Multi-Specific Binding Proteins Targeting HER2 and NK Cells

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Solution Overview

Problem

Current cancer treatment options are not effective for all patients and can have substantial adverse side effects, highlighting the need for more specific and less cytotoxic therapies.

Innovation Solution

Development of multi-specific binding proteins that bind to NKG2D, CD16, and epidermal growth factor receptor 2 (HER2), facilitating the activation of natural killer cells to selectively target and kill cancer cells expressing HER2 without harming non-cancerous cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current cancer treatment options are used, then cancer cells can be targeted, but substantial adverse side effects occur and effectiveness varies

Engineering Contradiction:

ImproveeffectivenessVSAvoidadverse side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The therapeutic protein is segmented into distinct functional domains: an NKG2D-binding domain that engages natural killer cells, a HER2-binding domain that targets cancer cells, and a CD16-binding Fc region that enhances NK cell activation. This segmentation allows each domain to perform its specific function independently, achieving targeted cancer cell killing while minimizing off-target effects.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The multi-specific binding protein acts as an intermediary that bridges NK cells and HER2-positive cancer cells. By simultaneously binding to NKG2D on NK cells and HER2 on cancer cells, it facilitates direct interaction and cytotoxicity, while the CD16 binding provides an additional activation pathway. This intermediary mechanism enables precise targeting without affecting healthy cells.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If multi-specific binding proteins bind to NKG2D and CD16 on NK cells, then cytotoxicity against HER2-positive cancer cells is enhanced, but potential cytotoxicity to healthy cells expressing HER2 must be minimized

Engineering Contradiction:

Improvecytotoxicity against cancer cellsVSAvoidcytotoxicity to healthy cells

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The protein exhibits local quality differentiation through its domain architecture: the NKG2D-binding domain provides cancer-selective activation by engaging only on cancer cells expressing HER2, while the CD16-binding Fc region provides amplification of the cytotoxic response. This localized engagement ensures that cytotoxicity is directed specifically at HER2-positive cancer cells rather than healthy cells.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The therapeutic agent is a composite protein structure combining multiple binding functions in a single molecule. The composite nature integrates NKG2D binding, HER2 binding, and CD16 binding capabilities, creating a multi-functional therapeutic that achieves enhanced cancer cell killing through synergistic mechanisms while maintaining specificity.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS12275791B2Multi-specific binding proteins that bind HER2, NKG2D, and CD16, and methods of use

Publication Date: 2025.04.15 DRAGONFLY THERAPEUTICS INC

AI summary

Multi-specific binding proteins that bind to and kill human cancer cells expressing epidermal growth factor receptor 2 (HER2 or ErbB2), but does not kill non-cancerous healthy human cells expressing HER2 are described, as well as pharmaceutical compositions and therapeutic methods useful for the treatment of HER2 expressing cancer. The invention also relates to multi-specific binding proteins that trigger CD8+ T cell killing of tumor cells.