ActRII-Binding Proteins for Targeted Receptor Signaling Blockade

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Solution Overview

Problem

Existing treatments and diagnostics for conditions associated with ActRII and ActRII ligands, such as muscle disorders, fibrotic conditions, metabolic disorders, and cancer, are inadequate in effectively inhibiting or blocking ActRII signaling pathways.

Innovation Solution

Development of ActRII-binding proteins that specifically bind to ActRII receptors (ActRIIB and/or ActRIIA) to inhibit ligand binding, decrease phosphorylation of ALK4, ALK7, and Smads, and reduce ActRII-mediated signaling.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing treatments are used to address ActRII-mediated conditions, then some therapeutic intervention is provided, but the effectiveness in inhibiting ActRII signaling is insufficient

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidability to inhibit ActRII signaling

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces ActRII-binding proteins as intermediary molecules that specifically bind to ActRII receptors, blocking ligand binding and downstream signaling. These binding proteins act as mediators between the therapeutic need and the molecular target, providing reliable inhibition of ActRII-mediated pathways while maintaining specificity and reducing off-target effects.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If ActRII signaling is blocked to treat muscle disorders and fibrotic conditions, then therapeutic benefits are achieved, but the complexity of the treatment increases

Engineering Contradiction:

Improvepathological signalingVSAvoidtreatment complexity

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent extracts and isolates the specific binding function from complex antibody molecules, creating simplified ActRII-binding proteins that retain therapeutic efficacy. By focusing on the essential binding domain and removing unnecessary complexity, the treatment achieves effective ActRII blockade while reducing manufacturing and administration complexity.

Inventive Principle:

Principle #2Taking out (Extraction)

3Reliability

If specific binding to ActRII is achieved to reduce ligand binding, then signaling inhibition is improved, but the manufacturing precision requirements increase

Engineering Contradiction:

Improvespecificity of bindingVSAvoidbinding affinity control

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent employs parameter changes in the binding proteins' structural and chemical properties to optimize both specificity and manufacturability. By adjusting parameters such as binding affinity, stoichiometry, and structural stability, the invention achieves reliable ActRII-specific binding while maintaining feasibility for standard manufacturing processes.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12545736B2ActRII-binding proteins and uses thereof

Publication Date: 2026.02.10 ACCELERON PHARMA INC

AI summary

This disclosure provides ActRII-binding proteins such as anti-ActRIIA and anti-ActRIIB antibodies, and compositions and methods for making the ActRII-binding proteins. In certain embodiments, the ActRII-binding proteins inhibit, or antagonize ActRII activity. In addition, the disclosure provides compositions and methods for diagnosing and treating diseases and conditions associated with muscle wasting; a fibrotic condition; an inflammatory, cardiovascular, pulmonary, musculoskeletal, neurologic, ocular, skeletal, autoimmune, or metabolic disease or condition; wound healing; and cancer, and other ActRII-mediated diseases and conditions.