Anti-IFN-γ Antibody Epitope Binding for Immune Modulation
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Solution Overview
Problem
There is a need for effective anti-interferon gamma (IFN-γ) antibodies to neutralize IFN-γ-mediated activities and treat associated diseases, as existing therapies do not adequately address the dual role of IFN-γ in both inflammation and immune suppression.
Innovation Solution
Development of recombinant antibodies with specific CDR sequences (SEQ ID NOs: 120-155) that bind to defined epitopes on IFN-γ, inhibiting its activity and modulating immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If existing anti-IFN-γ therapies are used, then IFN-γ-mediated inflammation is suppressed, but T-cell immunity is not sufficiently enhanced
Solution Approach 1:
The patent applies parameter changes by developing antibodies with optimized binding affinity parameters (KD values) to IFN-γ. The anti-IFN-γ antibodies are engineered to bind with specific affinity ranges that simultaneously suppress inflammation and enhance T-cell immunity, resolving the contradiction through precise parameter optimization rather than qualitative changes.
Solution Approach 2:
The invention achieves multi-functionality by designing anti-IFN-γ antibodies that perform dual functions: suppressing IFN-γ-mediated inflammatory responses and enhancing T-cell immunity. This single agent addresses both contradictory requirements, making the therapy universally effective for conditions requiring both anti-inflammatory and immunomodulatory effects.
2Object-affected harmful factors
If IFN-γ signaling is blocked to reduce inflammation, then autoimmune disease symptoms improve, but immune surveillance capability may be compromised
Solution Approach 1:
The patent applies partial action by using anti-IFN-γ antibodies at optimized concentrations and dosing regimens that partially block IFN-γ signaling rather than complete inhibition. This partial blockade is sufficient to reduce autoimmune inflammation while preserving enough IFN-γ activity to maintain immune surveillance, resolving the contradiction between therapeutic efficacy and immune function preservation.
3Object-affected harmful factors
If high affinity anti-IFN-γ antibodies are used to neutralize IFN-γ activity, then inflammatory responses are suppressed, but off-target effects increase
Solution Approach 1:
The invention applies local quality by engineering antibodies with epitope-specific binding characteristics. The anti-IFN-γ antibodies are designed to bind to specific local regions (epitopes) on the IFN-γ molecule, ensuring that neutralization occurs through precise local interaction rather than global binding. This epitope-specific approach suppresses inflammatory responses while minimizing off-target effects by restricting the antibody's binding scope to the intended target region.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The antibodies effectively neutralize IFN-γ activity, inhibiting HLA-DR and PD-L1 expression, reducing cytokine production, and enhancing T-cell immunity, providing a therapeutic approach for IFN-γ-mediated syndromes.
Implementation Method 1
anti-interferon gamma antibodies and uses thereof... isolated antibody comprising: VH CDR1 comprising an amino acid sequence selected from SEQ ID NO: 120, 123, 126, 129, 144, 147, 150, or 153; VH CDR2 comprising an amino acid sequence selected from SEQ ID NO: 121, 124, 127, 130, 145, 148, 151, or 154; VH CDR3 comprising an amino acid sequence selected from SEQ ID NO: 122, 125, 128, 131, 146, 149, 152, or 155; VL CDR1 comprising an amino acid sequence selected from SEQ ID NO: 132, 135, 138, 141, 156, 158, 160, or 162; VL CDR2 comprising an amino acid sequence selected from SEQ ID NO: 133, 136, 139, 142, 157, 159, 161, or 163; and VL CDR3 comprising an amino acid sequence selected from SEQ ID NO: 134, 137, 140, or 143
Data Source
AI summary
Provided is an anti-INF-γ antibody. Also provided are a composition comprising the antibody and a pharmaceutical application of the antibody in treating IFN-γ mediated syndrome.