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-12318428-B2
Publication Date
2025-06-03
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 invention relates to VEGFR/VEGF receptor-Fc fusion proteins that inhibit angiogenesis. The fusion proteins block an integrin-activated pathway and an additional angiogenic-factor-activated pathway, including a VEGF/VEGFR pathway associated with VEGF-A and VEGF-A165.
The document further provides a pharmaceutical formulation for the fusion protein. The formulation includes trehalose or mannitol, a buffering agent selected from sodium phosphate and histidine and other specified buffering agents, and a surfactant at a specified concentration, with the formulation adjusted to a pH of about 5.5-7.5. Optionally, the formulation further comprises a polysaccharide selected from specified materials.
Extensive preclinical and formulation-development data are described in support of the formulation. The document reports in vivo efficacy in laser-induced choroidal neovascularization (rhesus monkeys) and anti-fibrotic activity in bleomycin lung fibrosis (mice), and it also describes retinal vascular leakage in VEGF-A165-stimulated rabbits. Stability and quality studies are described as maintaining protein purity and protein potency with evaluation of aggregation and sub-visible particles under multiple storage and stress conditions.
Claims Coverage
The independent claims are directed to a pharmaceutical formulation containing VEGFR/VEGF receptor-Fc fusion proteins defined by SEQ ID NO:15-18, together with specified excipients and pH. Across the independent claims, the key inventive features can be grouped into the defined fusion protein sequences and the defined formulation system comprising trehalose or mannitol, a selected buffering agent, a selected surfactant system, an about 5.5-7.5 pH, and optional polysaccharide excipients.
Fusion protein defined by SEQ ID NO:15-SEQ ID NO:18
A pharmaceutical formulation comprising a fusion protein in a concentration of about 0.5 mg/mL to about 120 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.
Trehalose or mannitol excipient at about 25 mM to about 250 mM
A pharmaceutical formulation wherein trehalose or mannitol is present at a concentration of about 25 mM to about 250 mM.
Selected buffering agent at about 10 mM to about 50 mM
A pharmaceutical formulation wherein a buffering agent selected from sodium phosphate, histidine, sodium citrate, sodium acetate, sodium bicarbonate, and trisodium citrate dihydrate is present in a concentration of about 10 mM to about 50 mM.
Surfactant at about 0.01% to about 4% w/v with pH about 5.5-7.5
A pharmaceutical formulation wherein a surfactant is present at a concentration of about 0.01 to about 4% w/v, wherein the formulation is at a pH of about 5.5-7.5.
Optional polysaccharide excipient
Optionally, the formulation further comprises a polysaccharide selected from sodium carboxymethylcellulose, microcrystalline cellulose, or sodium hyaluronate.
Overall, the independent claims cover a pharmaceutical formulation centered on VEGFR/VEGF receptor-Fc fusion proteins (SEQ ID NO:15-18) combined with a defined cryo-/stabilizing excipient (trehalose or mannitol), a selected buffering agent system, and a surfactant system at a defined concentration range, formulated at pH about 5.5-7.5, with optional inclusion of selected polysaccharides.
Stated Advantages
Maintains protein purity and protein potency after specified storage conditions, including at least 6 months when stored at 2-8°C.
Maintains stability and quality of the fusion protein under multiple storage conditions and stress conditions, with evaluation of aggregation and sub-visible particles.
Documented Applications
In vivo efficacy in laser-induced choroidal neovascularization (rhesus monkeys).
Anti-fibrotic activity in bleomycin lung fibrosis (mice).
Retinal vascular leakage in VEGF-A165-stimulated rabbits.
Interested in licensing this patent?