Immuno-DASH and PGE2 Antagonist Combination for Toxicity-Limited Dosing

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Solution Overview

Problem

Immuno-DASH inhibitors, such as Talabostat, face dose-limiting toxicities and dosing issues that prevent effective administration in cancer treatment, limiting their therapeutic potential.

Innovation Solution

Combining immuno-DASH inhibitors with PGE2 antagonists, particularly cyclooxygenase inhibitors, to enhance safety and efficacy, increasing the maximum tolerated dose and therapeutic window of the immuno-DASH inhibitors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If immuno-DASH inhibitors are administered at high doses to achieve effective antitumor activity, then therapeutic efficacy is improved, but dose-limiting toxicities increase

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoiddose-limiting toxicities

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces PGE2 antagonists as intermediary agents that mediate between the immuno-DASH inhibitor and the host's inflammatory response. These antagonists block the harmful prostaglandin E2 pathway activated by DASH inhibition, thereby reducing toxicities like pneumonitis and edema while preserving the therapeutic immune activation effects on tumor cells

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent converts the harmful inflammatory response (pneumonitis, edema) caused by PGE2 overproduction into a beneficial outcome by using PGE2 antagonists to specifically block this pathway. The same immune activation that causes toxicity is harnessed to enhance antitumor immunity, while the antagonist prevents damage to healthy tissues

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

2Object-affected harmful factors

If the dose of immuno-DASH inhibitors is reduced to minimize toxicities, then safety is improved, but therapeutic efficacy decreases

Engineering Contradiction:

Improvetoxicity reductionVSAvoidtherapeutic efficacy

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent changes the therapeutic parameter landscape by introducing PGE2 antagonists that alter the dose-response relationship. This allows administration of higher doses of immuno-DASH inhibitors than would normally be tolerated, effectively expanding the therapeutic window and enabling doses that achieve both safety and efficacy simultaneously

Inventive Principle:

Principle #35Parameter changes

3Device complexity

If immuno-DASH inhibitors are used alone, then treatment simplicity is maintained, but the therapeutic window is limited

Engineering Contradiction:

Improvetreatment simplicityVSAvoidtherapeutic window

Core Design Contradiction:

Device complexityVSReliability

Solution Approach 1:

The patent merges two distinct therapeutic agents - immuno-DASH inhibitors and PGE2 antagonists - into a combination regimen. This combination creates a synergistic effect where the antagonist protects against toxicity while the inhibitor provides immune activation, thereby expanding the therapeutic window beyond what either agent could achieve alone

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS12478609B2Combination therapies using immuno-DASH inhibitors and PGE2 antagonists

Publication Date: 2025.11.25 TRUSTEES OF TUFTS COLLEGE

AI summary

Disclosed are combination therapies including administration of I-DASH inhibitors and PGE2 antagonists, and the use of such therapies in the treatment of cell proliferative diseases.