Retifanlimab Antibody Formulation with Buffering for 60-Month Stability
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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, are provided in containers and kits for the treatment of cancers expressing PD-L1.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If conventional antibody formulations are used, then short-term stability is achieved, but long-term stability (beyond 24 months) cannot be maintained
Solution Approach 1:
The patent applies parameter changes by optimizing the pH range to 4.0-6.5 and specifying precise concentrations of buffering agents (acetate 5-30 mM), sucrose (50-130 mg/mL), and polysorbate 80 (0.02-0.6 mg/mL). These parameter adjustments enable the formulation to maintain antibody stability for up to 60 months, resolving the contradiction between long-term stability and efficacy maintenance.
Solution Approach 2:
The patent employs a composite formulation system combining multiple stabilizing components: acetate buffer, sucrose as a cryoprotectant/stabilizer, and polysorbate 80 as a surfactant. This composite approach creates synergistic effects that preserve antibody structure and function over extended storage periods, achieving both long-term stability and sustained efficacy.
2Duration of action of stationary object
If storage time is extended to 60 months, then long-term availability is improved, but protein degradation and aggregation increase
Solution Approach 1:
The patent applies preliminary action by incorporating stabilizing agents (sucrose and polysorbate 80) into the formulation before storage begins. These agents proactively prevent protein degradation and aggregation mechanisms from occurring during the 60-month storage period, thereby maintaining monomeric purity throughout extended storage.
Solution Approach 2:
The formulation includes buffering agents and stabilizers that act as a protective cushion against environmental stresses (pH variations, oxidation, aggregation) that would otherwise degrade the antibody during long-term storage. This beforehand cushioning enables extended storage duration while preserving protein integrity.
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.