Factor H CCP19-20 Modulator Protein for Complement Pathway Inhibition

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Solution Overview

Problem

There is a need for improved complement inhibitors that effectively regulate the classical and lectin pathways of complement activation, addressing the limitations of existing technologies.

Innovation Solution

A modulator protein comprising a regulator module that regulates the classical and/or lectin pathways of complement activation, combined with a binding module consisting of CCP domains 19 and 20 of factor H, to inhibit these pathways and prevent tissue damage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing complement inhibitors are used, then complement activation is partially regulated, but they fail to effectively inhibit both classical and lectin pathways simultaneously

Engineering Contradiction:

Improvecomplement pathway regulation efficacyVSAvoidmulti-pathway inhibition capability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines CCP domains 19 and 20 of factor H into a single modulator protein structure that can simultaneously regulate both the classical and lectin pathways of complement activation, achieving multi-pathway inhibition with a unified molecular entity

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The modulator protein comprising CCP domains 19 and 20 is designed to perform multiple functions: it can bind to C4b and regulate the classical pathway while also binding to MBL and regulating the lectin pathway, making it a universal regulator for both complement activation pathways

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Productivity

If complement activation is allowed to proceed, then opsonisation and immune clearance functions are achieved, but tissue damage occurs due to uncontrolled activation

Engineering Contradiction:

Improveimmune clearance efficiencyVSAvoidtissue damage from complement activation

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The modulator protein acts as a negative feedback regulator that monitors complement activation levels and provides corrective inhibition when activation exceeds physiological thresholds, preventing tissue damage while allowing necessary immune functions to proceed

Inventive Principle:

Principle #23Feedback

Solution Approach 2:

The modulator protein serves as an intermediary molecule that mediates between the complement system's immune clearance functions and host tissue protection, selectively inhibiting harmful activation while permitting beneficial opsonisation and pathogen clearance

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentEP4559472A1Complement modulator

Publication Date: 2025.05.28 UNIV ULM

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AI summary

The present invention relates to a modulator protein comprising (i) a regulator module regulating the classical pathway of complement activation and/or the lectin pathway of complement activation and (ii) a binding module comprising, preferably consisting of, CCP domains 19 and 20 of a factor H; for use in preventing and/or treating a disease caused and/or aggravated by an activation of the classical and/or lectin pathway of complement activation, and to modulator proteins, methods, and kit related thereto.