Multispecific Antibody Target Molecule Internalization

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Solution Overview

Problem

Current strategies for reducing the concentration of target molecules in therapeutic settings often involve genetic and nucleic acid-based approaches, which are fraught with technical complications and unintended side effects.

Innovation Solution

The development of multispecific antigen-binding molecules that simultaneously bind a target molecule and an internalizing effector protein, facilitating the physical linkage and subsequent internalization and degradation of the target molecule.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If genetic and nucleic acid-based strategies are used to reduce target molecule concentration, then the amount of target molecule can be reduced, but technical complications and unintended side effects increase

Engineering Contradiction:

Improvetarget molecule concentrationVSAvoidtherapeutic safety

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent uses an internalizing effector protein as an intermediary to achieve target molecule reduction. Instead of directly using genetic/nucleic acid strategies that cause side effects, the effector protein mediates the process by binding to the target molecule and facilitating its internalization and degradation through cellular machinery, thereby reducing target concentration while avoiding the complications of direct genetic approaches

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the mechanical/genetic system (direct genetic modification or nucleic acid-based approaches) with a protein-based biological system. The multispecific antigen-binding molecule and internalizing effector protein work together through protein-protein interactions to achieve target reduction, substituting the problematic genetic mechanism with a more controllable protein-based mechanism that avoids unintended side effects

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Quantity of substance

If blocking interaction between cytokine and receptor is used to attenuate cellular signaling, then the biological activity can be inhibited, but non-blocking attenuation strategies are needed for certain therapeutic contexts

Engineering Contradiction:

Improvetarget molecule activityVSAvoidtherapeutic mechanism flexibility

Core Design Contradiction:

Quantity of substanceVSAdaptability or versatility

Solution Approach 1:

Instead of blocking the interaction between the target molecule and its binding partners (the conventional approach), the patent inverts the strategy by facilitating the internalization of the target molecule through binding to an internalizing effector protein. This causes the target to be actively taken into the cell and degraded, achieving attenuation through the opposite mechanism of direct blocking

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The internalizing effector protein serves multiple functions: it binds to the target molecule, facilitates its internalization into the cell, and directs it to degradative machinery. This multi-functional approach provides versatile therapeutic mechanisms that can be applied to different target molecules and disease contexts beyond simple blocking interactions

Inventive Principle:

Principle #6Universality (Multi-functionality)

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

This approach effectively attenuates the activity of target molecules without blocking their interaction with binding partners, offering a novel and efficient strategy for therapeutic applications.

Implementation Method 1

facilitating or bringing about a physical linkage between the target molecule and an internalizing effector protein

Methodology Applied

Scientific EffectPhysical linkage:

Data Source

PatentUS12297257B2Multispecific antigen-binding molecules and uses thereof

Publication Date: 2025.05.13 REGENERON PHARMACEUTICALS INC

AI summary

The present invention provides multispecific antigen-binding molecules and uses thereof. The multispecific antigen-binding molecules comprise a first antigen-binding domain that specifically binds a target molecule, and a second antigen-binding domain that specifically binds an internalizing effector protein. The multispecific antigen-binding molecules of the present invention can, in some embodiments, be bispecific antibodies that are capable of binding both a target molecule and an internalizing effector protein. In certain embodiments of the invention, the simultaneous binding of the target molecule and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention results in the attenuation of the activity of the target molecule to a greater extent than the binding of the target molecule alone. In other embodiments of the invention, the target molecule is a tumor associated antigen, and the simultaneous binding of the tumor associated antigen and the internalizing effector protein by the multispecific antigen-binding molecule of the present invention causes or facilitates the targeted killing of tumor cells.