Antibody formulations
Inventors
Fowler, Adam Jeremy • Bowe, Craig Michael • Yount, Wayne Curtis • Cobb, Nathan Jeremy • Kelly, Timothy Martin
Assignees
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Publication Number
US-10316095-B2
Publication Date
2019-06-11
Expiration Date
Abstract
Formulations of anti-VLA-1 antibodies are described.
Core Innovation
An aqueous pharmaceutical composition comprises an anti-Very Late Antigen-1 (VLA-1) antibody at a concentration of about 100 mg/ml to about 225 mg/ml. The anti-VLA-1 antibody comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 5. The composition includes at least one buffer selected from histidine buffer, acetate buffer, succinate buffer, citrate buffer, glutamate buffer, and phosphate buffer.
The aqueous pharmaceutical composition further comprises at least one additional excipient selected from sorbitol, sodium chloride, sucrose, trehalose, and mannitol at a concentration of about 100 mM to about 300 mM. The formulation optionally includes a surfactant such as polysorbate 20 or polysorbate 80, and has a pH in a range of about 4.5 to about 7. The disclosed formulations are characterized by physicochemical and quality measurements including protein, viscosity, osmolality, appearance, particulate control, purity/aggregation trends by reduced SDS-PAGE and SEC, and charge heterogeneity by cation exchange chromatography under storage and stress conditions.
The aqueous pharmaceutical composition is stable after storage at 2°C to 8°C for at least 3 years, as indicated by less than 10% total aggregation as assessed by size exclusion chromatography. The formulation is described as maintaining stability under stress-related conditions, including controlled aggregation and protein loss assessed by DLS and spectroscopy.
Claims Coverage
The independent claim coverage centers on a defined anti-VLA-1 antibody composition with selected buffers and additional excipients, and long-term stability at 2°C to 8°C defined by a less than 10% total aggregation threshold by size exclusion chromatography. Three inventive features are merged across the provided content.
Anti-VLA-1 antibody with defined variable-region sequences
An aqueous pharmaceutical composition comprising an anti-Very Late Antigen-1 (VLA-1) antibody wherein the antibody comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 4 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 5, at about 100 mg/ml to about 225 mg/ml.
Selected buffer system and additional excipient system
An aqueous pharmaceutical composition wherein at least one buffer is selected from histidine buffer, acetate buffer, succinate buffer, citrate buffer, glutamate buffer, and phosphate buffer, and at least one additional excipient is selected from sorbitol, sodium chloride, sucrose, trehalose, and mannitol at a concentration of about 100 mM to about 300 mM.
Long-term stability with aggregation limit by size exclusion chromatography
An aqueous pharmaceutical composition stable after storage at 2°C 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.
The claim scope is directed to a defined anti-VLA-1 antibody composition, its selected buffer and excipient formulation, and a long-term storage stability requirement expressed by a size exclusion chromatography aggregation limit.
Stated Advantages
Provides stability after storage at 2°C to 8°C for at least 3 years with less than 10% total aggregation as assessed by size exclusion chromatography.
Improved stability versus acetate, including better retention of monomer/charge and reduced changes under elevated temperatures.
Documented Applications
Subcutaneous administration context for anti-VLA-1 inflammatory/autoimmune diseases is described in the provided content, including rheumatoid arthritis.
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