Anti-MUC16 Antibodies Targeting Retained Glycosylated Epitopes

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Solution Overview

Problem

Existing monoclonal antibodies targeting MUC16 in ovarian cancer primarily bind to the secreted CA-125 fraction, limiting their utility as therapeutic targets, as they do not effectively recognize the retained extracellular fraction (MUC-CD) of the antigen.

Innovation Solution

Development of antibodies and antigen-binding fragments that specifically target epitopes within the extracellular, non-shed form of MUC16, including glycosylation sites such as Asn1806, with defined complementarity determining regions (CDRs) to enhance binding and therapeutic potential.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If existing monoclonal antibodies are used to target MUC16, then they can bind to the secreted CA-125 fraction, but they fail to effectively recognize the retained extracellular fraction (MUC-CD) of the antigen

Engineering Contradiction:

Improveantibody binding specificityVSAvoidantibody target range

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The patent segments the MUC16 antigen recognition into two distinct parts: existing antibodies targeting the secreted CA-125 fraction, and newly developed antibodies (18C6, 10C6, 19C11, 7B12) targeting the retained MUC-CD fraction. This segmentation allows each antibody to specialize in recognizing its specific epitope without interference, resolving the contradiction between binding specificity and target range versatility.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Instead of trying to modify existing antibodies to recognize MUC-CD, the patent inverts the approach by generating entirely new antibodies that specifically target the retained fraction. This inversion strategy overcomes the limitation of existing antibodies by creating a complementary antibody pair rather than attempting to alter the original antibodies' specificity.

Inventive Principle:

Principle #13The other way round (Inversion)

2Quantity of substance

If most of the extracellular domain of MUC16 is cleaved and secreted, then CA-125 can be detected in serum, but the utility of MUC16 as a therapeutic target on ovarian carcinomas is limited

Engineering Contradiction:

ImproveCA-125 serum marker availabilityVSAvoidtherapeutic target reliability

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent uses the retained MUC-CD fraction as an intermediary target that bridges the gap between serum detection and therapeutic intervention. While the secreted CA-125 serves as a reliable biomarker for detection, the retained MUC-CD on tumor cells provides a reliable therapeutic target that is not subject to cleavage and secretion, thus resolving the contradiction between marker availability and target reliability.

Inventive Principle:

Principle #24Intermediary (Mediator)

3Reliability

If antibodies are developed to target the retained MUC-CD fraction, then therapeutic utility is improved, but the complexity of antibody generation and characterization increases

Engineering Contradiction:

Improvetherapeutic target reliabilityVSAvoidantibody development complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent performs preliminary action by generating and characterizing multiple antibody candidates (18C6, 10C6, 19C11, 7B12) against the retained MUC-CD fraction before selecting the most promising ones for further development. This preliminary screening and characterization process, while complex, establishes a robust foundation that simplifies subsequent therapeutic development by identifying proven effective antibodies early in the process.

Inventive Principle:

Principle #10Preliminary action

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

These antibodies effectively bind to the retained MUC16 fraction, inhibiting tumor invasion and growth, offering a new approach for diagnostic and therapeutic interventions in ovarian cancer.

Implementation Method 1

antibodies that immunospecifically bind to MUC16, a tethered mucin protein

Methodology Applied

Scientific EffectAntigen-antibody binding:

Implementation Method 2

the epitope includes an asparagine residue corresponding to Asn1806 or Asn1800 of the MUC16 sequence set forth in SEQ ID NO: 150 (and/or a glycosylated form(s) thereof); in some aspects, such one or more asparagine is glycosylated, such as N-glycosylated

Methodology Applied

Scientific EffectN-glycosylation:

Data Source

PatentUS12466894B2Anti-MUC16 antibodies and uses thereof

Publication Date: 2025.11.11 MEMORIAL SLOAN KETTERING CANCER CENT

AI summary

Provided herein are compositions, methods, and uses involving antibodies that immunospecifically bind glycosylated forms of MUC16, a tethered mucin protein. Also provided herein are uses and methods for managing, treating, or preventing disorders, such as cancer.