Liquid formulations of anti-CD200 antibodies
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Publication Number
US-12139533-B2
Publication Date
2024-11-12
Expiration Date
Abstract
The present disclosure provides stable liquid pharmaceutical formulations comprising anti-CD200 antibodies or antigen-binding fragments thereof, and articles of manufacture and kits containing the formulations. Also featured are methods of using the formulations in cancer and autoimmune therapies, and for preventing, delaying or treating cell, tissue, or organ transplant rejection.
Core Innovation
The document discloses a liquid pharmaceutical formulation comprising an anti-CD200 antibody or an antigen binding fragment thereof, including an embodiment having light chain variable region and heavy chain variable region sequences set forth in SEQ ID NO:11 and SEQ ID NO:10. The formulation is characterized by specific excipients and buffer components, including mannitol, polysorbate, citrate buffer at an about pH of 5.0 to 6, and NaCl, together with a defined antibody concentration and an osmolality of less than 525 mOsm/kg.
A key theme described is the use of citrate-buffered formulations with a citrate-buffer pH in the range of about 5.0 to about 5.6, together with mannitol and polysorbate, and a defined NaCl tonicity level. The document also describes acetate-buffered alternatives that can include neutral amino acids such as glycine and polysorbate, as part of the overall formulation approach.
The formulation stability is supported using analytical assays including GP-HPLC/SEC-HPLC, SDS-PAGE, IEF, and subvisible particle counts, with additional measurements reported such as osmolality and aggregation/precipitation observations. The document reports preserved monomer levels and low aggregation/precipitation, and it also describes compatibility for IV administration, including container/tubing compatibility and dilution in saline within the stated time window and temperature conditions [procedural detail omitted for safety].
Claims Coverage
The partial content provides one independent claim (clm-00001). The inventive features relate to a specific liquid pharmaceutical composition defined by antibody/fragment identity, excipient selection and concentrations, buffer pH and tonicity, and performance constraints for osmolality and long-term stability at 2–8°C.
Anti-CD200 antibody or antigen-binding fragment with specified variable region sequences
An anti-CD200 antibody or antigen binding fragment thereof at a concentration of between about 5 to 10 mg/mL, wherein the anti-CD200 antibody or antigen binding fragment comprises a light chain variable region comprising the sequence set forth in SEQ ID NO:11 and a heavy chain variable region comprising the sequence set forth in SEQ ID NO:10.
Mannitol and polysorbate excipients at defined amounts
About 1 to 3% mannitol and about 0.02% polysorbate.
Citrate buffer at about pH 5.0–6 and defined NaCl tonicity
About 50 mM citrate buffer at a pH of about 5.0 to about 6, and about 75 to 150 mM NaCl.
Osmolality limit and long-term stability at 2–8°C
The formulation has an osmolality of less than 525 mOsm/kg and is stable at 2–8°C for a period of at least 9 months.
Overall, the claim coverage centers on a narrowly defined liquid pharmaceutical formulation for an anti-CD200 antibody/fragment defined by specified SEQ ID variable regions, formulated with mannitol and a low amount of polysorbate, buffered by citrate at pH about 5.0–6 with specified NaCl tonicity, and meeting an osmolality ceiling and stability requirement at 2–8°C for at least 9 months.
Stated Advantages
The formulation has osmolality of less than 525 mOsm/kg.
The formulation is stable at 2–8°C for at least 9 months.
The document reports preserved monomer levels and low aggregation/precipitation after extended storage, including up to 24 months.
The document reports an osmolality improvement versus an earlier histidine/glycine buffered samalizumab formulation.
Documented Applications
Therapeutic use areas described include cancer therapy.
Therapeutic use areas described include autoimmune disorders.
Therapeutic use areas described include transplant rejection and GVHD prevention.
The document provides formulation stability/compatibility context for IV administration, including container/tubing compatibility and dilution in saline within the stated time window and temperature conditions [procedural detail omitted for safety].
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