IdeS Polypeptide Cleavage of Pathogenic IgG Antibodies
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Solution Overview
Problem
Current treatments for diseases mediated by IgG antibodies, such as autoimmune diseases and transplant rejection, are inadequate in effectively preventing or treating these conditions.
Innovation Solution
The use of the IdeS polypeptide or its encoding polynucleotide, which specifically degrades IgG antibodies by cleaving them into Fc and Fab fragments, thereby inhibiting their pathogenic activity, is administered to prevent or treat diseases mediated by IgG antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for IgG-mediated diseases are used, then disease management is attempted, but they are inadequate in effectively preventing or treating these conditions
Solution Approach 1:
The patent extracts and eliminates the pathogenic IgG antibodies from the system by using IdeS enzyme to specifically cleave IgG into inactive Fab and Fc fragments. This removes the harmful component (pathogenic IgG) while preserving other immune functions, directly addressing the inadequacy of current treatments for IgG-mediated diseases
Solution Approach 2:
The invention changes the molecular structure parameter of IgG antibodies by catalyzing proteolytic cleavage at the hinge region, transforming intact IgG into Fab and Fc fragments. This structural parameter change eliminates pathogenic activity while maintaining therapeutic potential through targeted modification of the antibody molecule
2Reliability
If IdeS is administered to treat rheumatoid arthritis, then complete prevention of disease development is achieved, but potential toxicity concerns arise
Solution Approach 1:
The patent applies local quality by using IdeS with extraordinarily high substrate specificity that acts only on IgG antibodies and not on other proteins or tissues. This localized action at the molecular level (specific to IgG hinge region) provides complete preventive efficacy while avoiding broad toxic effects on other physiological systems
Solution Approach 2:
The invention converts the potentially harmful pathogenic IgG antibodies into beneficial or neutral components by cleaving them into Fab and Fc fragments. The Fab fragments lose pathogenicity while the Fc fragments can be cleared safely, transforming the harmful substance into harmless or potentially beneficial components
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
IdeS effectively prevents the development of rheumatoid arthritis in mice with no observable toxic effects and demonstrates potent, local therapeutic effects, suggesting its potential in treating various conditions mediated by IgG antibodies.
Implementation Method 1
IdeS catalyses a single proteolytic cleavage in the lower hinge region of human IgG. This proteolytic degradation promotes inhibition of opsonophagocytosis and interferes with the killing of group A Streptococcus.
Data Source
AI summary
The invention provides use of an IdeS polypeptide, or a polynucleotide encoding an IdeS polypeptide, in the manufacture of a medicament for the treatment or prevention of a disease or condition mediated by IgG antibodies.