Repebody Polypeptide Binding Complement C5a
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Solution Overview
Problem
Current therapeutic agents for immune diseases and sepsis caused by complement protein C5a have limited effectiveness and high production costs, with existing antibodies facing challenges in penetrating cells and achieving desired therapeutic outcomes.
Innovation Solution
Development of a novel polypeptide specifically binding to complement protein C5a using a repebody scaffold, fused with an N-terminal of internalin B protein and a modified leucine-rich repeat (LRR) protein, which is produced using a recombinant microorganism and encoded by a polynucleotide, to inhibit C5a activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antibodies are used as therapeutic agents, then binding capacity to target antigens is achieved, but production cost is high and penetration into cells is difficult due to large molecular weight
Solution Approach 1:
The patent creates a simplified copy of the antibody's binding function using a smaller protein scaffold (repebody) that mimics the antigen-binding capability of full antibodies. The repebody contains only the essential binding domain without the large Fc region, achieving comparable binding capacity at 1/5 the molecular weight, thereby reducing production costs while maintaining therapeutic efficacy
Solution Approach 2:
The invention extracts only the necessary antigen-binding portion from the complete antibody structure. By removing the Fc region and other non-essential domains, the patent creates a minimal functional unit (repebody) that retains binding capacity but eliminates the bulk that causes high production costs and poor cellular penetration
2Reliability
If conventional antibodies are used as therapeutic agents, then specific binding to antigens is achieved, but penetration into cells is difficult due to large molecular weight
Solution Approach 1:
The repebody creates a miniature copy of the antibody's variable region that preserves the specific binding interface while eliminating the heavy chain and light chain frameworks. This copied binding domain maintains affinity for target antigens but weighs only about 20-25 kDa compared to the full antibody's 150 kDa, enabling better tissue and cell penetration
Solution Approach 2:
The invention extracts solely the complementarity-determining regions and framework regions necessary for antigen recognition, discarding the Fc portion and other structural elements. This extracted binding fragment achieves specific binding comparable to full antibodies while reducing molecular weight to enable intracellular penetration
3Ease of manufacture
If repebody is used as an alternative to antibodies, then production cost is reduced and penetration into tissues is improved, but binding capacity must be maintained at therapeutic levels
Solution Approach 1:
The patent optimizes the repebody's binding parameters through consensus sequence design and affinity maturation. By adjusting amino acid sequences in the binding interface and selecting for higher affinity variants, the repebody achieves picomolar binding constants comparable to therapeutic antibodies, ensuring sufficient binding capacity despite the reduced molecular size
Solution Approach 2:
The repebody combines multiple stabilized beta-hairpin repeats into a composite protein structure that enhances both stability and binding affinity. This composite architecture allows the small protein to achieve therapeutic-level binding capacity through cooperative interactions across multiple repeat units, compensating for the lack of large molecular weight
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 polypeptide demonstrates enhanced binding specificity and affinity to C5a, potentially offering improved therapeutic effects for immune diseases and sepsis with reduced immunogenicity and production costs compared to traditional antibodies.
Implementation Method 1
Proteins are macromolecules that perform maintenance and function of life phenomena, and are responsible for a wide range of biological roles among various materials present in vivo. In order to perform these roles, protein-protein interactions should first be achieved
Data Source
AI summary
The present invention relates to novel polypeptide for binding to a complement protein C5a. More particularly, the present invention relates to polypeptide which can be bound to a complement protein C5a and inhibit the activation of same, polynucleotide which codes for the polypeptide, a recombinant vector which comprises the polynucleotide, a recombinant microorganism to which the recombinant vector has been introduced, a method for producing the polypeptide by means of the recombinant microorganism, and a pharmaceutical composition, for treating immune diseases or sepsis, containing the polypeptide. A polypeptide, according to the present invention, can be bound to a complement protein C5a, with higher affinity compared to being bound to a complement protein C5a receptor which is present in nature, and inhibits the activation of same, thus being widely utilized for development of formulation for preventing or treating diseases related to a complement protein C5a.