Multispecific Anti-PDL1 Antibodies for Reduced Red-Cell Binding

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Solution Overview

Problem

There is a need for the development of PDL1- and CD47-targeting molecules to enhance immune therapy and cancer treatment, particularly to inhibit immune escape by tumor cells and reduce binding to red blood cells.

Innovation Solution

Development of monoclonal antibodies and multispecific antibodies that bind specifically to PDL1 and CD47 with high affinity, including single domain antibodies and novel multispecific antibodies that reduce binding to red blood cells, to enhance immune response against tumor cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional anti-CD47 antibodies are used to target tumor cells, then immune response against tumor cells is enhanced, but binding to red blood cells occurs causing off-target effects

Engineering Contradiction:

Improvespecificity of antibody bindingVSAvoidoff-target binding to red blood cells

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by engineering the anti-CD47 antibody to have different binding properties at different locations - high affinity for CD47 on tumor cells while having reduced binding to CD47 on red blood cells. This is achieved through selective affinity modification that creates location-specific binding behavior, allowing the antibody to distinguish between tumor and normal cells expressing the same antigen.

Inventive Principle:

Principle #3Local quality

2Reliability

If PD1/PDL1 interaction is inhibited to mediate antitumor activity, then immune escape by tumor cells is blocked, but T cell activation and cytokine secretion are suppressed under physiological conditions

Engineering Contradiction:

Improveanti-tumor efficacyVSAvoidinhibition of T cell activation

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies inversion by reversing the normal physiological function of the PD1/PDL1 interaction. Instead of allowing the interaction to occur (which would suppress T cell activation), the antibody blocks the interaction to prevent immune escape. This inverts the normal immune suppression mechanism to achieve tumor cell killing while maintaining T cell function against tumors.

Inventive Principle:

Principle #13The other way round (Inversion)

3Reliability

If multispecific antibodies targeting both PDL1 and CD47 are developed, then anti-tumor efficacy is improved through dual targeting, but antibody complexity and manufacturing difficulty increase

Engineering Contradiction:

Improveanti-tumor efficacyVSAvoidantibody structure complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies merging by combining two separate antibody functions into a single multispecific antibody molecule. The antibody is engineered to simultaneously target both PDL1 and CD47, merging the anti-PDL1 and anti-CD47 functionalities into one therapeutic agent. This approach consolidates multiple mechanisms of action into a single platform, reducing the need for combination therapies.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent applies multi-functionality by designing an antibody that performs multiple functions simultaneously - blocking PD1/PDL1 interaction to prevent immune escape and binding CD47 to enhance phagocytosis of tumor cells. This universal antibody platform addresses multiple aspects of tumor immunity through a single molecule, improving overall anti-tumor efficacy while simplifying treatment regimens.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250326848A1Anti-PDL1 antibodies, multispecific antibodies and methods of use

Publication Date: 2025.10.23 SHANGHAI HENLIUS BIOTECH INC

AI summary

The present disclosure relates to antibodies and antibody derivatives that bind to PDL1 and methods of using the same. In certain embodiments, the antibody or antibody derivative disclosed herein comprises a single domain antibody that binds to PDL1. In certain embodiments, the antibody derivative is a multispecific antibody that binds to PDL1 and an additional antigen, e.g., CD47.