Antigen-Binding Proteins Targeting NRP-1 for Tumor Microenvironment Modulation

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Solution Overview

Problem

Current therapies fail to effectively antagonize Neuropilin 1 (NRP-1) without inducing autoimmune disease, which is crucial for modulating the immunosuppressive tumor microenvironment to inhibit tumor growth without affecting regulatory T cells outside the tumor environment.

Innovation Solution

Development of antigen-binding proteins (ABPs) specifically binding to human NRP-1, blocking interactions with semaphorin 3A and vascular endothelial cell growth factor A, thereby inhibiting Treg suppression and tumor growth without autoimmune adverse events.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If NRP-1 is completely depleted to inhibit tumor growth, then anti-tumor efficacy is improved, but autoimmune and inflammatory disorders occur

Engineering Contradiction:

Improveanti-tumor efficacyVSAvoidautoimmune and inflammatory disorders

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing ABPs that specifically target NRP-1 within the tumor microenvironment rather than systemically depleting all NRP-1. The ABPs are engineered to bind NRP-1 with high affinity in the tumor context, creating a localized therapeutic effect that preserves NRP-1 function in healthy tissues and prevents autoimmune side effects while maintaining anti-tumor efficacy

Inventive Principle:

Principle #3Local quality

2Reliability

If NRP-1 is targeted to modulate Treg activity in tumors, then Treg suppressive function is reduced, but specificity to tumor environment must be maintained

Engineering Contradiction:

ImproveTreg modulation efficacyVSAvoidtumor environment specificity

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent employs the intermediary principle by using ABPs as mediator molecules that bridge the gap between NRP-1 targeting and Treg modulation. These ABPs serve as intermediate agents that specifically recognize NRP-1 on Tregs within the tumor microenvironment and block its interaction with ligands like Sema4a, thereby modulating Treg function without directly depleting Tregs systemically

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If NRP-1 antagonists are used to reverse Treg suppressive activity, then anti-tumor immunity is enhanced, but autoimmune adverse events may occur

Engineering Contradiction:

Improveanti-tumor immunityVSAvoidautoimmune adverse events

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies segmentation by dividing the therapeutic approach into targeted segments: ABPs that specifically segment their action to NRP-1-expressing cells within the tumor microenvironment. This segmented targeting ensures that NRP-1 antagonism is delivered precisely where needed (in tumors) while sparing NRP-1 in peripheral tissues, thereby enhancing anti-tumor immunity without triggering autoimmune adverse events

Inventive Principle:

Principle #1Segmentation

Data Source

PatentEP3558365B1Anti-neuropilin antigen-binding proteins and methods of use thereof

Publication Date: 2023.09.13 POTENZA THERAPEUTICS INC

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AI summary

Provided herein are antigen-binding proteins (ABPs) that selectively bind to NRP-1 and its isoforms and homologs, and compositions comprising the ABPs. Also provided are methods of using the ABPs, such as therapeutic and diagnostic methods.