FGFR4 and EGFR Inhibitor Combination for HCC

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Solution Overview

Problem

Current treatments for hepatocellular carcinoma (HCC) lack effectiveness in reducing cell viability and tumor growth, particularly due to overexpression of fibroblast growth factor 19 (FGF19) and epidermal growth factor receptor (EGFR) pathways, which contribute to enhanced tumor growth and proliferation.

Innovation Solution

A combination therapy involving a selective FGFR4 inhibitor, Compound 1, and an EGFR inhibitor such as gefitinib, afatinib, or cetuximab is administered to synergistically reduce cell viability and inhibit tumor growth in HCC cells, potentially offering a more effective treatment approach than single-agent therapies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If single-agent therapy is used, then treatment simplicity is maintained, but effectiveness in reducing cell viability and tumor growth is insufficient

Engineering Contradiction:

Improveeffectiveness in reducing cell viability and tumor growthVSAvoidtreatment complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines Compound 1 (FGFR4 inhibitor) with EGFR inhibitors (gefitinib, afatinib, or cetuximab) into a fixed-ratio combination therapy. This merging of two targeted agents addresses the technical contradiction by improving anti-tumor effectiveness through dual pathway inhibition while maintaining treatment simplicity via fixed-dose combination formulations and standardized administration protocols.

Inventive Principle:

Principle #5Merging (Combining)

2Reliability

If combination therapy is used, then effectiveness in reducing cell viability and tumor growth is improved, but treatment complexity increases

Engineering Contradiction:

Improveeffectiveness in reducing cell viability and tumor growthVSAvoidease of administration

Core Design Contradiction:

ReliabilityVSEase of operation

Solution Approach 1:

The patent develops fixed-ratio combination formulations where Compound 1 and EGFR inhibitors are pre-combined in optimized proportions. This approach improves ease of administration by eliminating the need for clinicians to calculate and mix individual doses, while maintaining the synergistic effectiveness of the combination therapy.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent establishes specific dosage ratios and administration schedules for the combination therapy based on preclinical and clinical data. By optimizing parameters such as the ratio of Compound 1 to EGFR inhibitor, frequency of administration, and timing, the patent simplifies the operational complexity while preserving therapeutic effectiveness.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If higher doses of single agents are used, then treatment effectiveness may be improved, but toxicity and side effects increase

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidtoxicity and side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent utilizes fixed-ratio combination therapy with optimized dosage levels for each agent. This approach allows for lower individual doses of Compound 1 and EGFR inhibitors to achieve synergistic anti-tumor effects, thereby reducing toxicity and side effects compared to higher doses of single agents. The fixed ratios ensure consistent exposure levels that maximize efficacy while minimizing adverse effects.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS11357769B2Drug combinations for reducing cell viability and/or cell proliferation

Publication Date: 2022.06.14 EISAI R&D MANAGEMENT CO LTD

AI summary

Provided herein is a combination of agents for reducing cell viability and/or cell proliferation. The combination comprises an FGFR4 inhibitor and an EGFR inhibitor.