Modified AXL Peptides Inhibit Metastasis via GAS6 Binding

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Solution Overview

Problem

Current cancer treatments lack effective methods to identify and inhibit metastatic cancer cells, particularly those involving the AXL, MER, and Tyro3 receptor tyrosine kinases and their ligand GAS6, which are crucial in tumor invasion and metastasis.

Innovation Solution

Development of inhibitor agents that target AXL, MER, and Tyro3 pathways by binding to GAS6 with increased affinity, including soluble variant polypeptides and antibody-conjugates, to inhibit the interaction between these receptors and their ligand, thereby blocking tumor invasion and metastasis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current cancer treatments are used, then general tumor mass can be reduced, but metastatic cancer cells cannot be specifically identified and inhibited

Engineering Contradiction:

Improveability to identify metastatic cancer cellsVSAvoidcomplexity of targeting system

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent modifies the binding parameters of inhibitor agents by creating variant polypeptides with altered amino acid sequences that specifically increase affinity for GAS6 ligand, enabling selective targeting of metastatic cells expressing AXL, MER, or Tyro3 receptors

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces soluble variant polypeptides as intermediary molecules that bind to GAS6 ligand with high affinity, blocking the interaction between GAS6 and cell surface receptors AXL, MER, or Tyro3 on metastatic cancer cells

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If inhibitor agents with increased affinity to GAS6 are developed, then binding affinity is improved, but manufacturing and characterization complexity increases

Engineering Contradiction:

Improvebinding affinity of inhibitor agentsVSAvoidease of producing inhibitor agents

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent segments the AXL receptor structure into soluble extracellular domain variants that can be independently produced and characterized, allowing modular optimization of binding affinity while simplifying manufacturing processes

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates multiple variant polypeptide copies with different amino acid substitutions to screen for optimal binding affinity, using standardized production protocols that facilitate high-throughput manufacturing of the most effective variants

Inventive Principle:

Principle #26Copying

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 proposed solution effectively inhibits tumor invasion and metastasis by enhancing the binding affinity of inhibitor agents to GAS6, potentially leading to improved treatment outcomes for cancers such as ovarian, breast, lung, and glioblastoma by targeting specific molecular markers.

Implementation Method 1

inhibitor agents that target AXL, MER, and Tyro3 pathways by binding to GAS6 with increased affinity

Methodology Applied

Scientific EffectLigand binding: Absorption (physical)

Data Source

PatentEP2931265B3Modified AXL peptides and their use in inhibition of AXL signaling in Anti-metastatic therapy

Publication Date: 2023.04.05 ARAVIVE BIOLOGICS INC

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AI summary

Compositions and methods are provided for alleviating cancer in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits activity of AXL, MER or Tyro3 protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL, MER or Tyro3 and its ligand GAS6.