CTLA-4 Antibodies Modulating Immune Tolerance

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Solution Overview

Problem

Current therapies for diseases associated with CTLA-4, such as autoimmune disorders and cancer, face limitations in effectively modulating CTLA-4 activity to enhance immune responses or inhibit immune tolerance.

Innovation Solution

Development of antibodies that specifically bind to CTLA-4 with high affinity, including human, chimeric, and humanized antibodies, to block or antagonize its signaling, thereby inhibiting its interaction with B7 ligands and modulating immune responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CTLA-4 signaling is left unmodulated, then immune tolerance is maintained and autoimmune reactions are prevented, but immune responses to tumors and pathogens are insufficient

Engineering Contradiction:

Improveimmune toleranceVSAvoidimmune response

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent introduces an intermediary molecule (anti-CTLA-4 antibody or CTLA-4 Ig fusion protein) that mediates the modulation of CTLA-4 signaling. This intermediary selectively blocks the inhibitory interaction between CTLA-4 and B7 ligands, allowing immune responses to be enhanced without completely abolishing CTLA-4 function, thus resolving the contradiction between maintaining immune tolerance and enhancing immune response.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the functional parameter of CTLA-4 by using antibodies or fusion proteins that alter its binding affinity or signaling capacity. By modifying how CTLA-4 interacts with B7 ligands through these therapeutic agents, the system can dynamically adjust the balance between immune tolerance and immune activation depending on the disease context.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If CTLA-4 activity is blocked to enhance immune responses, then anti-tumor and anti-pathogen immunity is improved, but autoimmune disorders may be exacerbated

Engineering Contradiction:

Improveimmune responseVSAvoidautoimmune reactions

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies partial action by using CTLA-4 Ig fusion protein that selectively blocks CTLA-4/B7 interactions in specific contexts (such as during viral infection or tumor immunity) without completely abolishing CTLA-4 function. This partial blockade allows enhancement of desired immune responses while minimizing the risk of triggering autoimmune reactions that would result from complete blockade.

Inventive Principle:

Principle #16Partial or excessive action

3Reliability

If high affinity antibodies are used to block CTLA-4, then immune response modulation is effective, but specificity and off-target effects become critical concerns

Engineering Contradiction:

ImproveCTLA-4 binding affinityVSAvoidbinding specificity

Core Design Contradiction:

ReliabilityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent uses highly specific anti-CTLA-4 antibodies as intermediaries that are engineered to bind exclusively to CTLA-4 with high affinity. These antibodies serve as selective mediators that modulate CTLA-4 function without affecting other immune checkpoint molecules or receptors, thereby achieving effective immune response modulation while maintaining high binding specificity and avoiding off-target effects.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS11208483B2CTLA-4 antibodies and uses thereof

Publication Date: 2021.12.28 SHANGHAI KANDA BIOTECHNOLOGY CO LTD

AI summary

Human antibodies which specifically bind to human CTLA-4, and related antibody-based compositions and molecules, are disclosed. Also disclosed are pharmaceutical compositions comprising the human antibodies, and therapeutic and diagnostic methods for using the human antibodies.