CBP/p300 Bromodomain Inhibitor and EGFR Inhibitor Combination for NSCLC

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Solution Overview

Problem

Current treatments for non-small cell lung cancer (NSCLC) with oncogenic alterations in the EGFR are limited by the development of resistance and lack of effective therapies, particularly when EGFR inhibitors become ineffective over time.

Innovation Solution

A combination of a CBP/p300 bromodomain inhibitor and an EGFR inhibitor is administered to treat NSCLC, where the CBP/p300 bromodomain inhibitor selectively binds to the bromodomain of CBP/p300, enhancing the therapeutic effect of the EGFR inhibitor and preventing resistance development.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If an EGFR inhibitor is administered alone to treat NSCLC with EGFR alterations, then initial therapeutic effect is achieved, but resistance develops over time reducing effectiveness

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidduration of therapeutic effect

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent combines a CBP/p300 bromodomain inhibitor with an EGFR inhibitor to create a dual-target therapy. This merging of two different mechanisms of action addresses the resistance problem by simultaneously blocking EGFR signaling and CBP/p300-mediated transcriptional programs, preventing the tumor from adapting to single-target inhibition.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The combination therapy applies preliminary anti-action by preemptively blocking both EGFR and CBP/p300 pathways before resistance can develop. The CBP/p300 inhibitor prevents the transcriptional reprogramming that typically enables resistance to EGFR inhibitors, thereby maintaining therapeutic effectiveness over time.

Inventive Principle:

Principle #9Preliminary anti-action

2Reliability

If a CBP/p300 bromodomain inhibitor is administered alone, then selective binding to CBP/p300 bromodomain is achieved, but no significant anti-proliferative effect is observed

Engineering Contradiction:

Improveselectivity of bindingVSAvoidanti-proliferative effect

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent merges the CBP/p300 bromodomain inhibitor with an EGFR inhibitor to achieve synergistic anti-proliferative effects. While the CBP/p300 inhibitor alone shows limited productivity, its combination with EGFR inhibition blocks both the signaling pathway and the transcriptional response, resulting in potent tumor growth suppression.

Inventive Principle:

Principle #5Merging (Combining)

3Duration of action of stationary object

If EGFR inhibitor treatment is continued long-term, then initial tumor control is maintained, but resistance alterations develop reducing therapeutic response

Engineering Contradiction:

Improveduration of tumor controlVSAvoidtherapeutic response

Core Design Contradiction:

Duration of action of stationary objectVSReliability

Solution Approach 1:

The patent merges EGFR inhibition with CBP/p300 bromodomain inhibition to maintain durable tumor control. The dual mechanism prevents the development of resistance alterations by simultaneously blocking the primary signaling pathway and the transcriptional adaptation responses, thereby preserving therapeutic response over long-term treatment.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The combination therapy applies preliminary anti-action by preemptively blocking CBP/p300-mediated transcriptional programs that would otherwise enable resistance development. This prevents the tumor from adapting to EGFR inhibition, maintaining reliable therapeutic response throughout extended treatment periods.

Inventive Principle:

Principle #9Preliminary anti-action

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The combination significantly prolongs the therapeutic effect of the EGFR inhibitor, inhibiting NSCLC cell proliferation, and delays the onset of resistance, offering a more effective treatment strategy for NSCLC with EGFR alterations.

Implementation Method 1

The CBP/p300 bromodomain inhibitor selectively binds to the bromodomain of CBP/p300

Methodology Applied

Scientific EffectBromodomain binding: Absorption (physical)

Implementation Method 2

The combination significantly prolongs the therapeutic effect of the EGFR inhibitor, inhibiting NSCLC cell proliferation

Methodology Applied

Scientific EffectInhibition of cell proliferation:

Data Source

PatentUS20230255966A1A combination of a CBP/p300 bromodomain inhibitor and an EGFR inhibitor for use in treating EGFR-mutant nsclc

Publication Date: 2023.08.17 TOLREMO THERAPEUTICS AG

AI summary

The present invention is inter alia concerned with a combination of a CBP/p300 bromodomain inhibitor and an EGFR inhibitor for use in the treatment of a patient suffering from NSCLC, wherein the NSCLC exhibits an oncogenic alteration in the EGFR.