Engineered Antibody Constant Domains for Companion Animal Therapeutics
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Solution Overview
Problem
Current therapeutic monoclonal antibodies for companion animals, such as dogs, cats, and horses, lack optimized constant domain regions that effectively recruit immune cells and modulate effector functions, leading to suboptimal therapeutic efficacy and immunogenicity.
Innovation Solution
Development of recombinant polypeptides with engineered constant domain regions derived from companion mammals, capable of altered interactions with Fc receptors, enhancing effector functions like ADCC, CDC, and ADCP, and improving interaction with immune cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional constant domain regions are used in therapeutic monoclonal antibodies for companion animals, then the antibodies can be produced with standard immunoglobulin structures, but the therapeutic efficacy and immunogenicity are suboptimal
Solution Approach 1:
The patent applies parameter changes by introducing engineered substitutions at specific positions within the constant domain region of the immunoglobulin. These substitutions modify the amino acid sequence at defined locations to alter the interaction properties with Fc receptors and other immune components, thereby enhancing effector functions and therapeutic efficacy while maintaining manufacturability through a systematic approach to modification.
Solution Approach 2:
The patent implements local quality by making targeted modifications to specific regions within the constant domain rather than altering the entire immunoglobulin structure. The engineered substitutions are localized to specific positions that are critical for effector function, allowing optimization of therapeutic efficacy in specific areas while preserving the overall standard immunoglobulin structure and manufacturing simplicity.
2Reliability
If the constant domain region is engineered to enhance effector functions, then interaction with Fc receptors is improved, but the structural simplicity of the immunoglobulin is reduced
Solution Approach 1:
The patent uses parameter changes to modify the constant domain region by introducing engineered substitutions at specific positions. These changes alter the interaction parameters with Fc receptors and other immune components, enhancing effector functions. The systematic approach to modification allows for improved interaction while maintaining reasonable structural complexity through defined substitution patterns.
Solution Approach 2:
The patent applies segmentation by dividing the constant domain into specific regions with defined substitution positions. This allows targeted modification of specific segments that are critical for effector function while leaving other regions intact. The segmented approach enables enhancement of Fc receptor interaction without requiring complete redesign of the entire constant domain structure.
3Reliability
If engineered substitutions are introduced in the constant domain, then effector functions are enhanced, but the manufacturing process becomes more complex
Solution Approach 1:
The patent implements parameter changes by introducing engineered substitutions at specific positions in the constant domain region. These substitutions are designed to enhance effector functions while maintaining compatibility with standard recombinant protein production systems. The defined substitution patterns allow for modified polypeptide synthesis through conventional recombinant DNA techniques, balancing enhanced functionality with manufacturing feasibility.
Data Source
AI summary
The invention provides recombinant protein (e.g., a recombinant antibody or soluble receptor) having (i) a binding domain capable of specific binding to an epitope (for example an antibody variable domains, a receptor, a growth factor, a cytokine, or a fragment of any of the foregoing which is capable of specifically binding the desired epitope) and (ii) an effector domain comprising a constant domain region which is derived from immunoglobulin of a first species which is a companion mammal, e.g. dog, cat, or horse, having engineered substitutions at one or more positions and having an altered interaction with one or more FcRs or other ligands, and optionally enhanced effector function, relative to the parent constant domain region.