Anti-Müllerian Inhibiting Substance Antibodies for MIS Signaling Blockade

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Solution Overview

Problem

Current therapies targeting the MIS/MISRII signaling pathway in cancers like ovarian carcinoma face challenges due to difficulties in producing sufficient bioactive MIS and delivering it to the tumor site, and recombinant MIS antibodies like murlentamab show limited efficacy through mechanisms unrelated to the MIS signaling pathway.

Innovation Solution

Development of anti-MIS antibodies, specifically the B10 antibody and its variants, which target ALK2 and ALK3 receptors to inhibit MIS signaling, using MIS siRNAs to suppress proliferative effects in ovarian cancer cells, offering an innovative therapeutic approach.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If recombinant MIS is used to target the MIS/MISRII signaling pathway, then therapeutic effect is improved, but production difficulty and delivery challenge worsen

Engineering Contradiction:

Improvetherapeutic effectVSAvoidproduction difficulty

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses anti-MISRII antibodies as intermediary molecules to block the MIS/MISRII signaling pathway. Instead of administering MIS directly (which faces production and delivery challenges), the antibodies bind to MISRII receptors on tumor cells, preventing MIS from activating the pathway, thereby achieving therapeutic effect without the manufacturing difficulties of producing bioactive MIS

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the direct hormonal therapy approach (using MIS) with an immunotherapy approach (using antibodies). This substitution transforms the therapeutic mechanism from replacing a difficult-to-produce hormone with a more easily manufacturable antibody product that can be administered to block the signaling pathway

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Ease of operation

If anti-MISRII antibodies like murlentamab are used, then delivery to tumor site is improved, but mechanism of action becomes unrelated to MIS signaling pathway

Engineering Contradiction:

Improvedelivery to tumor siteVSAvoidmechanism of action relevance

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

Instead of using antibodies that activate the MIS pathway (like murlentamab which works through ADCC and ADCP), the patent employs antibodies that block the pathway by binding to MISRII receptors. This inverted approach directly targets the signaling pathway mechanism, ensuring that the antibody's action is fundamentally linked to preventing MIS signaling rather than relying on indirect cytotoxic mechanisms

Inventive Principle:

Principle #13The other way round (Inversion)

3Object-affected harmful factors

If high doses of MIS are administered to induce apoptosis, then cancer cell death is improved, but proliferative effect suppression is worsened

Engineering Contradiction:

Improvecancer cell deathVSAvoidproliferative effect suppression

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent changes the parameter of MIS concentration from high doses (which induce apoptosis) to low concentrations (which suppress proliferation). By using anti-MISRII antibodies to block the pathway, the system achieves proliferative suppression without requiring high MIS doses, thereby avoiding the unwanted apoptotic effects while maintaining therapeutic benefit

Inventive Principle:

Principle #35Parameter changes

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 anti-MIS antibodies effectively inhibit cancer cell viability and clonogenic survival, providing a novel method to suppress MIS proliferative effects without inducing apoptosis.

Implementation Method 1

the anti-MIS antibody B10... target ALK2 and ALK3 receivers to inhibit MIS signaling

Methodology Applied

Scientific EffectAntibody binding:

Implementation Method 2

using MIS siRNAs to suppress proliferative effects in ovarian cancer cells

Methodology Applied

Scientific EffectRNA interference:

Data Source

PatentUS12441788B2Anti-müllerian inhibiting substance antibodies and uses thereof

Publication Date: 2025.10.14 INST NAT DE LA SANTE & DE LA RECHERCHE MEDICALE (INSERM)

AI summary

In ovarian carcinoma, Müllerian Inhibiting Substance (MIS) type II receptor (MISRII) and the MIS/MISRII signaling pathway are potential therapeutic targets. Conversely, the role of the three MIS type I receptors (MISRI; ALK2, ALK3 and ALK6) in this cancer needs to be clarified. Using four ovarian cancer cell lines and ovarian cancer cells isolated from patients' tumor ascites, the inventors found that ALK2 and ALK3 are the two main MISRIs involved in MIS signaling at low and high MIS concentrations, respectively. Moreover, high MIS concentrations were associated with apoptosis and decreased clonogenic survival, whereas low MIS concentrations improved cancer cell viability. Finally, the inventors showed that anti-MIS antibody B10 inhibited MIS pro-survival effect. These last results open the way to an innovative therapeutic approach to suppress MIS proliferative effect, instead of administering high doses of MIS to induce cancer cell apoptosis.