HLA-Binding Peptide Sequences for HLA-A2 and HLA-A4 Affinity

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Solution Overview

Problem

Conventional HLA-binding peptides lack effective binding properties to HLA-A2 and HLA-A24 molecules, which are common in European and Japanese populations, limiting their potential in therapeutic applications.

Innovation Solution

Development of HLA-binding peptides with specific amino acid sequences, such as those listed in SEQ ID NOS: 1 to 80, that exhibit high-affinity binding to HLA-A type molecules, including those formed by deletion, substitution, or addition of one or two amino acid residues, and the use of DNA sequences and recombinant vectors to express these peptides.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional HLA-binding peptides are used, then they can bind to some HLA molecules, but they lack effective binding properties to HLA-A2 and HLA-A24 molecules which are common in European and Japanese populations

Engineering Contradiction:
Improvebinding effectiveness to HLA-A2 and HLA-A24 moleculesVSAvoidapplicability to different HLA types
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by systematically varying the amino acid sequence parameters of the peptide to optimize binding affinity to HLA-A2 and HLA-A24 molecules. Specific amino acid sequences (SEQ ID NOS: 1 to 80) were designed and tested to achieve high binding affinity (−log Kd value of 3 or greater) to these specific HLA types, resolving the contradiction between binding effectiveness and adaptability.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If HLA-binding peptides with high affinity to specific HLA types are designed, then binding affinity is improved, but the complexity of identifying and testing multiple sequences increases

Engineering Contradiction:
Improvebinding affinity to HLA-A type moleculesVSAvoidcomplexity of peptide sequence identification and testing
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by pre-designing and pre-testing a comprehensive set of candidate peptide sequences (SEQ ID NOS: 1 to 80) with predicted high binding affinity to HLA-A type molecules. This preliminary work identifies effective sequences before clinical application, reducing the complexity of subsequent identification and testing processes while ensuring high binding affinity.

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentUS8487076B1HLA-binding peptide, and DNA fragment and recombinant vector coding for said HLA-binding peptide
Publication Date: 2013.07.16 NEC CORP
  • US8487076B1 patent drawing

AI summary

There is provided an HLA-binding peptide binding to a HLA-A type molecule, the HLA-binding peptide comprising at least one type of amino acid sequence selected from the group consisting of SEQ ID NOS: 1 to 80, and consisting of not less than 8 and not more than 11 amino acid residues. All of these amino acid sequences herein mentioned are the predicted amino acid sequences binding to a human HLA-A type molecule with the prediction program using the certain active learning method.