Multispecific VHH Antibodies for Precise Multi-Antigen Binding

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Solution Overview

Problem

Existing antibodies lack specificity and versatility in targeting multiple antigens, particularly OX-40, CD40, 4-1BB, HSA, IL-22, and EGFR, limiting their effectiveness in immune response modulation and cancer treatment.

Innovation Solution

Development of monospecific and multivalent single-chain antibodies, including VHH domains and conventional antibody constant domains, that can target one or multiple antigens with high specificity and valency, such as OX-40, CD40, 4-1BB, HSA, and EGFR, through various configurations and linkers.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If conventional antibodies are used to target multiple antigens, then versatility in targeting is improved, but specificity and binding affinity deteriorate

Engineering Contradiction:

Improveability to target multiple antigensVSAvoidbinding specificity and affinity

Core Design Contradiction:

Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The patent divides the antibody structure into separate functional domains: VHH domains (each targeting a specific antigen) and Fc domains (providing effector functions). This segmentation allows each VHH domain to maintain high specificity for its target antigen while the overall antibody construct achieves multivalency and versatility through combination of multiple VHH domains.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates multivalent single-chain antibodies that can simultaneously target multiple antigens (OX-40, CD40, 4-1BB, HSA, IL-22, EGFR) by incorporating multiple different VHH domains in a single polypeptide chain. This universal design enables one antibody molecule to perform multiple targeting functions while maintaining high affinity for each specific antigen through its individual VHH domains.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If multivalent antibody constructs are created to enhance immune response, then therapeutic efficacy is improved, but molecular weight and complexity increase

Engineering Contradiction:

Improvetherapeutic efficacy and immune response modulationVSAvoidantibody structure complexity and molecular weight

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent merges multiple VHH domains and Fc domains into a single continuous polypeptide chain to form a multivalent single-chain antibody. This merging approach achieves multivalency (enhancing therapeutic efficacy through increased avidity and immune response modulation) while maintaining a relatively compact and manageable molecular structure compared to traditional multi-subunit antibody constructs.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent creates composite antibody structures by combining camelid VHH domains with mammalian Fc domains in a single polypeptide. This composite design integrates the small size and high stability of VHH domains with the effector function capabilities of Fc domains, achieving enhanced therapeutic efficacy while controlling overall molecular complexity.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS20250376535A1Monospecific and multi-specific antibodies

Publication Date: 2025.12.11 BEIJING STARMAB BIOMED TECH LTD

AI summary

Disclosed herein are monospecific and multi-specific antibodies with specificities for one or more of OX40, CD40, 4-1BB, HSA, IL-22, or EGFR. Specifically, the disclosure provides variable heavy (VHH) domains of the antibodies with specificities for one or more of OX40, CD40, 4-1BB, HSA, IL-22, or EGFR, and associated sequences. Further discloses are methods of using the monospecific or multi-specific antibodies for treating ah autoimmune disease.