Anti-CDH6 ADC and HIF-2α Inhibitor Combination for Synergistic Tumor Killing

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Solution Overview

Problem

Existing anti-CDH6 antibody-drug conjugates and HIF-2α inhibitors are used separately without known synergistic effects, necessitating a method to enhance antitumor activity through combined administration.

Innovation Solution

A specific anti-CDH6 antibody-drug conjugate and HIF-2α inhibitor are administered in combination, where the drug linker is conjugated to the antibody via a thioether bond, utilizing antibodies with defined CDR sequences and variable regions, and administered separately or in a single formulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If anti-CDH6 antibody-drug conjugate and HIF-2α inhibitor are used separately, then each agent can be administered with established dosing regimens, but the antitumor effect is limited compared to combination therapy

Engineering Contradiction:
Improveantitumor effectVSAvoidtreatment regimen complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines anti-CDH6 antibody-drug conjugate and HIF-2α inhibitor into a single pharmaceutical composition, merging two separate therapeutic agents with different mechanisms of action into one formulation. This allows simultaneous delivery of both agents, achieving synergistic antitumor effects while simplifying administration to a single combined treatment rather than separate regimens

Inventive Principle:
Principle #5Merging (Combining)

2Reliability

If combination therapy with multiple agents is used, then antitumor effect is enhanced through multiple mechanisms of action, but the treatment regimen becomes more complex

Engineering Contradiction:
Improveantitumor effectVSAvoidadministration convenience
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent merges multiple therapeutic agents into a single pharmaceutical composition that can be administered together, eliminating the need for separate administration of each agent. This maintains the benefits of combination therapy while significantly improving ease of operation and administration convenience

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The pharmaceutical composition serves multiple functions simultaneously: it delivers both anti-CDH6 antibody-drug conjugate and HIF-2α inhibitor, provides targeted therapy and hypoxia modulation in one formulation, and simplifies the treatment regimen into a single administrable unit with universal applicability

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentEP4691497A1Combination of Anti-CDH6 antibody-drug conjugate and HIF-2alpha inhibitor
Publication Date: 2026.02.11 DAIICHI SANKYO CO LTD
  • EP4691497A1 patent drawingFigure 1~5
  • EP4691497A1 patent drawingFigure 6~8
  • EP4691497A1 patent drawingFigure 9~10

AI summary

The present invention provides a pharmaceutical composition and a method of treatment, wherein a specific anti-CDH6 antibody-drug conjugate and an HIF-2α inhibitor are administered in combination. The present invention provides a pharmaceutical composition and a method of treatment, wherein an antibody-drug conjugate and an HIF-2α inhibitor are administered in combination, the antibody-drug conjugate being an antibody-drug conjugate in which a drug linker represented by the following formula (wherein A represents a connecting position to an anti-CDH6 antibody or a functional fragment of the antibody) and an anti-CDH6 antibody or a functional fragment of the antibody are conjugated via a thioether bond.