KRAS G12C Modulating Compound Combination Therapy

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current treatments for KRAS mutant cancers, particularly those with the G12C mutation, are inadequate, as direct targeting of KRAS has proven difficult and existing therapies do not effectively induce robust cell death or apoptosis, highlighting a need for improved combination therapies.

Innovation Solution

Administering a KRAS, HRAS, or NRAS G12C mutant modulating compound in combination with additional therapeutic agents such as EGFR inhibitors, PI3K inhibitors, or chemotherapeutic agents to synergistically inhibit mutant KRAS activity and induce apoptosis in cancer cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If direct targeting of KRAS is attempted, then specific inhibition of mutant KRAS activity can be achieved, but robust cell death and apoptosis are not effectively induced

Engineering Contradiction:
Improvespecific inhibition of mutant KRAS activityVSAvoidrobust cell death and apoptosis induction
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent combines a KRAS G12C modulating compound with additional therapeutic agents (such as EGFR inhibitors, PI3K inhibitors, or chemotherapeutic agents) to create a combination therapy that achieves both specific KRAS inhibition and robust cell death induction, resolving the contradiction between specificity and effectiveness

Inventive Principle:
Principle #5Merging (Combining)

2Ease of operation

If existing therapies are used for KRAS mutant cancers, then treatment can be administered, but effective treatment options are lacking and survival chances remain extremely low

Engineering Contradiction:
Improvetreatment administrationVSAvoidclinical outcomes and survival rates
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent changes the therapeutic parameter from monotherapy to combination therapy, incorporating a KRAS G12C modulating compound with additional therapeutic agents, which dramatically improves clinical outcomes and survival rates while maintaining ease of administration

Inventive Principle:
Principle #35Parameter changes

3Productivity

If KRAS depletion is performed in cancer cells, then growth inhibition is observed, but robust induction of cell death or apoptosis does not occur

Engineering Contradiction:
Improvegrowth inhibitionVSAvoidcell death induction
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent introduces additional therapeutic agents as intermediaries that work in conjunction with the KRAS modulating compound to bridge the gap between growth inhibition and cell death induction, enabling robust apoptosis while maintaining growth suppression

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentEP3193851B1Combination therapies for treatment of cancer
Publication Date: 2020.10.21 ARAXES PHARMA LLC
  • EP3193851B1 patent drawingFigure 1
  • EP3193851B1 patent drawingFigure 2A~2B
  • EP3193851B1 patent drawingFigure 3A~3D

AI summary

Combination therapies for treatment of cancers associated with mutations in the KRAS gene are provided. Compositions comprising therapeutic agents for treatment of cancers associated with mutations in the KRAS gene are also provided.