mAbs | Notable Targeting BCMA Nanobody Patent Landscape Analysis

This study systematically analyzes the patent landscape of Nbs technology, focusing on sequence, structural characteristics, and epitope binding trends of BCMA-targeting Nbs, providing theoretical support for next-generation Nbs design and patent strategies.

 

Literature Overview
Published in mAbs, this paper 'Exploring the nanobody patent landscape: a focus on BCMA sequences and structural analysis' reviews current patent landscapes and trends in nanobody (Nbs) technology, analyzing epitope binding patterns, sequence features, and structural properties targeting B-cell maturation antigen (BCMA), offering theoretical and experimental foundations for Nbs drug development.

Background Knowledge
Nanobodies (Nbs), also known as single-domain antibodies (sdAbs), derive from the variable heavy chain domains (VHH) of camelid or cartilaginous fish heavy-chain antibodies. They offer advantages such as low molecular weight, high stability, and strong tissue penetration. BCMA is a critical therapeutic target in multiple myeloma (MM), with several Nbs candidates already in clinical trials, including CAR-T cell therapy cilta-cel (Carvykti®). Despite Nbs' clinical potential, systematic analyses of their patent landscape and structural features remain limited. This study addresses these gaps through patent analysis and structural modeling, revealing sequence conservation, epitope distribution, and structural diversity in BCMA-targeting Nbs to inform novel drug design and intellectual property protection.

 

 

Research Methods and Experiments
The research team retrieved 12,619 Nbs-related patent families from the Derwent Innovation database, filtered to 3,032 key families after excluding SARS-CoV-2-related patents. Sequence analysis of BCMA-targeting Nbs employed Clustal Omega and AlphaFold3 (AF3) for structural modeling. Physicochemical properties and post-translational modification sites were analyzed using Expasy ProtParam and abYsis. Network analysis (Gephi) and statistical tools (R language) assessed patent citation networks and modification site distribution significance.

Key Conclusions and Perspectives

• Global Nbs patent applications are growing rapidly, with China and the U.S. as primary jurisdictions, covering therapeutic, diagnostic, and production technologies.
• BCMA remains a critical target in Nbs development, with multiple candidates (e.g., CAR-T cilta-cel) in clinical phases.
• BCMA-targeting Nbs exhibit high sequence conservation, particularly in complementarity-determining regions (CDRs), but low structural similarity, indicating diverse structural adaptability.
• Structural similarity can exist despite sequence divergence, highlighting the importance of structural analysis in patent protection.
• Post-translational modification sites (e.g., methionine oxidation and asparagine isomerization) show uneven distribution in framework regions and CDRs, suggesting engineering opportunities for optimization.
• Epitope mapping of BCMA reveals high-frequency binding sites (e.g., E12, L18, H19), some overlapping with marketed drugs (teclistamab, elranatamab), necessitating attention to epitope competition in novel Nbs development.
• Structural modeling and sequence analysis provide theoretical frameworks for epitope distribution and binding modes, guiding patent strategy optimization.

Research Significance and Prospects
The study underscores Nbs' potential in cancer immunotherapy and emphasizes structural analysis in patent landscaping and drug design. Future work should integrate experimental validation with computational approaches to refine structure-guided Nbs engineering, advancing multispecific formats and cell therapy innovations.

 

 

Conclusion
Nanobodies (Nbs), with their unique properties, are becoming pivotal tools in biopharmaceuticals, particularly for multiple myeloma (MM) targeting via BCMA. This study provides a comprehensive analysis of sequence and structural features in BCMA-targeting Nbs through patent and structural modeling, offering theoretical foundations for next-generation Nbs design and intellectual property protection. It further highlights structural analysis as a critical factor in defining patent scope, opening new avenues for Nbs innovation and IP strategies.

 

Jiaqi Xu, Yan Wang, Ni Yuan, Guang Hu, and Yuanjia Hu. Exploring the nanobody patent landscape: a focus on BCMA sequences and structural analysis. mAbs.