Peptide Combinations for Grass Allergy Immunotherapy
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Solution Overview
Problem
Current grass allergen-specific immunotherapies face challenges in providing broad coverage across different MHC Class II alleles worldwide, leading to limited effectiveness and safety concerns due to the need for multiple peptides and extensive clinical development, while peptide-based immunotherapies require a combination of peptides to address a wide population, increasing costs and complexity.
Innovation Solution
A composition of four to six peptides, specifically selected to cover a high fraction of the HLA Class II allele repertoire, ensuring broad immunological potency and cross-reactivity, with a focus on solubility, stability, and reduced risk of IgE-mediated adverse events, allowing for a more efficient and safer treatment regimen.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If multiple peptides are used to cover broad MHC Class II alleles, then population coverage is improved, but device complexity and manufacturing cost increase
Solution Approach 1:
The patent applies universality by designing a peptide combination that can bind to multiple MHC Class II alleles (including DRB1*01:01, DRB1*03:01, DRB1*04:01, and others) through a single formulation. The selected peptides have been engineered to recognize conserved regions across different HLA molecules, allowing one peptide mix to serve multiple population groups simultaneously, thereby achieving broad adaptability without proportionally increasing complexity
Solution Approach 2:
The patent employs parameter changes by modifying peptide sequences to optimize their binding affinity across different MHC Class II alleles. Specific amino acid residues in the peptides are selected or modified to match conserved binding pockets in diverse HLA molecules, changing the molecular parameters of peptide structure to achieve broader coverage while maintaining a manageable number of peptides in the combination
2Reliability
If extensive clinical development is conducted to ensure safety and efficacy, then reliability is improved, but loss of time and development cost increase
Solution Approach 1:
The patent applies preliminary action by conducting extensive in silico screenings and in vitro validations before clinical trials. The peptide combinations are pre-tested for binding affinity to multiple MHC Class II alleles, immunogenicity predictions, and cross-reactivity assessments using computational models and cell-based assays. This preliminary characterization reduces the need for extensive iterative clinical testing, thereby improving reliability while reducing development time
Solution Approach 2:
The patent uses copying by leveraging existing validated peptide sequences from previously characterized allergens and applying them to new peptide combinations. Rather than developing entirely new peptides from scratch, the invention copies and adapts proven immunogenic sequences, using established structural and functional data to guide the design of new peptide mixes, thus reducing development time while maintaining reliability
3Object-affected harmful factors
If peptide immunotherapy is used instead of whole allergen, then safety is improved, but manufacturing precision requirements increase
Solution Approach 1:
The patent applies segmentation by dividing the complex allergen protein into smaller, discrete peptide fragments (typically 15-30 amino acids each). These segmented peptides retain the critical T-cell epitopes while removing the problematic B-cell epitopes and other components that cause IgE-mediated adverse reactions. The segmentation approach inherently improves safety by isolating only the necessary immunogenic portions
Solution Approach 2:
The patent employs parameter changes by precisely controlling peptide physical and chemical parameters during manufacturing, including purity (>95%), specific activity, amino acid sequence accuracy, and absence of aggregation. These stringent parameter specifications ensure that the segmented peptides maintain their intended immunological function while minimizing off-target effects, thereby managing manufacturing precision requirements through defined quality parameters
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 peptide composition achieves high T cell response coverage in a diverse population, even at low doses, with improved safety and stability, potentially offering a more effective and widely applicable treatment for grass allergies with reduced clinical development burdens.
Implementation Method 1
peptides are bound by Human Leucocyte Antigen (HLA)MHC (Major histocompatibility Complex) class II molecules (referred to as HLA at gene level) on the surface of Antigen Presenting Cells (APC) which present the peptides for CD4+ T cell surveillance
Data Source
AI summary
The invention relates to combinations of peptides derived from a portion of an amino sequence of a grass pollen allergen, e.g. the allergens Phl p 1, Phl p 2, Phl p 3, Phl p 4 and/or Phl p 5, or a peptide variant thereof. Such peptides comprise at least one T cell epitope mid a high number of patients in a worldwide population will have HLA Class II alleles with the potential to bind the peptides of the peptide combinations. The invention also relates to the use of such peptide combinations in relieving an immune response caused by grass pollen species.