AAV Capsid Protein I-453 Insertion for Targeted Gene Therapy

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Solution Overview

Problem

Current monoclonal antibody therapies face limitations due to immune responses against therapeutic antibodies, requiring immunosuppression and frequent administration, while anti-idiotypic antibody therapies struggle with low antibody titers and technical difficulties in generating specific vaccines, and existing viral vectors like papillomavirus have manufacturing challenges and immunogenicity issues.

Innovation Solution

Development of a structural protein of adeno-associated virus (AAV) with an amino acid insertion at position I-453, allowing for the display of peptides on the viral capsid surface, which can mediate transduction and immune response without interfering with heparin sulfate proteoglycan binding, enabling targeted gene therapy and vaccination.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If monoclonal antibody therapies are used, then specific antigen recognition is achieved, but immune response against the antibody limits efficacy

Engineering Contradiction:

Improveantigen recognition specificityVSAvoidtherapeutic efficacy

Core Design Contradiction:

Measurement precisionVSReliability

Solution Approach 1:

Instead of using monoclonal antibodies that directly recognize the target antigen (which provoke anti-idiotypic responses), the patent uses anti-idiotypic antibodies that recognize the idiotype of the therapeutic antibody. This inverted approach leverages the patient's own immune response mechanism to generate therapeutic effect, turning the harmful anti-idiotype response into a beneficial therapeutic mechanism.

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The anti-idiotypic antibody serves as an intermediary that indirectly targets the original antigen. By recognizing the idiotype of the monoclonal antibody, the anti-idiotypic antibody activates the patient's immune system to produce polyclonal antibodies against the target antigen, thus mediating the therapeutic effect without direct antibody-antigen interaction.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If monoclonal antibody therapies are administered, then therapeutic effect is achieved, but frequent administration is required

Engineering Contradiction:

Improvetherapeutic effectVSAvoidadministration frequency

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The anti-idiotypic antibody vaccination enables the patient's immune system to produce and maintain its own therapeutic antibodies. The vaccine induces long-lasting immunological memory, allowing the patient's immune system to self-sustain the therapeutic response without requiring frequent external antibody administrations.

Inventive Principle:

Principle #25Self-service

3Reliability

If anti-idiotypic antibody therapies are used, then active immune response is induced, but antibody titers are insufficient

Engineering Contradiction:

Improveimmune response activationVSAvoidantibody titer

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent modifies the anti-idiotypic antibody structure by inserting amino acids at specific positions (I-453, I-587) to optimize its immunogenicity and functional properties. These structural parameter changes enhance the ability of the anti-idiotypic antibody to stimulate polyclonal antibody production, thereby increasing achievable antibody titers.

Inventive Principle:

Principle #35Parameter changes

4Measurement precision

If papillomavirus vectors are used, then antigen presentation is achieved, but manufacturing complexity increases

Engineering Contradiction:

Improveantigen presentation capabilityVSAvoidviral vector production

Core Design Contradiction:

Measurement precisionVSEase of manufacture

Solution Approach 1:

Instead of using entire papillomavirus particles that require complex assembly and purification, the patent focuses on specific local regions of the virus structure - namely the L1 protein capsid proteins - that are sufficient for antigen presentation. This localized approach simplifies manufacturing by working with individual protein components rather than complete viral particles.

Inventive Principle:

Principle #3Local quality

5Reliability

If papillomavirus vectors are used, then immune response is generated, but immunogenicity issues arise

Engineering Contradiction:

Improveimmune response generationVSAvoidviral immunogenicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and utilizes only the essential functional elements of the papillomavirus - the L1 capsid proteins capable of forming virus-like particles for antigen presentation - while excluding the problematic viral genome and other viral components that cause harmful immunogenicity. This extraction approach retains the beneficial antigen presentation capability while eliminating the harmful viral immunogenicity.

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS10822378B2Mutated structural protein of a parvovirus

Publication Date: 2020.11.03 MEDIGENE AG

AI summary

The present invention is related to a structural protein of a parvovirus with an amino acid insertion at the insertion site I-453, a library comprising the protein, a multimeric structure comprising the protein, a nucleic acid encoding the protein, a vector, virus or cell comprising the nucleic acid, a process for the preparation of the protein, a medicament comprising the protein, nucleic acid or multimeric structure as well as methods and uses involving the protein, nucleic acid or multimeric structure.