Anti-VLA1 (CD49A) antibody pharmaceutical compositions
Inventors
Fowler, Adam Jeremy • Bowe, Craig Michael • Yount, Wayne Curtis • Cobb, Nathan Jeremy • Kelly, Timothy Martin
Assignees
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Publication Number
US-10160808-B2
Publication Date
2018-12-25
Expiration Date
Abstract
Formulations of anti-VLA-1 antibodies are described.
Core Innovation
The invention relates to an aqueous antibody pharmaceutical composition comprising an anti-VLA-1 antibody. The anti-VLA-1 antibody is defined as having one or both of a light chain variable region with the amino acid sequence of SEQ ID NO:4 and a heavy chain variable region with the amino acid sequence of SEQ ID NO:5. The composition is formulated at a pH of 6.0 with 30 mM histidine, 250 mM sorbitol, 0.01% polysorbate 20, and 180 mg/mL of the anti-VLA-1 antibody.
The composition includes defined excipients and product-property constraints, including being substantially free of citrate and having specified osmolality and viscosity limits. Stability is indicated by analytical criteria, including impurities measured by reducing capillary electrophoresis sodium dodecyl sulfate (CE-SDS) and total aggregation measured by size exclusion chromatography. The document describes stability after storage at 2 to 8°C for at least 3 years, with a duration variant of at least 48 months.
The description further identifies SAN-300 formulations prepared with histidine versus acetate buffers, including sorbitol and polysorbate excipient at the respective formulation pH values. The histidine-buffered aqueous antibody pharmaceutical composition demonstrates improved stability compared with acetate-buffered formulations, with reduced aggregation and reduced changes in charge heterogeneity under elevated temperature conditions.
Claims Coverage
The independent claim defines a histidine-based aqueous anti-VLA-1 antibody composition at pH 6.0 with quantitative formulation components and a long-term stability requirement at 2 to 8°C, indicated by aggregation by size exclusion chromatography. The dependent claims further refine excipient compatibility and add quantitative product-property and stability criteria using osmolality, viscosity, reducing CE-SDS impurity assessment, and extended storage duration. Two core inventive features are presented in the independent claims.
A histidine-based aqueous anti-VLA-1 antibody composition at pH 6.0
An aqueous antibody pharmaceutical composition comprising 180 mg/mL of the anti-VLA-1 antibody having one or both of a light chain variable region with the amino acid sequence of SEQ ID NO:4 and a heavy chain variable region with the amino acid sequence of SEQ ID NO:5, 30 mM histidine, 250 mM sorbitol, and 0.01% polysorbate 20, wherein the aqueous antibody pharmaceutical composition has a pH of 6.0.
Long-term cold storage stability with limited total aggregation by SEC
The aqueous antibody pharmaceutical composition is stable after storage at 2 to 8°C for at least 3 years, as indicated by the presence of less than 10% total aggregation as assessed by size exclusion chromatography.
Across the independent claim and its dependents, the claim coverage centers on an aqueous anti-VLA-1 antibody composition using histidine, sorbitol, and polysorbate 20 at pH 6.0, together with demonstrated long-term stability at 2 to 8°C. The dependents add constraints on excipient compatibility, physical properties, and stability indication by reducing CE-SDS impurities, including extended duration variants.
Stated Advantages
Improved stability of histidine-buffered SAN-300 formulations compared with acetate-buffered formulations, with reduced aggregation and reduced changes in charge heterogeneity under elevated temperature conditions.
Provides long-term stability after storage at 2 to 8°C for at least 3 years, indicated by less than 10% total aggregation as assessed by size exclusion chromatography.
Provides stability after storage at 2 to 8°C for at least 3 years indicated by less than 15% impurities measured by reducing CE-SDS.
Provides stability after storage at 2 to 8°C for at least 48 months.
Maintains formulation compatibility constraints such as being substantially free of citrate.
Documented Applications
Formulations are described for SAN-300 aqueous antibody pharmaceutical composition, with stability evaluation under intended storage conditions including 2 to 8°C, inverted storage, and elevated humidity/temperature conditions as part of the documented stability study.
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