Anti-SIRPα Antibodies for Dual-Variant CD47 Blocking

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Solution Overview

Problem

Existing anti-SIRPα antibodies can only recognize variant 1 of the signal regulatory protein alpha (SIRPα) and fail to effectively block the interaction between SIRPα and CD47, limiting their ability to induce macrophage-mediated phagocytosis of cancer cells.

Innovation Solution

Development of anti-SIRPα antibodies with specific CDR sequences that bind to both variants v1 and v2 of SIRPα, blocking the interaction with CD47 and inducing macrophage-mediated phagocytosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing anti-SIRPα antibodies are used, then they can recognize variant 1 of SIRPα, but they fail to effectively block the interaction between SIRPα and CD47

Engineering Contradiction:

Improveblocking capability of SIRPα-CD47 interactionVSAvoidrecognition of SIRPα variants

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent designs anti-SIRPα antibodies with broad specificity to recognize both variant 1 and variant 2 of SIRPα, making the antibody universal across different SIRPα variants. This resolves the contradiction by enabling the antibody to effectively block the SIRPα-CD47 interaction regardless of which variant is present, thereby improving both blocking capability and adaptability simultaneously

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Productivity

If existing anti-SIRPα antibodies are used, then they can bind to SIRPα variant 1, but they cannot effectively induce macrophage-mediated phagocytosis of cancer cells

Engineering Contradiction:

Improvephagocytosis induction capabilityVSAvoideffectiveness in blocking CD47 interaction

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent modifies the binding parameters of the anti-SIRPα antibody by optimizing affinity and specificity through careful selection of complementarity determining regions (CDRs). This enhances the antibody's ability to block the SIRPα-CD47 interaction and subsequently improve macrophage-mediated phagocytosis of cancer cells, resolving the contradiction between productivity and reliability

Inventive Principle:

Principle #35Parameter changes

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 efficiently induce macrophage-mediated phagocytosis of cells expressing CD47, potentially enhancing cancer treatment by increasing phagocytosis of cancer cells.

Implementation Method 1

an antibody or fragment thereof having binding specificity to a wild-type human signal regulatory protein alpha (SIRPα) protein

Methodology Applied

Scientific EffectAntibody binding:

Implementation Method 2

effectively induce macrophage mediated phagocytosis of cells expressing CD47

Methodology Applied

Scientific EffectPhagocytosis:

Data Source

PatentUS12570742B2Anti-SIRPα monoclonal antibodies and uses thereof

Publication Date: 2026.03.10 LANOVA MEDICINES LTD CO

AI summary

Provided are antibodies or fragments thereof having binding specificity to both variant 1 and variant 2 of the signal regulatory protein alpha (SIRPα) protein. The antibodies and fragments can dose-dependently and efficiently block the interaction between SIRPα and CD47, and effectively induce macrophage-mediated phagocytosis of tumor cells expressing CD47.