Buffer formulations for enhanced antibody stability
Inventors
Cini, John • Nagi, Athena • Taddei, Maria
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-10376582-B2
Publication Date
2019-08-13
Expiration Date
Abstract
The invention provides buffered formulations of adalimumab. The formulations comprise a buffer comprising an acetate salt, mannitol, glacial acetic acid, sodium chloride, and polysorbate 80. The formulations have an acidic pH, and enhance the thermal, conformational and colloidal stability of antibodies, including the adalimumab antibody.
Core Innovation
The disclosed invention provides buffered antibody formulations comprising an antibody with a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2. The formulations include a buffer having an acetate salt, mannitol, glacial acetic acid, and sodium chloride, together with polysorbate 80, and are characterized by an acidic pH from about 5.1 to about 5.3.
The buffer composition is defined by specific concentration ranges for an acetate salt, mannitol, glacial acetic acid, and sodium chloride, with polysorbate 80 present at a defined level. In certain embodiments, the acetate salt is sodium acetate trihydrate, the pH is about 5.2, and the antibody amount is constrained to specified mass ranges.
The invention addresses the need for improved formulation stability of an anti-TNFα antibody (adalimumab/ONS-3010) in buffered aqueous formulations. The disclosed content states that comparative stressed, accelerated, and real-time stability results indicate improved thermal, conformational, and colloidal stability for formulations described as “acetate LS/HM” versus a reference formulation, including reduced aggregation/high molecular weight species, reduced degradation/fragmentation, reduced oxidation-related post-translational modifications, and maintained potency in a L929 cell-based bioassay.
Claims Coverage
The document provides four independent claim categories covering buffered antibody formulations and a buffer formulation for antibody storage. Across these independent claims, the core inventive elements are the defined heavy and light chain sequences, the acetate salt/mannitol/glacial acetic acid/sodium chloride buffer system, the specified polysorbate 80 range, and the acidic pH range of about 5.1 to about 5.3, including embodiments fixing pH to about 5.2 and specifying sodium acetate trihydrate.
Buffered antibody formulation with defined heavy and light chain sequences
A buffered antibody formulation comprising an antibody comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2.
Acetate/mannitol/glacial acetic acid/sodium chloride buffer system at acidic pH
A buffer comprising an acetate salt, mannitol, glacial acetic acid, and sodium chloride, wherein the antibody formulation has a pH of from about 5.1 to about 5.3.
Polysorbate 80 in a defined v/v range
About 0.07% (v/v) to about 0.15% (v/v) of polysorbate 80.
Specific pH and fixed buffer component targets
A buffered antibody formulation comprising an antibody comprising a heavy chain comprising the amino acid sequence of SEQ ID NO: 1 and a light chain comprising the amino acid sequence of SEQ ID NO: 2, a buffer comprising about 1 mM of sodium acetate trihydrate, about 203 mM of mannitol, about 19 mM of glacial acetic acid, and about 26.35 mM of sodium chloride, and about 0.1% (by volume) of polysorbate 80, wherein the antibody formulation has a pH of about 5.2.
Antibody storage buffer formulation
A buffer formulation for antibody storage, comprising a buffer comprising from about 0.7 mM to about 1.3 mM of an acetate salt, from about 200 mM to about 206 mM of mannitol, from about 16 mM to about 22 mM of glacial acetic acid, and from about 24 mM to about 28 mM of sodium chloride, and about 0.07% (v/v) to about 0.15% (v/v) of polysorbate 80, wherein the formulation has a pH of from about 5.1 to about 5.3.
Across the independent claims, the coverage centers on buffered aqueous formulations for an antibody with heavy chain SEQ ID NO: 1 and light chain SEQ ID NO: 2, formulated with a defined acetate salt/mannitol/glacial acetic acid/sodium chloride buffer system, polysorbate 80 at a defined level, and an acidic pH from about 5.1 to about 5.3, including embodiments specifying sodium acetate trihydrate and pH of about 5.2. A related independent claim covers a buffer-only formulation for antibody storage with the same defined buffer composition and acidic pH range.
Stated Advantages
Improved thermal, conformational, and colloidal stability compared with a reference formulation.
Reduced aggregation/high molecular weight species.
Reduced degradation/fragmentation.
Maintained potency in a L929 cell-based bioassay.
Reduced oxidation-related post-translational modifications.
Stability maintained over extended time, including up to 18 months at 2–8°C and ≤8°C.
Documented Applications
Therapeutic treatment of inflammatory diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, plaque psoriasis, inflammatory bowel disease, hidradenitis suppurativa, and refractory asthma.
Kits for administration concepts, including subcutaneous administration and kits comprising instructions and injection device concepts.
Interested in licensing this patent?