Methods of treatment with stable liquid formulations of glucagon-like peptide 1 or analogues thereof
Inventors
HAWE, Andrea • KEILHAUER, Eva • POPKO, Olimpia • Kenny, Enda • Warburg, Richard
Assignees
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Publication Number
US-11980655-B2
Publication Date
2024-05-14
Expiration Date
Abstract
Stable liquid formulations of GLP-1 and GLP-1 analogues and method of using such formulations in the treatment of disorders or conditions are provided.
Core Innovation
Stable, aqueous liquid pharmaceutical formulations for GLP-1 and GLP-1-analogue treatment are provided. The formulations comprise a GLP-1 analogue having an amino acid sequence as set forth in SEQ ID NO:3 in defined concentration ranges, together with specific buffering, tonicity, and excipient components.
The formulations are designed to maintain a defined pH and to provide protection from aggregation/degradation. A histidine-HCl buffer and a pH between 6.5±0.15 and 7.5±0.15 are used in combination with tonicity agents such as mannitol or sucrose and a non-ionic surfactant polysorbate 20, together with optional amino acid excipients such as methionine.
The disclosed liquid formulations are presented as suitable for treating disorders where administration of a GLP-1 or a GLP-1 analogue is indicated. The document further ties the formulation to specific disorder indications, including irritable bowel syndrome subtypes (IBS-C and IBS-D) and a broader list including metabolic, cardiovascular, and neurodegenerative disorders.
Claims Coverage
The independent claims center on treating a disorder where GLP-1 administration is indicated by administering a liquid pharmaceutical formulation containing a GLP-1 analogue with SEQ ID NO:3. The claim coverage includes exemplar excipient compositions and a broader pH-defined formulation, with histidine-based buffering, a sugar-based tonicity agent, polysorbate 20, and an amino acid excipient.
Liquid formulation with SEQ ID NO:3 GLP-1 analogue at defined concentration plus histidine-HCl, tonicity agent, methionine, and polysorbate 20
Administering to a subject a liquid pharmaceutical formulation comprising a GLP-1 analogue having an amino acid sequence as set forth in SEQ ID NO:3 at a concentration from 100 μg/ml to 1 mg/ml, and comprising histidine-HCl at 10 mM with mannitol at 275 mM or sucrose at 233 mM (8%), methionine at 10 mM, and polysorbate 20 at 0.02%.
Liquid formulation buffered to pH 6.5±0.5 to 7.5±0.5 with histidine HCl, sugar tonicity agent, polysorbate 20, and amino acid excipient
Administering to a subject a liquid pharmaceutical formulation comprising a GLP-1 analogue having the amino acid sequence set forth in SEQ ID NO:3, wherein the liquid pharmaceutical formulation is at a pH between 6.5±0.5 and 7.5±0.5 and comprises histidine HCl (about 10 mM±10%), a sugar-based tonicity agent (100 mM to 450 mM), polysorbate 20 (0.005 to 0.05%), and an amino acid excipient (5 mM to 75 mM).
Across the independent claims, the coverage centers on administering a liquid pharmaceutical formulation containing a GLP-1 analogue with SEQ ID NO:3, using a histidine-based buffered system at a specified pH and histidine-HCl concentration, a defined sugar-based tonicity agent, and polysorbate 20, with an amino acid excipient such as methionine included in defined concentrations.
Stated Advantages
Stability of the liquid formulation is supported by analytical endpoints used to support monomer and aggregate specifications under stress conditions.
Long-term storage stability, including months/1 year under refrigerated or room temperature.
Stability under freeze-thaw and mechanical stress.
Low subvisible particle/aggregate content metrics.
Protection from aggregation/degradation.
Documented Applications
Treating a disorder or condition in which administration of a GLP-1 or a GLP-1 analogue is indicated, including the enumerated disorders: diabetes; ischemia; reperfused tissue injury; dyslipidemia; diabetic cardiomyopathy; myocardial infarction; acute coronary syndrome; obesity; catabolic changes after surgery; hyperglycemia; stroke; neurodegenerative disorders; memory and learning disorders; islet cell transplant; functional dyspepsia; and a disorder requiring regenerative therapy.
Treating irritable bowel syndrome (IBS), including constipation predominant IBS (IBS-C) and diarrhea predominant IBS (IBS-D).
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