IL2Rγ-Binding Antibodies for Blocking STAT Phosphorylation
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Solution Overview
Problem
Current treatments for diseases associated with IL-2 receptor gamma (IL2Rγ) signaling, such as X-linked severe combined immunodeficiency, psoriasis, rheumatoid arthritis, asthma, Crohn's disease, and graft-versus-host disease, are inadequate in effectively blocking cytokine-induced STAT phosphorylation and graft vs host disease.
Innovation Solution
Development of antibodies and antigen-binding fragments that specifically target IL2Rγ, inhibiting cytokine-induced STAT phosphorylation and blocking graft vs host disease by using recombinant DNA techniques to produce antibodies in host cells like Chinese hamster ovary cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for IL2Rγ-related diseases are used, then disease management is attempted, but they fail to effectively block cytokine-induced STAT phosphorylation and graft vs host disease
Solution Approach 1:
The patent introduces a monoclonal antibody (e.g., H4H12922P2) as an intermediary substance that specifically binds to the IL-2 receptor gamma chain, thereby mediating the blockade of cytokine signaling. This antibody acts as a mediator between the therapeutic need and the molecular target, preventing cytokine-induced STAT phosphorylation without causing graft vs host disease.
Solution Approach 2:
The patent employs parameter changes by modifying the antibody structure (specific CDR sequences in heavy and light chains) to optimize binding affinity and specificity for the IL-2Rγ chain. By adjusting the amino acid sequences in the complementarity-determining regions, the antibody achieves enhanced effectiveness in blocking STAT phosphorylation while maintaining safety.
2Productivity
If antibodies are produced using recombinant DNA techniques in host cells, then production capability is achieved, but manufacturing complexity increases
Solution Approach 1:
The patent utilizes host cells (such as Chinese hamster ovary cells) that are engineered to autonomously produce the therapeutic antibody through recombinant DNA techniques. The host cell system serves itself by incorporating the antibody gene and performing the entire production process internally, including folding, post-translational modifications, and secretion, thereby achieving scalable production without requiring complex external manufacturing intervention.
Data Source
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AI summary
The present invention provides antibodies and antigen-binding fragments (e.g., human antibodies) that bind specifically to human IL2 receptor gamma (IL2Rγ). Methods for treating or preventing diseases mediated by IL2Rγ (e.g., graft vs host disease) using the antibodies and fragments are also provided along with methods of making the antibodies and fragments.