Anti-CD96 Antibody Binding Regions for Immune Checkpoint Blocking
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Solution Overview
Problem
Existing methods for reducing CD96 activity in mammals, such as anti-CD96 antibodies, are limited in their effectiveness and specificity, failing to adequately inhibit immune regulatory functions mediated by CD96, CD155, CD226, and TIGIT, which can contribute to immune inhibition and tumor growth.
Innovation Solution
Development of antibodies with specific hypervariable regions that bind to human CD96 with high affinity, inhibiting or blocking immune regulatory effects mediated by CD96, CD155, CD226, and TIGIT, thereby providing compositions and methods for treating diseases responsive to these interactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-CD96 antibodies are used to reduce CD96 activity, then some immune regulatory function is inhibited, but the effectiveness and specificity are insufficient to adequately block immune inhibition and tumor growth
Solution Approach 1:
The patent applies local quality by designing antibodies with specifically engineered hypervariable regions (HVRs) that target particular epitopes on CD96. The antibodies contain precisely defined HVR sequences (HVR-L1, HVR-L2, HVR-L3, HVR-H1, HVR-H2, HVR-H3) that are optimized for high-affinity binding to CD96, while other regions of the antibody maintain standard structures. This localized optimization of binding regions achieves superior inhibitory effectiveness without requiring complete redesign of the entire antibody molecule.
Solution Approach 2:
The patent employs parameter changes by modifying the amino acid sequences of the hypervariable regions to achieve optimal binding affinity and specificity. The antibodies contain specific amino acid compositions in their HVRs that are tuned to match CD96 epitopes, with defined sequence variations that enhance binding strength. This parameter optimization allows the antibodies to effectively block CD96-CD155 interactions and inhibit immune regulatory functions with high reliability.
2Productivity
If antibodies with high affinity for CD96 are developed to enhance immune response, then tumor growth inhibition is improved, but the complexity of antibody design and production increases
Solution Approach 1:
The patent applies segmentation by dividing the antibody into distinct functional regions with specific roles. The hypervariable regions (HVR-L1, HVR-L2, HVR-L3, HVR-H1, HVR-H2, HVR-H3) are segmented as the antigen-binding domain responsible for high-affinity CD96 recognition, while the constant regions maintain standard immunoglobulin structures for effector functions. This segmentation allows independent optimization of binding affinity in the HVRs without complicating the overall antibody production process.
Solution Approach 2:
The patent achieves universality by designing antibodies that can bind to multiple epitopes or isoforms of CD96 through their hypervariable regions. The antibodies are engineered to recognize conserved regions of CD96 while maintaining high affinity, allowing them to effectively inhibit various CD96-mediated immune regulatory pathways. This multi-functional design enables a single antibody formulation to address diverse cancer types and immune inhibition mechanisms.
Data Source
AI summary
The present disclosure provides binding proteins, such as antibodies and antigen-binding fragments, which specifically bind to human CD96 receptor protein (hu-CD96) and are capable of decreasing, inhibiting, and/or fully-blocking immune regulatory effects mediated by hu-CD96. The present disclosure also provides methods of using the antibodies (and compositions thereof) to treat diseases and conditions responsive to decreasing, inhibiting and/or blocking immune regulatory function or activity mediated by CD96 binding to CD155, including effects arising from CD96 interactions with CD226 and/or TIGIT.