Multispecific Binding Molecules for BBB Crossing and CNS Targeting

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Existing treatments for CNS diseases face challenges in delivering therapeutics across the blood brain barrier and targeting specific CNS targets within the CNS, with existing shuttle technologies being inefficient, invasive, and associated with immunogenicity and off-target issues.

Innovation Solution

Development of multispecific binding molecules with a first domain targeting the blood brain barrier and a second domain targeting neuron, astrocyte, or glial cell targets, enhancing the delivery of therapeutics across the blood brain barrier and to specific CNS targets, while minimizing invasiveness and immunogenicity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing shuttle technologies (anti-TFR antibodies) are used to enhance passage across the blood brain barrier, then delivery of therapeutics to CNS is improved, but immunogenicity and off-target issues worsen

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidimmunogenicity and off-target issues

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses a multispecific binding molecule as an intermediary that binds to both the blood brain barrier (via anti-TFR antibody component) and the CNS target (via second binding domain). This intermediary approach allows the therapeutic to be shuttled across the BBB without the anti-TFR antibody directly contacting and triggering immune responses in the CNS, thereby reducing immunogenicity while maintaining delivery efficiency.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of manufacture

If non-specific therapeutics are used, then ease of manufacture is improved, but targeting precision to specific CNS targets worsens

Engineering Contradiction:

Improvetherapeutic productionVSAvoidtargeting precision

Core Design Contradiction:

Ease of manufactureVSManufacturing precision

Solution Approach 1:

The patent merges a readily manufacturable therapeutic with a multispecific binding molecule that provides precise targeting. The binding molecule combines anti-TFR antibody (for BBB crossing) and a second binding domain (for CNS target specificity), thereby enabling precise targeting without complicating the manufacturing of the core therapeutic agent.

Inventive Principle:

Principle #5Merging (Combining)

3Reliability

If invasive delivery methods are used to overcome the blood brain barrier, then delivery efficiency is improved, but patient safety and comfort worsen

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidinvasiveness

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The multisspecific binding molecule serves as a non-invasive intermediary that mediates transport across the blood brain barrier by binding to endogenous receptors (TFR) on BBB endothelial cells. This approach leverages the body's own transport mechanisms rather than requiring invasive procedures, thereby maintaining delivery efficiency while eliminating surgical or procedural invasiveness.

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20250304709A1Multispecific binding molecules and methods of use thereof

Publication Date: 2025.10.02 ELI LILLY & CO

AI summary

Multispecific binding molecules having a first binding domain targeting a blood brain barrier target and a second binding domain targeting a neuron target, astrocyte target and/or glial cell target, and uses thereof in aiding the treatment of central nervous system diseases including neurodegenerative diseases such as Alzheimer's disease, Huntington's disease, Parkinson's diseases, Progressive Supranuclear Palsy (PSP), Amyotrophic Lateral Sclerosis (ALS), Frontal Temporal Dementia (FTD), autism, catalepsy, encephalitis, migraine, and Tourette's.