Bi-Functional Fusion Protein Inhibits Complement Activation to Prevent Bone Loss

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current treatments for periodontitis, a chronic inflammatory disease affecting the periodontium, are inadequate in addressing the role of the complement system in disease progression and bone loss, particularly in modulating the inflammatory response and osteoclastogenesis.

Innovation Solution

A bi-functional fusion protein is developed, comprising a complement C4b binding motif with decay-accelerating activity, a complement C3b binding motif with cofactor domain, and an Fc region, which inhibits the complement signaling pathway, potentially mitigating periodontitis progression by regulating C3b and C4b activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for periodontitis are used, then general inflammatory symptoms may be managed, but complement system activation and bone loss progression are not effectively addressed

Engineering Contradiction:

Improveeffectiveness of periodontitis treatmentVSAvoidcomplement system activation and bone loss

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The bi-functional fusion protein serves as an intermediary molecule that simultaneously binds to C3b and C4b complement components, blocking their activation pathways. This mediator approach directly addresses the unmet need of inhibiting complement system activation while treating periodontitis, resolving the contradiction between managing general inflammation and preventing complement-mediated bone loss

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The fusion protein combines multiple functional domains (C3b binding motif, C4b binding motif, and Fc region) into a single molecule that can simultaneously inhibit both classical and alternative complement pathways. This multi-functional design allows one treatment agent to address multiple harmful mechanisms (complement activation and osteoclastogenesis) that single-target therapies cannot effectively manage

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Object-affected harmful factors

If complement activation is inhibited to prevent bone loss, then osteoclastogenesis may be reduced, but the complexity of the treatment mechanism increases

Engineering Contradiction:

Improveosteoclastogenesis and bone lossVSAvoidtreatment mechanism complexity

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent merges separate complement inhibition functions into a single bi-functional fusion protein molecule. By combining the C3b binding motif and C4b binding motif in one protein structure, the treatment achieves dual pathway inhibition (classical and alternative) through a unified mechanism, reducing the complexity of requiring multiple separate agents while effectively preventing osteoclastogenesis

Inventive Principle:

Principle #5Merging (Combining)

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 bi-functional fusion protein effectively inhibits complement activation pathways, demonstrating significant inhibition of both classical and alternative complement pathways, and shows protective effects against periodontitis-induced bone loss in animal models, suggesting its potential as a therapeutic agent for periodontal diseases.

Implementation Method 1

The activation of the complement signaling cascade involves an activation cascade of signaling proteins, as well as proteolytic cleavages of serum proteins. These activation pathways of complement could be exerted via three distinct mechanisms, namely the classical, lectin (MBL), and alternative pathways

Methodology Applied

Scientific EffectComplement system activation:

Implementation Method 2

the complement C4b binding motif comprises a decay-accelerating activity (DAA) domain derived from complement receptor I

Methodology Applied

Scientific EffectDecay-accelerating activity:

Implementation Method 3

the complement C3b binding motif comprises a cofactor domain (CA) domain derived from complement receptor I

Methodology Applied

Scientific EffectCofactor activity:

Implementation Method 4

an Fc region (fragment crystallizable region)

Methodology Applied

Scientific EffectFc region binding:

Data Source

PatentUS20240391976A1Bi-Functional Fusion Proteins to Complement Pathways and Method of Inhibiting Bone Resorption

Publication Date: 2024.11.28 AP BIOSCIENCES INC

AI summary

The invention provides aerodynamic lift, or downward thrust for the amphibious environment, by means of two conical frames that are opposed at the bases and counter-rotating, thus cancelling out the opposing torque moment when rotating, being provided with concentric rows of fixed and retractable blades having variable angle of attack, arranged along the generatrix, separated by the fixed central area of the frame, where the power plant and the electro-mechanical elements that enable its operation are located, the cabins being situated in the conoidal hollow space of both, thus forming a body of lenticular geometry. The invention is provided with an electro-aerodynamic stabilisation system and landing gear (T), propulsion and manoeuvring being provided by pressurised air supplied through variable-area nozzles, and by the thrust due to the tilting of its axis (Y), with a fairing. Its functions and performance are similar to those of a helicopter.