Conditionally Active Anti-EpCAM Antibodies for Tumor-Selective Binding

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Solution Overview

Problem

Existing anti-EpCAM antibodies used in cancer therapy often cause side effects due to their affinity for EpCAM expressed on normal epithelial cells, limiting their therapeutic window and efficacy.

Innovation Solution

Development of anti-EpCAM antibodies or antibody fragments with enhanced binding affinity to tumor-specific EpCAM and reduced affinity to normal tissues, designed to minimize side effects and allow higher dosages for targeted cancer treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing anti-EpCAM antibodies are used to target tumor cells, then therapeutic effect is improved, but side effects occur due to affinity for EpCAM on normal epithelial cells

Engineering Contradiction:

Improvetherapeutic effectVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The antibody is engineered to have different binding affinities in different locations: high affinity in the acidic tumor microenvironment and low affinity in normal physiological conditions. This spatial differentiation of binding properties allows selective targeting of tumors while sparing normal tissues expressing EpCAM.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The antibody's binding affinity is made responsive to pH parameter changes. The modified antibody exhibits enhanced binding at acidic pH (tumor microenvironment, pH 6.5-6.8) and reduced binding at neutral pH (normal tissues, pH 7.4), enabling conditional activation at the target site.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If antibody affinity to EpCAM is increased to improve targeting, then therapeutic efficacy is improved, but affinity to normal tissues also increases causing more side effects

Engineering Contradiction:

Improvetargeting efficacyVSAvoidaffinity to normal tissues

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The antibody's binding affinity is transformed from a static property to a dynamic one that responds to environmental pH conditions. The antibody automatically adjusts its binding strength based on the local pH, being strong in acidic tumor environments and weak in neutral normal tissue environments.

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The antibody is pre-modified with pH-sensitive characteristics before administration, enabling it to automatically differentiate between tumor and normal tissues upon exposure to different pH environments without requiring additional activation steps.

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS20260053904A1Conditionally active Anti-epcam antibodies, antibody fragments, their immunoconjugates and uses thereof

Publication Date: 2026.02.26 BIOATLA LLC

AI summary

Isolated polypeptides having a heavy chain variable region and/or light chain variable region that specifically binds to EpCAM protein as well as antibodies and antibody fragments containing the heavy chain variable region and/or the light chain variable region that bind to EpCAM protein. Pharmaceutical compositions and kits comprising the polypeptide and antibodies and antibody fragments containing the polypeptide are also provided.