Factor VIII Peptide Compound Sequesters Neutralizing Antibodies

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Solution Overview

Problem

Current treatments for hemophilia A, particularly those involving factor VIII replacement therapy, are compromised by the development of neutralizing antibodies, leading to increased morbidity and the need for higher dosages or immunosuppression, with existing methods for depleting undesirable antibodies being inefficient and not established in clinical practice.

Innovation Solution

A compound comprising a biopolymer scaffold and two peptides, each derived from factor VIII with specific amino acid fragments, is used to sequester or deplete antibodies against factor VIII, potentially reducing the titre of undesired antibodies and improving the efficacy and safety of factor VIII replacement therapy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If factor VIII replacement therapy is administered to treat hemophilia A, then the blood clotting function is improved, but neutralizing antibodies are developed against factor VIII

Engineering Contradiction:

Improveblood clotting functionVSAvoidneutralizing antibodies

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies the principle of converting harm into benefit by using the harmful neutralizing antibodies as targets for depletion. The compound specifically binds to and removes these antibodies from the patient's system, transforming the harmful immune response into a treatable condition. This resolves the contradiction by eliminating the harmful antibodies while preserving the beneficial clotting function of factor VIII.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent introduces a compound as an intermediary substance that mediates between the factor VIII replacement therapy and the patient's immune system. This compound selectively binds to neutralizing antibodies, facilitating their removal without interfering with the therapeutic action of factor VIII. The intermediary compound thus resolves the contradiction by providing a bridge that separates the harmful antibody effect from the beneficial clotting function.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If higher dosages of factor VIII are administered to overcome neutralizing antibodies, then the therapeutic efficacy is maintained, but the risk of inhibitor development and immunosuppression requirements increase

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidmorbidity and immunosuppression risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies the principle of extraction by specifically removing neutralizing antibodies from the patient's system using a selective depletion compound. This extraction approach allows maintenance of therapeutic efficacy at lower factor VIII dosages, as the harmful antibodies that would neutralize the therapy are actively removed. This resolves the contradiction by extracting the harmful element rather than compensating with higher doses.

Inventive Principle:

Principle #2Taking out (Extraction)

3Quantity of substance

If existing methods for depleting undesirable antibodies are used, then antibody titre reduction is achieved, but the methods are inefficient and not established in clinical practice

Engineering Contradiction:

Improveantibody titreVSAvoiddepletion efficiency

Core Design Contradiction:

Quantity of substanceVSProductivity

Solution Approach 1:

The patent applies parameter changes by developing a compound with optimized binding characteristics specifically tailored for neutralizing antibodies. The compound exhibits high affinity and selectivity for these antibodies, enabling efficient depletion with lower doses and fewer administrations compared to existing methods. This resolves the contradiction by changing the parameters of the depletion agent to achieve superior efficiency and clinical applicability.

Inventive Principle:

Principle #35Parameter changes

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 compound effectively reduces the titre of undesired antibodies, offering a selective and durable reduction, particularly effective in models of hemophilia A, both congenital and acquired, by specifically binding to and depleting factor VIII antibodies, thereby enhancing the effectiveness of factor VIII replacement therapy.

Implementation Method 1

A compound comprising a biopolymer scaffold and two peptides, each derived from factor VIII with specific amino acid fragments, is used to sequester or deplete antibodies against factor VIII

Methodology Applied

Scientific EffectAntibody binding: Absorption (physical)

Data Source

PatentUS20230365655A1Compound for increasing the efficacy of factor viii replacement therapy

Publication Date: 2023.11.16 ABLEVIA BIOTECH GMBH

AI summary

A compound for the sequestration of undesirable antibodies associated with hemophilia A, in particular when treated by factor VIII replacement therapy. The compound includes a biopolymer scaffold and at least two peptides derived from factor VIII with a sequence length of 6-13 amino acid, wherein each of the peptides independently includes a 6-amino-acid fragment of the amino-acid sequence of factor VIII, optionally wherein at most three, preferably at most two, more preferably at most one amino acid is independently substituted by any other amino acid. Also provided are pharmaceutical compositions including the compound, as well as methods for treating hemophilia A.