Bispecific MUC16-CD3 Antibodies for Targeted T Cell Tumor Killing

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Solution Overview

Problem

Current therapies targeting MUC16, such as Oregovomab and abgovomab, have limited success in treating cancers like ovarian cancer, and there is a need for more effective methods to specifically target and kill MUC16-expressing cells while activating T cells for immune response.

Innovation Solution

Development of antibodies and bispecific antigen-binding molecules that bind to MUC16 and CD3, allowing for targeted T cell activation and killing of MUC16-expressing cells, including ovarian tumor cells, through antibody-drug conjugates and bispecific antibodies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional anti-MUC16 antibodies (Oregovomab, abgovomab) are used to target MUC16-expressing cells, then MUC16 targeting is achieved, but therapeutic efficacy is limited

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidimmune activation capability

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines MUC16 targeting capability with T cell activation capability into a single bispecific antibody molecule. The antibody has a first antigen-binding domain that specifically binds MUC16 and a second antigen-binding domain that specifically binds CD3, merging the functions of target recognition and immune activation that were previously separate mechanisms

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The bispecific antibody serves multiple functions simultaneously: it targets MUC16-expressing cells through its first antigen-binding domain, activates T cells through its second antigen-binding domain that binds CD3, and bridges T cells to tumor cells to enable directed cytotoxicity. This multi-functionality overcomes the limitation of conventional single-function antibodies

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If T cell activation is enhanced through anti-CD3 antibodies, then immune response is strengthened, but specificity for target cells is reduced

Engineering Contradiction:

Improveimmune response strengthVSAvoidtargeting specificity

Core Design Contradiction:

ReliabilityVSMeasurement precision

Solution Approach 1:

The bispecific antibody creates a localized interaction where T cell activation via CD3 binding occurs specifically at the interface between the antibody and T cells, while MUC16 binding occurs locally at the tumor cell surface. This spatial localization ensures that immune activation is confined to the vicinity of target cells, providing both strong immune response and high specificity

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The bispecific antibody acts as an intermediary molecule that bridges T cells and MUC16-expressing cells. By simultaneously binding CD3 on T cells and MUC16 on tumor cells, it directs the immune response specifically to target cells while maintaining strong T cell activation, thus resolving the contradiction between response strength and specificity

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If bisspecific antibodies binding MUC16 and CD3 are developed, then T cell-mediated killing of MUC16 cells is enhanced, but molecular complexity increases

Engineering Contradiction:

Improvetargeted cell killing efficiencyVSAvoidantibody molecular structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The bisspecific antibody is constructed by segmenting two separate antibody functions into distinct antigen-binding domains within a single molecular framework. The first antigen-binding domain targets MUC16 while the second antigen-binding domain targets CD3, allowing independent optimization of each binding function while maintaining overall molecular integrity and manufacturability

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS12570764B2Anti-MUC16 antibodies, antibody-drug conjugates, and bispecific antigen-binding molecules that bind MUC16 and CD3, and uses thereof

Publication Date: 2026.03.10 REGENERON PHARMACEUTICALS INC

AI summary

Mucin 16 (MUC16) is highly expressed in ovarian cancer and expression on cancer cells is shown to protect tumor cells from the immune system. The present invention provides novel full-length human IgG antibodies that bind to human and MUC16 (monospecific antibodies). The present invention also provides novel bispecific antibodies (bsAbs) that bind to both MUC16 and CD3 and activate T cells via the CD3 complex in the presence of MUC16-expressing tumors. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human and monkey CD3, and a second antigen-binding molecule that specifically binds human and monkey MUC16. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing MUC16. The bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced MUC16-targeted immune response is desired and/or therapeutically beneficial. For example, the bispecific antibodies of the invention are useful for the treatment of various cancers, including ovarian cancer. The present invention also includes anti-MUC16 antibody drug conjugates which inhibit tumor growth in vivo. In some embodiments, the anti-MUC16 antibodies are useful in diagnostic methods for identifying the presence of MUC16 in tissue and/or plasma samples.