Combination Therapy Targeting CSF-1R and PD-L1 Pathways

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Solution Overview

Problem

Current cancer treatments are inadequate in targeting CSF-1R and PD-L1 pathways effectively, leading to limited therapeutic options for cancers characterized by immune cell infiltrates and overexpression of CSF-1R ligands, which promote tumor progression and immune evasion.

Innovation Solution

A combination therapy using specific antibodies that bind to human CSF-1R and PD-L1, characterized by specific heavy and light chain variable domains, administered together to target CSF-1R expressing tumors and modulate immune responses, thereby inhibiting ligand-independent signaling and enhancing antiproliferative activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current cancer treatments are used, then treatment options are limited, but therapeutic effectiveness is insufficient

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidtreatment options

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines two different antibody therapies targeting distinct pathways: anti-CSF-1R antibodies that block macrophage recruitment and survival, and anti-PD-L1 antibodies that release immune checkpoints. This combination approach merges two mechanisms of action to achieve synergistic antitumor effects, overcoming the limitations of single-agent therapies and providing both increased effectiveness and expanded treatment options.

Inventive Principle:

Principle #5Merging (Combining)

2Productivity

If CSF-1R ligands are overexpressed, then tumor progression is promoted, but immune cell infiltrates increase

Engineering Contradiction:

Improvetumor progressionVSAvoidimmune cell infiltrates

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The patent exploits the paradoxical situation where CSF-1R ligand overexpression both promotes tumor progression and recruits immune cells. By targeting CSF-1R with specific antibodies, the therapy converts the harmful effect (enhanced tumor growth through ligand overexpression) into a beneficial opportunity (increased immune cell presence that can be activated by combined PD-L1 blockade) to achieve antitumor immunity.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Reliability

If antibodies against CSF-1R are used, then macrophage recruitment is inhibited, but ligand-independent signaling may persist

Engineering Contradiction:

Improvemacrophage recruitment inhibitionVSAvoidligand-independent signaling

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent introduces a second intermediary agent (anti-PD-L1 antibody) to work in conjunction with the anti-CSF-1R antibody. While the anti-CSF-1R antibody blocks CSF-1R-mediated macrophage recruitment, the anti-PD-L1 antibody mediates immune activation to counteract any residual ligand-independent signaling effects, providing a dual-layer approach that addresses both the primary and potential alternative pathways.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentEP3044235B1Combination therapy of antibodies against human CSF-1r and antibodies against human PD-l1

Publication Date: 2020.09.02 F HOFFMANN LA ROCHE & CO AG

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AI summary

The present invention relates to the combination therapy of specific antibodies which bind human CSF-1R with specific antibodies which bind human PD-L1.