Stable liquid formulations of glucagon-like peptide 1 or analogues thereof
Inventors
HAWE, Andrea • KEILHAUER, Eva • POPKO, Olimpia • Kenny, Enda • Warburg, Richard
Assignees
Coriolis Pharma Research GmbH • Metaphase Ltd • Rose Pharma Inc
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11058748-B2
Publication Date
2021-07-13
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
The invention relates to stable aqueous liquid pharmaceutical formulations comprising a GLP-1 analogue consisting of the amino acid sequence set forth in SEQ ID NO:3. The formulations are characterized by a specified peptide concentration range and a formulation pH range, and they comprise histidine HCl, a sugar-based tonicity agent, and polysorbate 20.
The formulations comprise histidine HCl as a buffering agent, together with a sugar-based tonicity agent and polysorbate 20. The tonicity agent can be mannitol or sucrose, and optional amino acid excipients include methionine or proline. The buffering and tonicity components establish a desired pH and near-isotonic osmolality, while polysorbate 20 is used as a non-ionic surfactant.
The disclosed formulations are described with stability assessment criteria addressing aggregation and degradation outcomes, including monomer content, aggregate content, and subvisible particles reported by analytical methods such as HP-SEC and RP-UPLC. Stress conditions discussed include freeze-thaw, mechanical stress, elevated temperature, and long-term storage, and the document contemplates use of the formulation for disorders including irritable bowel syndrome, including IBS-C, IBS-D, and IBS-M.
Claims Coverage
The partial claim set includes two independent claims. The claim coverage centers on a liquid pharmaceutical formulation of a GLP-1 analogue defined by SEQ ID NO:3 at specified concentration and pH ranges, with histidine HCl, a sugar-based tonicity agent, and polysorbate 20, and the second independent claim further specifies mannitol or sucrose and optional methionine or proline.
Liquid pharmaceutical formulation with GLP-1 analogue (SEQ ID NO:3) at defined concentration, pH, and excipient system
A liquid pharmaceutical formulation comprising a GLP-1 analogue consisting of the amino acid sequence set forth in SEQ ID NO:3, wherein the GLP-1 analogue is at a concentration of 50 μg/ml to 2 mg/ml and wherein the liquid pharmaceutical formulation is at a pH of between 6.5±0.5 and 7.5±0.5 and comprises histidine HCl at about 10 mM±10%, a sugar-based tonicity agent at 100 mM to 450 mM, polysorbate 20 at 0.005 to 0.05%, and an amino acid excipient at 5 mM to 75 mM.
Liquid pharmaceutical formulation with defined histidine-HCl, mannitol or sucrose, polysorbate 20, and amino acid excipients
A liquid pharmaceutical formulation comprising a GLP-1 analogue consisting of an amino acid sequence as set forth in SEQ ID NO:3, wherein the GLP-1 analogue is at a concentration of from 50 μg/ml to 2 mg/ml and wherein the liquid pharmaceutical formulation is at a pH of between 6.5±0.5 and 7.5±0.5 and comprises histidine-HCl at about 10 mM±10% together with mannitol or sucrose within specified ranges or set points and polysorbate 20 at 0.01 to 0.03% w/v, with optional inclusion of methionine and/or proline within the stated ranges.
Across the independent claims, the core inventive concept is a liquid pharmaceutical formulation of a GLP-1 analogue defined by SEQ ID NO:3, formulated within specified peptide concentration and pH ranges, and comprising a defined histidine-HCl buffering component, a sugar-based tonicity agent, and polysorbate 20, with further limitations in the second independent claim that specify alternative excipient sub-compositions including mannitol or sucrose and optional amino acid excipients (methionine and/or proline).
Stated Advantages
Minimizes aggregation and degradation under stress conditions including freeze-thaw, mechanical stress, elevated temperature, and long-term storage.
Documented Applications
Use for disorders including irritable bowel syndrome (IBS), including IBS-C, IBS-D, and IBS-M.
Interested in licensing this patent?