B7 Ligand Peptide Mimetics Block Superantigen Receptor Binding

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Solution Overview

Problem

Current treatments for bacterial infections and toxic shock induced by Gram-positive and Gram-negative bacteria are inadequate in preventing excessive inflammatory cytokine responses, which can lead to severe outcomes such as sepsis and death, as existing therapies fail to effectively block the interaction between superantigens and their receptors on T cells.

Innovation Solution

Development of isolated and purified peptides mimicking the dimer interface of B7-2 and B7-1, which compete with superantigens for binding to CD28 and B7-2, thereby inhibiting the induction of inflammatory cytokines and providing protection against lethal superantigen challenges.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If existing therapies are used to treat bacterial infections, then bacterial growth may be controlled, but excessive inflammatory cytokine responses cannot be prevented

Engineering Contradiction:

Improveinflammatory cytokine responseVSAvoidprotection against sepsis and toxic shock

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent uses peptide mimetics as intermediary substances that bind to superantigens and prevent their interaction with T-cell receptors. These peptide intermediaries compete with the natural binding interface, effectively blocking the harmful signaling pathway without requiring direct modification of the superantigen or the receptor

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates simplified copies (peptide mimetics) of the critical binding interface region of B7 ligands. These peptide copies replicate the essential binding properties of the full-length protein interface, allowing them to effectively compete with superantigens for binding to CD28 and CTLA-4 receptors

Inventive Principle:

Principle #26Copying

2Object-affected harmful factors

If peptide mimetics are designed to block superantigen binding, then inflammatory response is reduced, but the complexity of identifying effective peptide sequences increases

Engineering Contradiction:

Improvesuperantigen-receptor interactionVSAvoidpeptide sequence identification and optimization

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent segments the complex B7 ligand structure into smaller, functionally critical peptide fragments corresponding to the dimer interface region. By focusing only on this essential segment (residues involved in dimerization and superantigen binding), the invention simplifies the design process while maintaining blocking effectiveness

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The invention applies local quality by concentrating the blocking function in a specific local region (the dimer interface peptide sequence) rather than requiring modification of the entire B7 ligand structure. This localized approach identifies critical residues that are sufficient for binding competition

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS11613565B2Isolated peptides derived from the B7 ligand dimer interface and uses thereof

Publication Date: 2023.03.28 YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD

AI summary

Disclosed are peptides comprising amino acid residues of the dimer interface of human B7-1 and B7-2 and compositions and uses thereof.