NMDA Receptor Antagonists for Tumor Angiogenesis

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Solution Overview

Problem

Current treatments for tumor angiogenesis lack effective novel therapeutics and methods for screening angiogenesis regulation potency, with existing substances often having toxicity issues or limited applicability, necessitating the development of new NMDA receptor antagonists to address uncontrolled angiogenesis in cancer and other diseases.

Innovation Solution

Development of NMDA receptor antagonists, including small organic molecules, antibodies, and polypeptides that block NMDA receptor activation or inhibit its expression, which can be used to treat tumor angiogenesis by targeting the N-Methyl-D-aspartate receptor (NMDAR) to regulate angiogenic processes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing anti-angiogenic substances (protamine, heparin, steroids, fumagillin) are used to inhibit tumor angiogenesis, then angiogenesis inhibition is achieved, but toxicity limits their practical use or they have limited applicability

Engineering Contradiction:
Improveangiogenesis inhibition efficacyVSAvoidtoxicity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the molecular target parameter from existing anti-angiogenic pathways to the NMDA receptor pathway. By identifying and targeting a completely different molecular mechanism (NMDA receptor-mediated angiogenesis), the patent achieves angiogenesis inhibition while avoiding the toxicity problems associated with previously used substances like protamine, heparin, and fumagillin.

Inventive Principle:
Principle #35Parameter changes

2Object-affected harmful factors

If new anti-angiogenic therapeutics are developed to overcome toxicity issues, then safety is improved, but lack of effective novel therapeutics persists

Engineering Contradiction:
Improvetoxicity reductionVSAvoideffective novel therapeutics availability
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent segments the anti-angiogenic therapeutic landscape by targeting a specific, previously untapped pathway (NMDA receptor) rather than using broad-spectrum inhibitors. This focused approach on a discrete molecular target enables the development of novel therapeutics with improved safety profiles while maintaining efficacy.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent introduces NMDA receptor antagonists as intermediary substances that block the glutamate-NMDA receptor pathway to inhibit angiogenesis. These antagonists serve as a new class of mediators that indirectly control angiogenesis through a different mechanism than previously used direct angiogenic factor inhibitors, thereby providing effective novel therapeutics with reduced toxicity.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If conventional angiogenesis inhibitors are used, then tumor angiogenesis is suppressed, but there is a high need in the art for novel therapeutically active substances

Engineering Contradiction:
Improveangiogenesis suppressionVSAvoidnovel therapeutically active substances
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

Instead of continuing to develop modifications of existing anti-angiogenic agents, the patent inverts the approach by completely changing the molecular target from traditional angiogenic factors to the NMDA receptor system. This inversion provides truly novel therapeutically active substances that address the unmet need in the art while maintaining reliable angiogenesis suppression.

Inventive Principle:
Principle #13The other way round (Inversion)

Data Source

PatentEP3383429B1Nmdar antagonists for the treatment of tumor angiogenesis
Publication Date: 2020.10.14 INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)
  • EP3383429B1 patent drawingFigure 1A~1B
  • EP3383429B1 patent drawingFigure 1C~1D
  • EP3383429B1 patent drawingFigure 1E

AI summary

The present invention relates to an N-Methyl-D-aspartate (NMDA) receptor antagonist, for use in the treatment of diseases associated with angiogenesis such as tumor angiogenesis, ocular neovascular disease, Age-related macular degeneration (AMD).