Modified Peanut Extract for Allergy Immunotherapy
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Solution Overview
Problem
Current immunotherapy treatments for peanut allergy, particularly those using aqueous peanut extracts, often result in unacceptable systemic reactions, and modifying only major allergens like Ara h2 and Ara h6 may not be sufficient to treat peanut allergy effectively, as they do not account for all causative allergens.
Innovation Solution
A pharmaceutical composition comprising a modified whole peanut extract, achieved through reduction and alkylation of whole peanut extract, which breaks disulfide bonds and alters the secondary structure of proteins, thereby reducing IgE-binding and allergenicity, including major allergen Ara h1, which lacks disulfide bonds, and optionally incorporating aluminum to further reduce allergenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If aqueous peanut extract is used for immunotherapy, then treatment coverage is improved (all peanut allergens including Ara h1, Ara h2, and Ara h6), but systemic reactions increase (unacceptable safety profile)
Solution Approach 1:
The patent applies chemical modification by changing the molecular structure parameters of peanut allergens through reduction and alkylation. This breaks disulfide bonds in proteins like Ara h2 and Ara h6, and modifies the structure of Ara h1, thereby reducing their IgE-binding capacity and allergenicity while preserving immunogenicity for therapeutic desensitization
Solution Approach 2:
The patent converts the harmful allergenic properties of peanut proteins into beneficial therapeutic properties. By chemically modifying the allergens to reduce their ability to trigger IgE-mediated reactions while maintaining their ability to induce tolerance, the treatment transforms a harmful substance into a safe and effective immunotherapy agent
2Object-affected harmful factors
If only major allergens Ara h2 and Ara h6 are modified through reduction and alkylation, then IgE-binding is reduced for these specific allergens, but treatment effectiveness is insufficient (does not cover all peanut allergens)
Solution Approach 1:
The patent creates a universal modified peanut extract that addresses multiple allergens simultaneously. Rather than treating individual allergens separately, the modification approach is applied to the whole peanut extract, providing broad-spectrum coverage against Ara h1, Ara h2, Ara h6 and other peanut allergens with a single therapeutic formulation
3Object-affected harmful factors
If disulfide bonds in peanut proteins are broken through reduction and alkylation, then allergenicity is reduced for proteins containing disulfide bonds (Ara h2, Ara h6), but Ara h1 remains unaffected (lacks disulfide bonds)
Solution Approach 1:
The patent employs chemical modification parameters that affect different protein structures. The reduction and alkylation process targets disulfide bonds in proteins like Ara h2 and Ara h6, while separate modification mechanisms address Ara h1 which lacks disulfide bonds, ensuring comprehensive allergen modification across different protein structures
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 modified whole peanut extract significantly reduces IgE-binding and allergic reactions, making it suitable for therapeutic desensitization and prophylactic treatment of peanut allergy, as demonstrated by reduced anaphylactic responses in mouse models and increased IgG2a levels, indicating improved immune modulation.
Implementation Method 1
achieved through reduction and alkylation of whole peanut extract, which breaks disulfide bonds and alters the secondary structure of proteins
Implementation Method 2
achieved through reduction and alkylation of whole peanut extract, which breaks disulfide bonds and alters the secondary structure of proteins
Implementation Method 3
optionally incorporating aluminum to further reduce allergenicity
Data Source
AI summary
The present invention relates to compositions which can be used in immunotherapy and especially to compositions which can be used in immunotherapy for mammals, such as human mammals, suffering from peanut allergy. The present invention further relates to the use of the present compositions for the therapeutic treatment for desentizing the immune system of a mammal suffering from an allergy by immunotherapy and the use of the present compositions in a prophylactic treatment of a mammal with high predisposition to develop a certain allergy. Specifically, the present invention relates to pharmaceutical compositions comprising a modified whole peanut extract and pharmaceutically acceptable diluents and/or excipients, wherein said modified whole peanut extract is a reduced and subsequently alkylated whole peanut extract, preferably a whole defatted peanut extract comprising soluble peanut kernel proteins such as Ara h1, Ara h2 and Ara h6.