Pharmaceutical compositions of a PD-1 antibody and use of the same
Inventors
Sampathkumar, Krishnan • Zhou, Yan • Burke, Stephen James
Assignees
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Publication Number
US-12364756-B2
Publication Date
2025-07-22
Expiration Date
Abstract
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.
Core Innovation
The invention relates to retifanlimab pharmaceutical compositions and drug products for storage, intravenous administration, and in-use compatibility. The composition comprises retifanlimab, acetate comprising acetic acid and an acetate salt, sucrose, polysorbate 80, and water, with an acidic pH of about 4.0 to about 6.5, including about 4.5 to about 5.7 and about 4.8 to about 5.4.
The formulation design uses an acetate buffer system together with sucrose and polysorbate 80 to provide a retifanlimab composition suitable for storage and intravenous administration. The document also includes container and kit concepts that hold the pharmaceutical composition in defined strengths and fill amounts, and a kit comprising a container holding a pharmaceutical composition with alternative retifanlimab, glacial acetic acid, sodium acetate trihydrate, sucrose, and polysorbate 80 compositions in water.
The disclosure evaluates in-use compatibility and stability under preparation and storage conditions associated with IV administration. It reports that filtration through 0.2 bcm low protein binding filters reduces visible and proteinaceous subvisible particulates without quality impact, that temperature cycling and shaking increase subvisible particles while pH, concentration, potency, and HPLC/cIEF profiles are largely unchanged, and that post-infusion filtration eliminates visible particles and reduces subvisible particle counts.
Claims Coverage
The provided independent claims cover 2 inventive features: a formulation-defined pharmaceutical composition and a kit holding defined retifanlimab compositions. Across the independent claims, the inventive features revolve around retifanlimab at defined concentration ranges, an acetate buffer comprising acetic acid and an acetate salt, sucrose, polysorbate 80, and an acidic pH window.
Acidic retifanlimab acetate-sucrose-polysorbate 80 formulation in water
A pharmaceutical composition comprising retifanlimab; acetate comprising acetic acid and an acetate salt; sucrose; polysorbate 80; and water, wherein the composition has a pH of about 4.0 to about 6.5.
Kit with container holding defined acidic retifanlimab excipient sets and optional administration instructions
A kit comprising a container holding a pharmaceutical composition comprising one of several defined retifanlimab, glacial acetic acid, sodium acetate trihydrate, sucrose, and polysorbate 80 compositions in water, with pH windows of about 4.5 to about 5.7 or about 4.8 to about 5.4, and optionally instructions for administration to a subject in need thereof.
The claim coverage is centered on retifanlimab formulated with an acetate buffer, sucrose, and polysorbate 80 in water under an acidic pH range, with the kit claim further specifying alternative formulation sets, narrower pH windows, and optional administration instructions.
Stated Advantages
Monomeric purity and heterogeneity profile are maintained over storage.
Filtration through 0.2 bcm in-line/add-on filters reduces visible and proteinaceous subvisible particulates without quality impact after simulated worst-case storage and infusion.
Temperature cycling/shaking is reported to largely maintain pH, concentration, potency, and HPLC/cIEF profiles while increasing subvisible particles.
Post-infusion filtration eliminates visible particles and reduces subvisible particle counts.
Microbial challenge shows no increase in microbial growth for diluted solutions across storage conditions.
Multi-method stability assessment supports shelf-life, including long-term and accelerated stability results.
Documented Applications
Treating cancers including PD-L1-expressing tumors using intravenous administration.
In-use compatibility evaluation for retifanlimab IV solutions and drug product, including storage up to about 6 h at room temperature and about 24 h at about 28C followed by infusion.
Use of dilution conditions described in the partial content for microbial challenge testing of retifanlimab solutions diluted in 0.9% saline and D5W across storage conditions.
Support for post-infusion filtration to eliminate visible particles and reduce subvisible particle counts.
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