Modified Complement Regulator Proteins for Longer Serum Half-Life
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Solution Overview
Problem
Existing therapeutics for regulating the alternative complement pathway suffer from issues such as short serum half-life, high cost, side effects, and risks associated with functional FH polymorphisms, limiting their effectiveness in treating complement-related disorders.
Innovation Solution
Development of a recombinant complement regulator protein comprising specific FH and FHR CCP domains, linked by flexible peptides, designed to enhance serum stability and dimerization, thereby improving serum half-life and reducing the risk of functional FH polymorphisms.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If existing therapeutics are used to regulate the alternative complement pathway, then complement activation is inhibited, but serum half-life is short and therapeutic efficacy is limited
Solution Approach 1:
The therapeutic protein is divided into multiple CCP domains (specifically CCP1-CCP4 or CCP1-CCP5) that can be independently configured. This segmentation allows optimization of each domain's function while extending the overall protein half-life through controlled degradation patterns of individual domains.
Solution Approach 2:
The invention creates a composite protein structure by combining multiple CCP domains from Factor H or Factor H-related proteins into a single therapeutic molecule. This composite structure integrates the regulatory functions of different domains while achieving prolonged serum half-life and improved therapeutic efficacy simultaneously.
2Reliability
If full-length Factor H is used, then complement regulation is achieved, but cost is high and manufacturing complexity increases
Solution Approach 1:
The invention extracts only the essential CCP domains (CCP1-CCP4 or CCP1-CCP5) from the full-length Factor H protein. This extraction removes non-essential portions while retaining the core complement regulation function, thereby simplifying manufacturing and reducing costs.
Solution Approach 2:
By segmenting Factor H into discrete CCP domains, the invention creates a simplified protein structure that is easier to manufacture with controlled complexity. The modular domain structure allows for standardized production protocols while maintaining therapeutic efficacy.
3Object-affected harmful factors
If existing complement therapeutics are administered, then complement activation is reduced, but side effects occur and functional FH polymorphism risks remain
Solution Approach 1:
The therapeutic protein exhibits local quality through its specific CCP domain configuration, which provides targeted complement regulation at the molecular level. This localized precision reduces off-target effects and minimizes side effects while maintaining effective complement inhibition where needed.
Solution Approach 2:
The invention changes the structural parameters of the therapeutic protein by using specific CCP domain combinations and modifications. These parameter changes optimize the protein's regulatory function while reducing its immunogenicity and eliminating associations with functional FH polymorphisms, thereby minimizing side effects.
Data Source
AI summary
Certain embodiments of the present invention relate to regulation of the innate immune system and complement activation. In particular, but not exclusively certain embodiments relate to a complement regulator protein and pharmaceutical compositions thereof for use in the treatment of diseases associated with or mediated by the alternative complement pathway and methods of treating such diseases and other subject matter.