Multimeric Anti-CD38/Anti-CD3 Antibodies for B Cell Depletion

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current treatments for autoimmune disorders, such as rituximab and other immunosuppressive agents, fail to effectively deplete B cells in secondary lymphoid organs, limiting their efficacy, and there is a need for improved therapies that can reduce immune cell populations with minimal toxicity.

Innovation Solution

Administration of a multimeric bispecific anti-CD38/anti-CD3 antibody comprising five bivalent binding units and a modified J chain, where each binding unit includes IgM heavy and light chains with specific complementarity determining regions, and an scFv molecule that binds to CD3, to target and reduce CD38-expressing cells contributing to autoimmune disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If rituximab is used to treat autoimmune disorders, then B cell reduction occurs, but depletion in secondary lymphoid organs is insufficient

Engineering Contradiction:

ImproveB cell populationVSAvoideffectiveness

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent combines two antibody specificities (anti-CD38 and anti-CD3) into a single bispecific antibody molecule, enabling simultaneous targeting of B cells (via CD38) and T cell engagement (via CD3). This merging of functions allows the antibody to not only deplete B cells but also enhance their elimination through T cell-mediated cytotoxicity, thereby improving effectiveness in secondary lymphoid organs where rituximab alone fails

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The bispecific antibody performs multiple functions: it binds to CD38 on B cells for targeting, engages CD3 on T cells for immune activation, and utilizes the multimeric structure (IgM or IgA based) to provide both depletion and immune modulation capabilities. This multi-functionality addresses the insufficiency of rituximab by adding T cell engagement and enhanced cytotoxicity while maintaining B cell reduction

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Object-affected harmful factors

If immunosuppressive agents are used to treat autoimmune disorders, then immune response is reduced, but toxicity increases

Engineering Contradiction:

Improveimmune responseVSAvoidtoxicity

Core Design Contradiction:

Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

Instead of using broad immunosuppression that suppresses all immune activity (causing toxicity), the patent inverts the approach by using a targeted antibody that selectively engages CD3 on T cells to induce apoptosis of activated T cells and B cells. This inverted strategy replaces non-specific immunosuppression with specific immune redirection, reducing toxicity while maintaining effectiveness

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent converts the potentially harmful effect of T cell activation (which can contribute to autoimmune pathology) into a beneficial therapeutic mechanism. By engineering the bispecific antibody to engage CD3, the activated T cells are redirected to kill pathogenic B cells and plasma cells through cytotoxicity. The harmful T cell activation is thus transformed into a beneficial anti-autoimmune mechanism, reducing toxicity associated with broad immunosuppression

Inventive Principle:

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

3Quantity of substance

If multimeric bispecific antibody is used to target CD38-expressing cells, then cell reduction efficacy improves, but treatment complexity increases

Engineering Contradiction:

ImproveCD38-expressing cell populationVSAvoidantibody structure

Core Design Contradiction:

Quantity of substanceVSDevice complexity

Solution Approach 1:

The patent utilizes the natural segmentation of antibody structures (heavy chains, light chains, constant regions, variable regions) to create the bispecific format. By dividing the antibody into modular components with specific functions (CD38 binding, CD3 binding, multimerization capability), the complex functionality is achieved through systematic assembly of standardized segments, making the complexity manageable and manufacturable

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs parameter changes in the antibody structure, specifically using different isotype frameworks (IgM or IgA) and controlling multimerization states (pentameric IgM or dimeric/tetrameric IgA). These parameter changes allow optimization of the balance between efficacy (through multivalency and T cell engagement) and manufacturability, as well as different pharmacokinetic profiles for various administration routes

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20260070999A1Methods of treating autoimmune disorders using multimeric Anti-CD38/Anti-CD3 antibodies

Publication Date: 2026.03.12 IGM BIOSCIENCES INC

AI summary

This disclosure provides methods of treating an autoimmune disorder comprising administering to a subject in need of treatment an effective amount of a multimeric bispecific anti-CD38/anti-CD3 antibody comprising five bivalent binding units and a modified J chain. For example, the autoimmune disorder is, in some embodiments, a disorder wherein CD38-expressing cells contribute to chronic inflammation in the subject.