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Publication Number
US-12337199-B2
Publication Date
2025-06-24
Expiration Date
Abstract
The present disclosure provides stable pharmaceutical formulations comprising a human antibody that specifically binds to Ebola Virus (EBOV). In certain embodiments, the formulations contain, in addition to an anti-EBOV antibody, a buffer, an amino acid, a non-ionic surfactant, and a stabilizer. The pharmaceutical formulations of the present disclosure exhibit a substantial degree of antibody stability upon stress, for example, agitation during transport, and storage, for example, storage at temperatures greater than 40° C.
Core Innovation
The invention relates to a stable liquid pharmaceutical formulation for an antibody that binds specifically to Ebola virus (EBOV). The formulation includes sucrose, a buffer comprising histidine, and an organic cosolvent comprising polysorbate, and it is defined to have a pH of 6.0 to 6.3. The formulation includes at least one EBOV-binding antibody with three heavy chain complementarity determining regions and three light chain complementarity determining regions contained in a selected heavy chain variable region/light chain variable region amino acid sequence pair, including specified combinations of three antibodies in some embodiments.
The formulation is further defined by maintaining ADCC potency of at least about 90% in an ADCC bioassay and/or demonstrating that at least 90% of the antibody is the native species after storage at about 40°C to about 45°C for no less than 20 days. The described development includes stability and aggregation-related assessment, identification of degradation pathways such as high molecular weight and low molecular weight species and acidic charge variants, and selection of histidine buffer with sucrose and polysorbate. The overall described approach supports a stable liquid presentation and performance over defined storage and in-use scenarios.
The stable liquid is described for compatible preparation and administration, including in-use stability for diluted formulations in PVC or polyethylene IV bags and sets with diluents such as 0.9% NaCl, 5% dextrose, and Lactated Ringer's. The document also includes individually formulated antibodies and a 1:1:1 three-antibody co-formulated drug product/OP. The disclosed formulations are grounded in experimental stability assessment for EBOV-binding antibody formulations.
Claims Coverage
Independent claims are clm-00001, clm-00035, and clm-00056. Across these independent claims, the inventive features include a specific composition of sucrose, histidine buffer, and polysorbate; defined EBOV-binding antibodies characterized by heavy and light chain CDR content and selected HCVR/LCVR sequence pairs; and stability performance requirements including pH and ADCC/native-species retention after storage at 40–45°C for at least 20 days.
Sucrose, histidine buffer, and polysorbate at pH 6.0 to 6.3
A stable liquid pharmaceutical formulation comprising sucrose, a buffer comprising histidine, and an organic cosolvent comprising polysorbate, wherein the formulation has a pH of 6.0 to 6.3.
Sequence-defined EBOV-binding antibodies
At least one antibody which binds specifically to EBOV and comprises three heavy chain CDRs and three light chain CDRs contained in a selected HCVR/LCVR amino acid sequence pair, including specified first, second, and third antibodies in some embodiments.
ADCC potency and native-species retention after storage at 40–45°C
The formulation maintains ADCC potency of at least about 90% in an ADCC bioassay and/or demonstrates that at least 90% of the antibody is the native species after storage at a temperature from about 40°C to about 45°C for no less than 20 days.
Taken together, the independent claims require a stable liquid formulation with a sucrose/histidine/polysorbate system at pH 6.0 to 6.3, an EBOV-binding antibody defined by specific heavy and light chain CDRs contained in selected HCVR/LCVR sequence pairs, and formulation performance defined by ADCC potency and/or native species retention after elevated-temperature storage.
Stated Advantages
Maintains ADCC potency of at least about 90% in an ADCC bioassay.
Demonstrates at least 90% native species after storage at about 40°C to about 45°C for no less than 20 days.
Documented Applications
A stable liquid pharmaceutical formulation for EBOV-binding antibodies, including individually formulated antibodies and a 1:1:1 three-antibody co-formulated drug product/OP.
The pharmaceutical formulation is described for intravenous administration, including dilution prior to intravenous administration using PVC intravenous bags containing 0.9% sodium chloride, 5% dextrose, or Lactated Ringer's.
The document describes that one or more specified administration routes include intravenous, intramuscular, subcutaneous, intraperitoneal, percutaneous, mucosal, nasal, pulmonary, and oral administration.
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