Genetically Modified B Cells for Sustained Therapeutic Agent Delivery

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Solution Overview

Problem

Current methods for treating chronic diseases and disorders, such as enzyme replacement therapy and gene therapy via viral vectors, face challenges including finite protein half-life, sub-optimal tissue penetration, localized toxicity, and limited dosing opportunities due to adverse reactions, making it difficult to achieve therapeutically effective levels of therapeutic agents in vivo.

Innovation Solution

Administering two or more sequential doses of genetically modified B cells engineered to produce therapeutic agents like IDUA, FIX, LPL, or LCAT, optimizing their migratory capacity and reducing inflammatory cytokine production to achieve long-term in vivo production and tissue distribution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If a single high dose of genetically modified B cells is administered to achieve therapeutically effective levels of therapeutic agent, then the therapeutic efficacy is improved, but the risk of adverse reactions and localized toxicity increases

Engineering Contradiction:

Improvetherapeutic agent dosageVSAvoidadverse reaction risk

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent divides the total therapeutic dosage into multiple sequential administrations of genetically modified B cells. Instead of delivering the entire therapeutic load in one injection, the treatment schedule spreads doses across multiple time points (e.g., days 0, 7, 14, 21), allowing the immune system to tolerate each individual dose while accumulating the desired therapeutic effect over time.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs preliminary administration of lower doses to prepare the immune system before delivering higher therapeutic doses. Early doses at lower levels serve as priming events that establish immune tolerance and create a favorable physiological environment for subsequent higher doses, reducing the shock and adverse reactions associated with large single-dose administrations.

Inventive Principle:

Principle #10Preliminary action

2Reliability

If viral vectors are used to deliver therapeutic genes, then the therapeutic agent can be produced in vivo, but the ability to administer multiple doses is limited due to immune reactions

Engineering Contradiction:

Improvein vivo production capabilityVSAvoiddosing flexibility

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent uses genetically modified B cells as living factories that continuously produce and secrete the therapeutic agent (such as alpha-iduronidase for MPS I) rather than relying on a single viral vector injection. These engineered B cells replicate and persist in the patient's body, providing ongoing production of the therapeutic protein, which can be supplemented with additional doses as needed without the limitations of viral vector re-administration.

Inventive Principle:

Principle #26Copying

3Quantity of substance

If therapeutic protein is injected directly, then the dosage can be controlled precisely, but the protein half-life is finite requiring frequent injections

Engineering Contradiction:

Improvetherapeutic agent dosage controlVSAvoidprotein half-life

Core Design Contradiction:

Quantity of substanceVSDuration of action of moving object

Solution Approach 1:

The genetically modified B cells function as autonomous therapeutic factories that continuously produce and secrete the therapeutic agent throughout their lifespan in the patient's body. Rather than requiring repeated external injections to maintain therapeutic levels, these self-sustaining cells provide ongoing production, effectively extending the duration of therapeutic action from hours or days to months or years, while maintaining dosage control through the initial engineering of the B cells.

Inventive Principle:

Principle #25Self-service

4Productivity

If endogenous tissues are altered to produce therapeutic agent via viral vectors, then the therapeutic agent is produced from a centralized location, but localized toxicity increases in the producing tissues

Engineering Contradiction:

Improvetherapeutic agent productionVSAvoidlocalized toxicity

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent engineers B cells with specific properties to produce the therapeutic agent in a controlled manner that avoids the localized toxicity problems of viral vector integration. The genetically modified B cells distribute therapeutic production across multiple circulating cells rather than concentrating it in a single transduced tissue site, and they can be directed to migrate to specific tissues needing treatment, thereby localizing the beneficial effect without the harmful concentrated toxicity of viral vector production sites.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20220193129A1B cells for in vivo delivery of therapeutic agents and dosages thereof

Publication Date: 2022.06.23 IMMUSOFT CORP

AI summary

The present invention relates to methods for administering autologous and/or allogeneic B cells genetically modified to produce a therapeutic agent, such as a therapeutic protein. Specifically disclosed are methods for administering a single, maximally effective dose of genetically modified B cells and for administering multiple doses of genetically modified B cells. The compositions and methods disclosed herein are useful for the long-term, in vivo delivery of a therapeutic agent.