GT468 Antibodies for Solid Cancer Therapy

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Solution Overview

Problem

Current antibody-based cancer therapies face challenges in selecting appropriate targets that balance toxicity and efficacy, particularly for solid cancers, where existing targets are expressed in normal tissues, limiting the therapeutic window and efficacy of treatments like Herceptin due to toxicity concerns.

Innovation Solution

Identification and utilization of GT468, a placenta-specific protein aberrantly activated and highly expressed in various tumor types, including breast, lung, and gastric cancers, as a target for antibody therapy, which is absent in normal tissues, allowing for targeted antitumor effects without harming healthy cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antibody targets are selected from currently approved targets (e.g., HER2, MUC-1, CD20), then therapeutic efficacy can be achieved, but toxicity increases due to expression of these targets on normal tissues

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidtoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the harmful aspect of target selection by identifying and excluding targets that are expressed on normal tissues. Instead of using conventional targets like HER2 or MUC-1 that cause toxicity, the invention isolates GT468 as a target that is exclusively expressed on tumor cells, thereby removing the source of harmful effects while preserving therapeutic efficacy.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent applies local quality by creating a differentiated targeting strategy where the antibody specifically recognizes GT468 on tumor cells while completely ignoring normal tissues. This localized specificity ensures that the therapeutic action is confined to the tumor site, preventing systemic toxicity to healthy organs and tissues.

Inventive Principle:
Principle #3Local quality

2Strength

If high-affinity antibodies are used against Ep-CAM, then binding strength increases, but toxicity increases due to accessibility of target on normal cells

Engineering Contradiction:
Improvebinding affinityVSAvoidtoxicity
Core Design Contradiction:
StrengthVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by creating a differentiated targeting strategy where the antibody specifically recognizes GT468 on tumor cells while completely ignoring normal tissues. This localized specificity ensures that the therapeutic action is confined to the tumor site, preventing systemic toxicity to healthy organs and tissues.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The patent changes the fundamental parameter of target selection from conventional targets with normal tissue expression (like Ep-CAM) to GT468, which has zero expression on normal tissues. This parameter change in target identity, rather than adjusting antibody affinity, eliminates the toxicity problem while maintaining high binding strength to the tumor target.

Inventive Principle:
Principle #35Parameter changes

3Reliability

If antibody targets are selected with high expression on tumor cells (e.g., HER2), then therapeutic window improves, but such targets are limited in availability for solid cancers

Engineering Contradiction:
Improvetherapeutic windowVSAvoidtarget availability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies universality by demonstrating that GT468 serves as a multi-functional target applicable to multiple solid cancer types including breast, lung, gastric, and other carcinomas. Unlike HER2 which is limited to specific cancers, GT468 provides a universal target that can be exploited across diverse solid tumor types, expanding the versatility of antibody therapy while maintaining a favorable therapeutic window.

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentEP2487189B8Monoclonal antibodies against GT468 for treatment of cancer
Publication Date: 2019.01.09 TRON TRANSLATIONALE ONKOLOGIE AN DER UNIVERSITAETSMEDIZIN DER JOHANNES GUTENBERG UNIV MAINZ GEMEINNUETZIGE GMBH

AI summary

The present invention provides antibodies useful as therapeutics for treating and/or preventing diseases associated with cells expressing GT468, including tumor-related diseases such as breast cancer, lung cancer, gastric cancer, ovarian cancer, and hepatocellular cancer.