Fusion Proteins Target Autoreactive B Cells

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Solution Overview

Problem

Current treatments for autoimmune diseases, such as pemphigus vulgaris, often rely on immunosuppressive drugs that can have significant side effects and do not completely deplete autoreactive B cells, leading to potential relapse.

Innovation Solution

Development of fusion proteins that include a desmosomal cadherin or fragment thereof, combined with an effector-cell binding domain such as an Fc region or an antibody, to specifically target and deplete autoreactive B cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If immunosuppressive drugs are used to treat autoimmune diseases, then the immune response is suppressed, but side effects increase and complete depletion of autoreactive B cells is not achieved

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidside effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention segments the treatment approach by creating fusion proteins that specifically target only autoreactive B cells rather than suppressing the entire immune system. The fusion protein consists of an antigen-specific binding domain (targeting desmoglein for pemphigus) and an effector cell recruitment domain, enabling selective depletion of pathogenic B cells while preserving normal immune function.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The treatment applies local quality by making the immunosuppressive effect specific to certain B cells (autoreactive ones) rather than global immunosuppression. The fusion protein binds specifically to B cells expressing autoreactive BCRs through the antigen-specific domain, recruiting effector cells only to destroy these targeted cells, leaving other B cells and immune functions intact.

Inventive Principle:

Principle #3Local quality

2Reliability

If immunosuppressive drugs are used to treat autoimmune diseases, then immune suppression is achieved, but complete depletion of autoreactive B cells is not achieved leading to relapse

Engineering Contradiction:

Improvesustainability of treatmentVSAvoidtime to relapse

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The fusion protein performs preliminary action by directly engaging and depleting autoreactive B cells before they can produce pathogenic autoantibodies. By recruiting effector cells (NK cells, macrophages, or T cells) through the Fc region or effector cell binding domain, the treatment eliminates the source of autoantibodies proactively, preventing disease relapse.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The treatment incorporates feedback mechanisms where the fusion protein continuously binds to and depletes autoreactive B cells as long as they are present. The sustained presence of fusion protein in the system provides ongoing depletion pressure, preventing the rebound of autoreactive B cell populations that would lead to relapse.

Inventive Principle:

Principle #23Feedback

3Measurement precision

If fusion proteins are used to specifically target autoreactive B cells, then treatment precision is improved, but device complexity increases

Engineering Contradiction:

Improvespecificity of target cell depletionVSAvoidcomplexity of fusion protein structure

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The fusion protein is a composite molecule combining two functional domains: an antigen-specific binding domain (such as the extracellular domain of desmoglein for pemphigus vulgaris) and an effector cell recruitment domain (such as an Fc region or antibody fragment). This composite structure enables simultaneous specific antigen binding and effector cell engagement, achieving high precision with a single molecular entity rather than requiring complex multi-component systems.

Inventive Principle:

Principle #40Composite materials

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 fusion proteins effectively target and deplete autoreactive B cells, potentially offering a more precise and effective treatment for autoimmune diseases with reduced risk of relapse and side effects.

Implementation Method 1

the effector-cell binding domain can be an Fc portion of an antibody that can bind to an Fc receptor on an effector cell

Methodology Applied

Scientific EffectFc receptor binding:

Implementation Method 2

a domain including an autoreactive antigen from a diseased animal and a domain that can bind an effector cell

Methodology Applied

Scientific EffectAntigen-antibody binding:

Data Source

PatentUS20250129136A1Compositions and methods for treating disease

Publication Date: 2025.04.24 DANA FARBER CANCER INSTITUTE INC

AI summary

Aspects of the invention are drawn to compositions and methods for treating and preventing autoimmune disease.