PRO 140 Monoclonal Antibody CCR5 Receptor Binding Selectivity

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Solution Overview

Problem

There is a need for improved competitive inhibitors to the CCR5 receptor that can effectively inhibit the CCL5/CCR5 receptor axis without triggering unintended side effects, offering longer-lasting and less severe therapeutic benefits for conditions like autoimmune disorders, cancer, and inflammation, while minimizing dosing demands and adverse reactions.

Innovation Solution

The use of PRO 140, a humanized monoclonal antibody that binds to the CCR5 receptor without agonist activity, thereby reducing downstream immunomodulatory effects such as cAMP levels and cell migration, providing a therapeutic approach that specifically targets the CCL5/CCR5 axis without inducing counterproductive responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If competitive inhibitors bind to CCR5 receptor to inhibit CCL5/CCR5 axis, then therapeutic effect is improved, but unintended side effects and adverse reactions occur

Engineering Contradiction:

Improvetherapeutic effectVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by designing inhibitors with specific molecular structures that selectively target the CCL5/CCR5 interaction site while sparing other CCR5 ligand interactions. This selectivity ensures therapeutic effect on CCL5-mediated inflammation while minimizing unintended side effects from blocking other chemokine pathways.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent employs parameter changes by optimizing inhibitor binding affinity and selectivity parameters. By carefully tuning the binding characteristics of competitive inhibitors to match CCL5-CCR5 interaction parameters while differentiating from other chemokine-receptor interactions, the patent achieves effective inhibition with reduced adverse reactions.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If higher doses of competitive inhibitors are administered to enhance therapeutic effect, then disease progression is slowed, but dosing demands and adverse reactions increase

Engineering Contradiction:

Improvedisease progression controlVSAvoiddosing demands

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The patent applies parameter changes by optimizing the potency and bioavailability parameters of competitive inhibitors. Through structural optimization, the inhibitors achieve high binding affinity for CCL5/CCR5 axis, allowing effective disease progression control at lower doses, thereby reducing dosing demands and associated adverse reactions.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If competitive inhibitors block CCR5 receptor to reduce inflammation, then therapeutic benefit is achieved, but duration of action and therapeutic persistence are limited

Engineering Contradiction:

Improvetherapeutic benefitVSAvoidtherapeutic persistence

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent employs parameter changes by optimizing the kinetic parameters of inhibitor-receptor binding. Through structural modifications, the competitive inhibitors achieve prolonged residence time and sustained binding to CCR5 receptor, extending therapeutic persistence while maintaining reliable therapeutic benefit.

Inventive Principle:

Principle #35Parameter changes

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

PRO 140 effectively downregulates the effects of CCL5 binding on the CCR5 receptor, reducing inflammation and disease progression in various conditions, including autoimmune disorders and cancer, with a favorable safety profile and reduced side effects, allowing for dose-dependent immunomodulatory treatment.

Implementation Method 1

PRO 140, a humanized monoclonal antibody that binds to the CCR5 receptor without agonist activity

Methodology Applied

Scientific EffectMonoclonal antibody binding:

Data Source

PatentUS11584797B2Inhibition of CCL5 ligand binding to CCR5 receptor and alteration of CCR5/CCL5 axis signaling in inflammation, cancer, autoimmune, and other conditions

Publication Date: 2023.02.21 CYTODYN INC

AI summary

Methods for the therapeutic use of competitive inhibitors of the CCR5/CCL5 axis that express antagonist activity for RANTES (CCL5) for immunomodulatory treatment of subjects in need thereof. The competitive inhibitors may not have CCL5 agonist activity and can be used to inhibit, interrupt, block, mitigate, slow the progress of, and/or treat inflammation and/or various other CCR5/CCL5 axis signaling dependent down-stream activities associated with transplantation, including graft versus host disease, autoimmune disorders, infectious agents, chronic inflammation, and cancer, etc.