ILT7-Binding Protein Formulation for Light Oxidation Stability
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Solution Overview
Problem
Existing methods for manufacturing immunoglobulin-like transcript 7 (ILT7) binding proteins are limited by light-induced tryptophan oxidation in complementarity-determining regions (CDRs), which negatively impact potency and shelf life, and require engineering controls like specific lighting conditions and nitrogen overlays, increasing costs.
Innovation Solution
Formulations comprising 100 mg/mL to 350 mg/mL of ILT7 binding protein, 50 to 350 mM sucrose, 0.001% to 1% polysorbate-80, and L-methionine, with a buffer like histidine, citrate, or phosphate, reduce oxidation and aggregation, eliminating the need for nitrogen overlays and specific lighting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional formulations are used, then manufacturing costs are reduced, but light-induced tryptophan oxidation occurs in CDRs negatively impacting potency and shelf life
Solution Approach 1:
The patent converts the harmful effect of light exposure into a beneficial selection criterion by identifying specific tryptophan residues in CDRs that are susceptible to oxidation. This allows formulation scientists to针对性地 protect these specific residues through antioxidant selection and concentration optimization, rather than implementing costly engineering controls for all proteins.
Solution Approach 2:
The patent changes formulation parameters by optimizing antioxidant types and concentrations, buffer compositions, and pH levels to specifically prevent tryptophan oxidation in CDRs. This allows achieving protection without requiring nitrogen overlays or controlled lighting conditions during manufacturing.
2Ease of operation
If higher antibody concentrations are formulated, then administration convenience is improved, but aggregation rate and formulation viscosity increase
Solution Approach 1:
The patent changes formulation parameters including adding specific excipients, optimizing buffer compositions, and adjusting pH levels to stabilize high-concentration antibody formulations. These parameter changes prevent aggregation even at concentrations suitable for convenient administration.
3Reliability
If nitrogen overlay and controlled lighting are implemented, then oxidation is prevented, but manufacturing overhead and costs increase
Solution Approach 1:
The patent converts the need for complex engineering controls into a formulation science solution by selecting antioxidants that chemically prevent oxidation. This eliminates the need for nitrogen overlays and controlled lighting infrastructure during manufacturing.
Solution Approach 2:
The patent introduces antioxidant molecules as intermediaries between the antibody and oxygen/light. These antioxidants act as sacrificial agents that preferentially react with oxidizing species, protecting the antibody without requiring physical barriers or controlled environments.
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 formulations provide higher antibody concentrations, improved stability, and extended shelf-life, reducing manufacturing costs and overhead while maintaining biological activity.
Implementation Method 1
Light-induced tryptophan oxidation in complementarity-determining regions (CDRs) negatively impacts potency and shelf life of immunoglobulin-like transcript 7 (ILT7) binding proteins
Implementation Method 2
light-induced tryptophan oxidation
Implementation Method 3
delivery of higher antibody concentrations which were previously limited due to increased aggregation rate and formulation viscosity
Data Source
AI summary
Provided are immunoglobulin-like transcript 7 (ILT7)-binding proteins and methods of making, utilizing, and storing the same. Also provided are improved formulations comprising anti-ILT7 binding proteins and devices comprising the disclosed formulations.