Dual-Target DVD-Ig Conjugates for Broader Prostate Tumor Coverage

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Solution Overview

Problem

Current therapies for metastatic prostate cancer are limited, and there is a need for novel therapeutics that can effectively target prostate cancer antigens like PSMA and STEAP1 to enhance tumor coverage, mitigate resistance, and drive durable responses.

Innovation Solution

Development of dual-variable domain immunoglobulin (DVD-Ig) drug conjugates that bind to both human STEAP1 and human PSMA, utilizing a symmetrical molecule structure with identical heavy and light chains, and are conjugated with cytotoxic drugs like Topoisomerase 1 Inhibitors (TOP1i) to enhance tumor targeting and cell killing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If monospecific ADCs are used to target prostate cancer antigens, then tumor targeting is achieved, but tumor coverage is limited and resistance develops

Engineering Contradiction:

Improvetumor coverageVSAvoidresistance mitigation

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The DVD-Ig molecule is designed to bind both PSMA and STEAP1 antigens simultaneously, enabling a single therapeutic agent to target multiple tumor-associated antigens. This multi-functionality approach allows the ADC to cover broader tumor populations and mitigate resistance mechanisms that arise from single-antigen targeting, directly resolving the contradiction between limited tumor coverage and resistance development

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Adaptability or versatility

If dual-targeting DVD-Ig is used to enhance tumor coverage, then broader efficacy is achieved, but molecular complexity increases

Engineering Contradiction:

Improvetumor coverageVSAvoidmolecular structure

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent merges two monoclonal antibody specificities into a single DVD-Ig molecular framework. By combining the variable domains of anti-PSMA and anti-STEAP1 antibodies into one symmetrical molecule structure, the invention achieves dual-targeting capability while maintaining a unified, manageable molecular architecture that facilitates production and clinical development

Inventive Principle:

Principle #5Merging (Combining)

3Strength

If ADCs with high cytotoxic payload are used to kill tumor cells, then cell killing efficacy is improved, but toxicity to normal tissues increases

Engineering Contradiction:

Improvecell killing efficacyVSAvoidsystemic toxicity

Core Design Contradiction:

StrengthVSObject-affected harmful factors

Solution Approach 1:

The therapeutic system is segmented into three distinct functional components: the DVD-Ig targeting moiety that provides dual-antigen binding specificity, the cytotoxic payload that delivers cell-killing activity, and the linker that connects them. This segmentation allows the highly potent cytotoxic agent to be delivered selectively to tumor cells through dual-targeting, maximizing efficacy while minimizing systemic exposure and toxicity to normal tissues

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20260091121A2PSMA-STEAP1 DUAL VARIABLE DOMAIN IMMUNOGLOBULIN (DVD-Ig) MOLECULES AND DRUG CONJUGATES

Publication Date: 2026.04.02 ABBVIE INC

AI summary

The present disclosure provides dual variable domain immunoglobulin (DVD-Ig) molecules that bind to human STEAP1 and human PSMA and their drug conjugates, and methods of using the same.