VEGFR fusion protein pharmaceutical composition
Inventors
Nguyen, Tan • Wu, Pei-Tzu • Chang, Yung-Sheng • CHERUKURY, Madhu
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11723955-B1
Publication Date
2023-08-15
Expiration Date
Abstract
The present invention relates to a biologic that inhibits angiogenesis. In particular, the present invention relates to fusion proteins that inhibit the integrin activated pathway and one other angiogenic factor-activated pathway as well as formulation compositions of such fusion proteins, as well as methods for producing and using the same.
Core Innovation
The disclosed invention relates to a pharmaceutical formulation comprising a VEGFR-integrin-targeting Fc fusion protein composition. The formulation includes a fusion protein at a specified concentration in combination with defined buffer and stabilizing excipients, and the formulation is adjusted to a pH of about 6.0. The fusion protein is provided as an amino acid sequence selected from SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, or SEQ ID NO:18.
The formulation uses histidine as a buffer component at 25 mM, together with trehalose or mannitol at 190 mM, and includes 0.03% polysorbate 20 or polysorbate 80. The disclosed approach is focused on maintaining fusion protein stability and performance, including purity/potency retention and storage stability at low temperatures.
The patent also documents anti-angiogenesis and anti-fibrotic activity associated with the VEGFR-integrin-targeting Fc fusion protein. In vivo and model data are described as showing reduced vascular leakage, reduced retinal thickness changes, and reduced fibrosis marker changes in choroidal neovascularization and bleomycin-induced lung fibrosis contexts.
Claims Coverage
The independent claim covers a pharmaceutical formulation defined by a fusion protein sequence selection, a specified fusion protein concentration, defined buffer and stabilizing excipients, and a pH of about 6.0. The inventive feature set totals one independent inventive claim, with dependent claims refining stability/performance constraints and enumerating optional additional excipients.
Pharmaceutical formulation with VEGFR-integrin-targeting Fc fusion protein at defined excipient composition and pH
A pharmaceutical formulation comprising a fusion protein in a concentration of 40 mg/mL, wherein the fusion protein comprises the amino acid sequence of SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, or SEQ ID NO:18; 25 mM histidine; 190 mM trehalose or mannitol; 0.03% polysorbate 20 or polysorbate 80; wherein the formulation is at a pH of about 6.0.
Across the claim set, the core coverage is the defined VEGFR-integrin-targeting Fc fusion protein formulation (sequence-selected fusion protein at 40 mg/mL) combined with histidine, trehalose or mannitol, and polysorbate at 0.03% at pH about 6.0, with dependent claims further requiring specified storage stability and additional salt/amino-acid options.
Stated Advantages
Improved storage stability at low temperatures.
Retention of protein purity and potency after specified storage conditions.
Maintained SEC-HPLC purity and binding potency in pilot drug product stability data.
Reduced vascular leakage and reduced retinal thickness/fibrosis marker changes in documented disease-model studies.
Reduced fibrosis marker (hydroxyproline) in a documented bleomycin-induced lung fibrosis context.
Documented Applications
Treatment or modulation of choroidal neovascularization (CNV) in a rhesus laser-induced CNV context, described with reduced vascular leakage and retinal thickness/fibrosis marker outcomes.
Anti-fibrotic application in a bleomycin-induced lung fibrosis model, described with reduced hydroxyproline.
Retinal leakage assessment in a rabbit VEGF-A165 retinal leakage study, described with reduced leakage scores.
Interested in licensing this patent?