Fusion Proteins Enhancing Siglec Binding for Inflammation

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Solution Overview

Problem

Current biological products lack superior Siglec-binding and enhanced anti-inflammation activities, necessitating the development of safer and more potent therapies for conditions associated with tissue injuries and inflammatory responses.

Innovation Solution

Development of glycosylated and/or sialylated core peptides and their fusion proteins with the Fc fragment of human immunoglobulin, specifically designed to regulate Siglec-related signaling and bind to HMGB1, providing effective anti-inflammatory effects.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current biological products are used, then basic immune response regulation is achieved, but Siglec-binding activity and anti-inflammatory efficacy are insufficient

Engineering Contradiction:
Improveanti-inflammatory efficacyVSAvoidSiglec-binding activity
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent creates fusion proteins combining MUC1 tandem repeat core peptide with Fc fragment of human immunoglobulin. This composite structure integrates the Siglec-binding capability of MUC1 (providing anti-inflammatory efficacy) with the effector functions of Fc (enhancing versatility and potency), thereby simultaneously improving both reliability and adaptability

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent modifies the core peptide structure by incorporating specific tandem repeats with defined amino acid sequences (SEQ ID NO: 2-4) and controlling glycosylation/sialylation levels. These parameter changes in molecular structure and composition directly enhance Siglec-binding affinity and subsequent anti-inflammatory activity

Inventive Principle:
Principle #35Parameter changes

2Reliability

If MUC1 tandem repeat core peptide is used to bind HMGB1 and regulate immune response, then anti-inflammatory activity is enhanced, but molecular complexity and glycosylation requirements increase

Engineering Contradiction:
Improveimmune response regulationVSAvoidmolecular structure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and isolates only the essential functional element (MUC1 tandem repeat core peptide sequence) responsible for Siglec-binding and HMGB1 interaction, separating it from the full-length MUC1 protein. This extraction reduces molecular complexity while preserving the key immune regulatory function

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent divides the MUC1 protein into its functional core component (tandem repeat region with specific sequences) and combines it with Fc fragment. This segmentation creates a simplified modular structure that maintains immune regulatory capability while reducing overall molecular complexity

Inventive Principle:
Principle #1Segmentation

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 described compositions and methods effectively regulate immune responses, reduce immune-mediated tissue damage, and treat conditions such as inflammatory bowel diseases and arthritis by enhancing Siglec-binding and anti-inflammatory activities.

Implementation Method 1

glycosylated and/or sialylated core peptides

Methodology Applied
Scientific EffectGlycosylation:

Implementation Method 2

glycosylated and/or sialylated core peptides

Methodology Applied
Scientific EffectSialylation:

Implementation Method 3

bind to HMGB1

Methodology Applied
Scientific EffectMolecular binding: Adsorption

Implementation Method 4

enhancing Siglec-binding and anti-inflammatory activities

Methodology Applied
Scientific EffectSiglec-binding: Adsorption

Data Source

PatentUS20240336665A1Fusion proteins comprising 072 core peptide and use thereof
Publication Date: 2024.10.10 ACROIMMUNE GUANGZHOU BIOTECH LTD
  • US20240336665A1 patent drawing
  • US20240336665A1 patent drawing
  • US20240336665A1 patent drawing

AI summary

Provided are compositions of proteins based on fusion of one or more copy of the core peptide to the Fc fragment of human immunoglobulin and their use in treating diseases propagated by inflammations associated with tissue injuries.