Dual-Target c-Kit and Siglec-6 Antibodies With Low Degranulation

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Solution Overview

Problem

There is a need for new and improved therapeutics that can effectively target c-Kit and/or siglec-6 to address mast cell-associated diseases or disorders such as allergies, inflammatory diseases, autoimmune diseases, and cancers.

Innovation Solution

Development of antibodies or antigen-binding fragments that can bind to both c-Kit and siglec-6, with specific affinity characteristics and minimal mast cell degranulation, offering reduced toxicity and internalization rates compared to reference antibodies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibodies target c-Kit and siglec-6 to treat mast cell-associated diseases, then therapeutic effectiveness is improved, but risk of mast cell degranulation and toxicity increases

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidmast cell degranulation and toxicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The antibody is engineered with differential binding affinities to different targets: high affinity for siglec-6 (KD < 100 nM) and moderate affinity for c-Kit (KD between 1 nM and 900 uM). This local quality differentiation allows selective inhibition of mast cell activation through siglec-6 binding while maintaining therapeutic efficacy through c-Kit binding, without triggering degranulation

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent specifies precise affinity parameters (KD values) as critical design criteria. By controlling the binding affinity parameters to specific ranges, the antibody achieves optimal therapeutic effect while avoiding the harmful threshold for mast cell degranulation. The affinity parameters are optimized to balance efficacy and safety

Inventive Principle:

Principle #35Parameter changes

2Reliability

If antibodies bind with high affinity to mast cell targets, then therapeutic effect is improved, but internalization rate and toxicity increase

Engineering Contradiction:

Improvetherapeutic effectVSAvoidinternalization rate and toxicity

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The antibody exhibits local quality in its binding characteristics: high affinity for siglec-6 (therapeutic effect) versus moderate affinity for c-Kit (avoiding internalization). This differential affinity profile ensures that the antibody remains bound to the cell surface long enough to exert therapeutic effect without being internalized at high rates, thereby reducing toxicity

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent applies partial action by requiring only moderate affinity for c-Kit (KD up to 900 uM) rather than high affinity, which is sufficient for therapeutic effect but avoids the excessive binding that would trigger internalization and toxicity. The siglec-6 binding affinity is optimized to the appropriate level without excess

Inventive Principle:

Principle #16Partial or excessive action

Data Source

PatentUS20260070975A1Antibodies targeting c-kit and/or siglec and uses thereof

Publication Date: 2026.03.12 SANTA ANA BIO INC

AI summary

Undesired mast cell activities are linked with various diseases or disorders, such as allergies, inflammatory diseases, autoimmune diseases, and cancers. There remains a need for new and improved therapeutics (e.g., for mast cell associated diseases or disorders) that can target c-Kit and/or siglec-6. Disclosed herein are molecules, such as antibodies and antibody fragments, capable of binding to c-Kit and/or siglec-6.