Bottle Opener Antibody Format for Monovalent SSTR2 and CD3 Engagement
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Solution Overview
Problem
Current bispecific antibodies, such as those targeting somatostatin receptor 2 (SSTR2) and CD3, face challenges with bivalent engagement of co-target antigens, leading to nonspecific activation and potential toxicity, while fragment-based formats have stability and production issues due to lack of the constant region and associated functional properties.
Innovation Solution
Development of 'bottle opener' format antibodies with specific heavy and light chain configurations, including variant Fc domains and charged linkers, to achieve monovalent binding and enhanced stability, allowing for targeted engagement of SSTR2 and CD3 antigens without bivalent cross-linking.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If bispecific antibodies are designed to engage two different antigens, then therapeutic targeting capability is improved, but bivalent engagement leads to nonspecific activation and potential toxicity
Solution Approach 1:
The antibody is divided into separate heavy and light chain components with distinct functions. The heavy chain contains the Fc region for one antigen binding while the light chain contains the variable region for the second antigen binding. This segmentation allows monovalent engagement of each antigen independently, preventing bivalent cross-linking and nonspecific activation while maintaining dual targeting capability.
2Ease of manufacture
If antibody fragments are used to create bispecific formats, then manufacturing and penetration benefits are improved, but stability and production are worsened due to lack of constant region
Solution Approach 1:
The invention merges the advantages of antibody fragments (ease of manufacture, small size) with the stability of full-length antibodies by incorporating the Fc constant region into the heavy chain structure. The heavy chain contains both the Fc region for structural stability and the variable region for antigen binding, while the light chain provides the second antigen binding site. This hybrid structure maintains manufacturing benefits while achieving enhanced stability through the presence of the constant region.
Data Source
AI summary
The present invention is directed to antibodies, including novel antigen binding domains and heterodimeric antibodies, that bind somatostatin receptor 2 (SSTR2).