Single-Domain Anti-TIGIT Antibodies for Modular Multispecific Design

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Solution Overview

Problem

There is a need for therapeutic molecules and methods to modulate TIGIT-mediated immune cell regulation for immune therapy and cancer treatment, as TIGIT and PDL1 interactions downregulate T cell activation and cytokine secretion, allowing cancer cells to evade the host immune system.

Innovation Solution

Development of monoclonal antibodies, including multispecific antibodies that bind to TIGIT and PDL1 with high affinity, to increase immune response and provide improved anti-tumor efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If TIGIT/PVR interaction is inhibited to enhance immune cell activity, then antitumor activity is improved, but the complexity of therapeutic molecule development increases

Engineering Contradiction:

Improveimmune cell activationVSAvoidtherapeutic molecule structure

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the antibody structure into single-domain units (VHH) that can independently bind to TIGIT. This modular approach allows for simplified construction of multispecific antibodies while maintaining high affinity binding, thus improving immune cell activation without proportionally increasing complexity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates multispecific antibodies that can simultaneously bind to multiple targets (TIGIT and other antigens such as PD-L1, CD3, CD137). This multi-functionality allows a single therapeutic molecule to engage multiple immune checkpoint pathways, enhancing antitumor activity through coordinated immune cell activation across different mechanisms

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If multisspecific antibodies targeting multiple antigens are developed to enhance immune response, then anti-tumor efficacy is improved, but manufacturing complexity increases

Engineering Contradiction:

Improveanti-tumor efficacyVSAvoidantibody production

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses segmented single-domain antibody units that can be independently produced and then assembled into multispecific configurations. This modular manufacturing approach simplifies production compared to traditional full-length antibody engineering, as each domain can be expressed separately and combined through standardized linkers or fusion techniques

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs parameter changes in the antibody structure, specifically using single-domain formats instead of traditional IgG structures. This fundamental parameter change enables simpler expression systems and manufacturing processes while maintaining or enhancing binding affinity and functional efficacy against multiple tumor-associated antigens

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12415858B2Anti-tigit antibodies, multispecific antibodies comprising the same, and methods of using the same

Publication Date: 2025.09.16 SHANGHAI HENLIUS BIOTECH INC

AI summary

Provided are anti-TIGIT antibodies that bind to “T cell immunoreceptor with Ig and ITIM domains (TIGIT)”, including multispecific anti-TIGIT antibodies with binding specificity for TIGIT and one or more additional antigen, and methods of using the same. In certain embodiments, the anti-TIGIT antibodies comprises a single domain antibody that binds to TIGIT. In certain embodiments, the one or more additional antigen comprises Programmed cell death ligand 1 (PDL1).