Retifanlimab Formulation Buffering for Long-Term Antibody Stability
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is an unmet need for antibody compositions that effectively target PD-L1-expressing tumors, including those with low PD-L1 expression or that have failed other PD-1 therapies, to enhance the immune response against cancer.
Innovation Solution
Pharmaceutical compositions comprising an anti-human PD-1 antibody (retifanlimab) with buffering agents like acetate, sucrose, and polysorbate 80, formulated to maintain stability and efficacy for extended shelf-life and administration, including containers and kits for cancer treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Device complexity
If retifanlimab is stored without buffering agents and stabilizers, then the formulation is simpler, but the monomeric purity and stability deteriorate over time
Solution Approach 1:
The patent applies preliminary action by pre-formulating the retifanlimab antibody with buffering agents (acetate, succinate, or citrate) and stabilizers (polysorbate 80, sucrose, or trehalose) before storage and administration. This pre-prepared formulation maintains monomeric purity and structural stability over extended periods (up to 60 months) without requiring complex real-time stabilization during storage or transport.
2Duration of action of stationary object
If retifanlimab is formulated with buffering agents and stabilizers for extended shelf-life, then the stability and shelf-life are improved, but the formulation complexity and manufacturing difficulty increase
Solution Approach 1:
The patent applies parameter changes by systematically varying the concentration ranges of buffering agents (5-30 mM acetate, 5-20 mM succinate, or 5-15 mM citrate) and stabilizers (50-130 mg/mL polysorbate 80, 50-130 mg/mL sucrose, or 50-130 mg/mL trehalose) to optimize both stability and manufacturability. These defined parameter ranges enable extended shelf-life (up to 60 months) while maintaining practical manufacturing feasibility through standardized formulation processes.
3Reliability
If retifanlimab is formulated with specific buffering agents and stabilizers, then the pH and osmolality are optimized for stability, but the formulation complexity increases
Solution Approach 1:
The patent applies universality by designing a multi-functional formulation system where buffering agents serve dual purposes: pH control (maintaining 4.0-6.5) and osmolality adjustment. The stabilizers (polysorbate 80, sucrose, trehalose) simultaneously protect the antibody structure, prevent aggregation, and contribute to osmolality management. This integrated approach optimizes biological activity and reliability while managing formulation complexity through coordinated selection of components.
Data Source
AI summary
The present disclosure is provides pharmaceutical compositions, for storage and administration, comprising a human PD-1 (“hPD-1”) antibody (“retifanlimab”) and buffering agents. The disclosure further provides containers and kits comprising such pharmaceutical compositions. The disclosure further provides the use of such pharmaceutical compositions, containers, and kits containing retifanlimab in the treatment of a cancer, and in certain aspects treatment of a cancer expressing PD-L1.