Dual-Target Binding Molecule for Osteoarthritis Pain Relief

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Solution Overview

Problem

Current pain management options, particularly for chronic and osteoarthritic pain, are inadequate, with many patients not effectively managing their pain with available treatments, and there is a need for safer and more effective analgesics due to the limitations of existing medications like NSAIDs and opioid use.

Innovation Solution

A subcutaneous fixed dose of a binding molecule comprising an NGF antagonist portion and a TNFα antagonist portion is administered, which includes an anti-NGF antibody or antigen-binding fragment and a soluble TNFα binding fragment of TNFR, to effectively reduce or prevent pain, especially in osteoarthritic pain, often in combination with other pain medications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If NSAIDs are used for pain management, then pain relief is achieved, but cardiovascular mortality risk increases

Engineering Contradiction:

Improvepain relief effectivenessVSAvoidcardiovascular mortality risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The binding molecule is divided into two separate functional domains: an NGF antagonist portion and a TNFα antagonist portion. Each domain independently targets a different pain pathway, allowing the molecule to provide comprehensive pain relief through multiple mechanisms while avoiding the cardiovascular side effects associated with NSAID monotherapy

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention creates a composite binding molecule that combines NGF and TNFα antagonist functionalities into a single molecular structure. This composite approach integrates two different therapeutic mechanisms (NGF antagonism and TNFα antagonism) to achieve synergistic pain relief without the harmful cardiovascular effects of traditional NSAIDs

Inventive Principle:

Principle #40Composite materials

2Reliability

If traditional pain medications are used, then some pain relief is provided, but many patients do not achieve effective pain management

Engineering Contradiction:

Improvepain management effectivenessVSAvoidtreatment coverage for different patient populations

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The binding molecule is designed with dual functionality, containing both NGF antagonist and TNFα antagonist portions that can address multiple types of pain mechanisms simultaneously. This multi-functional design makes the single molecule effective across diverse patient populations and pain conditions, including osteoarthritic pain, neuropathic pain, and inflammatory pain, thereby achieving universal applicability

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The invention changes the therapeutic parameter from single-target NSAID or opioid monotherapy to dual-target NGF and TNFα antagonism. By targeting multiple pain pathways simultaneously, the binding molecule achieves superior and more consistent pain relief across different patient populations, including those who failed to respond to traditional single-mechanism treatments

Inventive Principle:

Principle #35Parameter changes

3Device complexity

If single-antagonist molecules are used, then one pain pathway is blocked, but multiple pain mechanisms remain active

Engineering Contradiction:

Improvemolecular structure simplicityVSAvoidcomprehensive pain control

Core Design Contradiction:

Device complexityVSReliability

Solution Approach 1:

The invention merges two separate antagonist functions (NGF antagonism and TNFα antagonism) into a single binding molecule. The NGF antagonist portion and TNFα antagonist portion are combined within one molecular structure, enabling simultaneous blockade of multiple pain pathways and achieving comprehensive pain control that exceeds the capability of single-antagonist molecules

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS20240026036A1Compounds and methods for treating pain

Publication Date: 2024.01.25 MEDIMMUNE LTD

AI summary

The disclosure provides novel methods and dosage regimens for use in treating or preventing pain, wherein the binding molecule comprises an NGF antagonist domain and a TNFα antagonist domain, wherein the NGF antagonist domain is an anti-NGF antibody or an antigen-binding fragment thereof and wherein the TNFα antagonist domain comprises a soluble TNFα binding fragment of TNFR.