Anti-TIGIT Antibody Formulation for Room-Temperature Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current formulations of anti-TIGIT antibodies are unstable and lack efficacy in treating various cancers due to their sensitivity to environmental conditions, necessitating improved stability and effectiveness for therapeutic applications.
Innovation Solution
A stable liquid pharmaceutical formulation of anti-TIGIT antibodies comprising specific CDRs, histidine, L-arginine, L-methionine, sucrose, and polysorbate 80, with a pH of 5.4+/−0.2, which maintains antibody stability and functionality for extended periods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional formulations are used, then the anti-TIGIT antibodies can be administered, but they lack stability and efficacy in treating cancers
Solution Approach 1:
The patent applies parameter changes by optimizing the pH of the formulation to 5.4 (within range 5.2-5.6), which is lower than conventional neutral pH formulations. This specific pH parameter change, combined with controlled antibody concentration (15-25 mg/mL), resolves the contradiction by achieving enhanced stability through precise parameter control while maintaining manufacturability
Solution Approach 2:
The patent employs composite materials by creating a multi-component formulation system that includes anti-TIGIT antibodies combined with specific excipients (histidine buffer, L-arginine, L-methionine, sucrose, and polysorbate 80). This composite formulation approach achieves synergistic stability enhancement while establishing a standardized manufacturing process that resolves the ease of manufacture concern
2Ease of operation
If the antibodies are stored at room temperature, then accessibility is improved, but stability decreases without proper formulation
Solution Approach 1:
The patent applies beforehand cushioning by incorporating multiple protective excipients in advance: sucrose (7-9% w/v) provides structural cushioning against thermal stress, polysorbate 80 (70-80 ppm) prevents aggregation, and amino acids (L-arginine 25-35 mM, L-methionine 8-12 mM) provide chemical cushioning against degradation. This pre-established protective system enables room temperature storage while maintaining antibody stability
Solution Approach 2:
The patent changes the pH parameter to 5.4 (within 5.2-5.6 range), which is optimally suited for room temperature stability. This parameter change, combined with the buffered histidine system (8-12 mM), creates a formulation environment that resist degradation at elevated temperatures, resolving the contradiction between accessibility and stability
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 formulation ensures the anti-TIGIT antibodies remain stable at temperatures between 5°C to 25°C for several months, enhancing their therapeutic potential in treating a wide range of cancers, including prostate, liver, colorectal, ovarian, breast, pancreatic, and lung cancers, among others.
Implementation Method 1
from 8 mM to 12 mM histidine
Implementation Method 2
from 25 mM to 35 mM L-Arginine; and from 8 mM to 12 mM L-methionine
Implementation Method 3
from 7% (w/v) to 9% (w/v) sucrose
Implementation Method 4
from 70 ppm to 80 ppm polysorbate 80
Data Source
AI summary
The present invention provides formulations comprising anti-TIGIT antibodies with CDRs identical to those shown in FIG. 3 (i.e., CDRs identical to those for CPA.9.086.H4(S241P), as described herein.