTLA-4 blockade, face challenges in selectively targeting CTLA-4 without affecting CD28 interactions, leading to incomplete restoration of T-cell function and potential immune suppression.

Innovation Solution

Development of antibodies or antigen binding fragments that specifically bind to CTLA-4 with minimal to no binding to CD28, preventing CTLA-4 interaction with CD80/CD86 while allowing CD28 interactions to remain intact, thereby restoring T-cell function without inhibiting activation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibodies are used to block CTLA-4 interactions with CD80/CD86, then T-cell function is restored and anti-tumor immunity is enhanced, but CD28-driven activation pathways may be inadvertently inhibited leading to immune suppression

Engineering Contradiction:

ImproveT-cell function restorationVSAvoidimmune suppression

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The antibody is engineered to recognize and bind specifically to CTLA-4 with high affinity while displaying substantially no binding to CD28. This localized specificity ensures that the blocking effect is confined to CTLA-4-mediated inhibition pathways, allowing CD28-driven activation to proceed unimpeded, thus restoring T-cell function without causing immune suppression

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention segments the targeting function by designing an antibody that selectively targets only the CTLA-4 portion of the CD28/CTLA-4 ligand-receptor system. By focusing the blocking action exclusively on CTLA-4 and excluding CD28 from the inhibition scope, the therapy achieves precise modulation of T-cell regulation without broad immune suppression

Inventive Principle:

Principle #1Segmentation

2Object-affected harmful factors

If antibodies bind to both CTLA-4 and CD28, then CTLA-4-mediated suppression is blocked, but CD28-mediated T-cell activation is also inhibited reducing therapeutic efficacy

Engineering Contradiction:

ImproveCTLA-4-mediated suppressionVSAvoidT-cell activation

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The antibody exhibits differential binding properties with high affinity for CTLA-4 and substantially no binding to CD28. This localized specificity ensures that therapeutic blocking is confined to the inhibitory CTLA-4 pathway while the activatory CD28 pathway remains fully functional, resolving the contradiction between suppressing inhibition and maintaining activation

Inventive Principle:

Principle #3Local quality

3Reliability

If current CTLA-4 blockade therapies are used, then some T-cell function is restored, but the restoration is incomplete due to off-target effects on CD28

Engineering Contradiction:

ImproveT-cell function restorationVSAvoidselectivity of blockade

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The antibody is designed with enhanced local specificity to bind exclusively to CTLA-4 epitopes that are distinct from CD28 binding sites. This precise localization of binding activity achieves complete and selective blockade of CTLA-4-mediated suppression without any off-target effects on CD28, resulting in full restoration of T-cell function with high selectivity

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention replaces the non-specific mechanical blocking approach of prior antibodies with a precisely engineered molecular recognition system. The antibody's variable region is configured to recognize specific conformational epitopes on CTLA-4, substituting broad non-specific inhibition with targeted molecular interaction that achieves complete selectivity and full functional restoration

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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 antibodies effectively restore T-cell function and enhance anti-tumor immunity by selectively blocking CTLA-4-mediated immune suppression, leading to increased T-cell activation and cytokine production without impairing CD28-driven activation pathways.

Implementation Method 1

antibodies or antigen binding fragments that specifically bind to CTLA-4 with minimal to no binding to CD28

Methodology Applied

Scientific EffectAntibody-antigen binding:

Implementation Method 2

preventing CTLA-4 interaction with CD80/CD86 while allowing CD28 interactions to remain intact

Methodology Applied

Scientific EffectCompetitive inhibition:

Data Source

PatentUS11267887B2Anti-CTLA-4 antibodies

Publication Date: 2022.03.08 AGENCY FOR SCI TECH & RES

AI summary

Anti-CTLA-4 antibodies are disclosed. Also disclosed are compositions comprising such antibodies, and uses and methods using the same.