Use of C-type natriuretic peptide variants to treat skeletal dysplasia
Inventors
Bullens, Sherry • Bunting, Stuart • Chou, Tianwei • Okhamafe, Augustus O. • Price, Christopher P. • Wendt, Daniel J. • Yap, Clarence
Assignees
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Publication Number
US-11911446-B2
Publication Date
2024-02-27
Expiration Date
Abstract
The present disclosure provides for use of variants of C-type natriuretic peptide (CNP), and novel pharmaceutical compositions and formulations comprising CNP variant peptides for the treatment of skeletal dysplasias, one or more symptoms of skeletal dysplasias, such as long bone growth or growth velocity, and other disorders having a skeletal dysplasia and/or CNP-associated symptom or component.
Core Innovation
The invention provides a method of increasing long bone growth in a subject in need thereof by administering a composition comprising a CNP variant peptide in an amount of at least 7.5 μg/kg. The CNP variant peptide is selected from CNP-37(M32N), Met-CNP-37, Pro-CNP-37, Gly-CNP-37(M32N), Pro-Gly-CNP-37, Met-Gly-CNP-37, and Gly-CNP-37 or CNP-28, and the composition comprises citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80.
The described approach is also directed to increasing growth velocity in a subject in need thereof by administering a composition comprising the same CNP variant peptide selection and an amount of at least 7.5 μg/kg. The step of administering increases growth velocity in the subject, and the document reports clinical outcomes related to annualized standing-height growth velocity and safety observations in achondroplasia.
Claims Coverage
The partial content contains two independent claims: one focused on increasing long bone growth and one focused on increasing growth velocity. Both recite administration of a CNP variant peptide composition at an amount of at least 7.5 μg/kg together with citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80.
CNP variant peptide composition for increasing long bone growth
A method of increasing long bone growth in a subject in need thereof by administering a composition comprising a CNP variant peptide in an amount of at least 7.5 μg/kg, wherein the CNP variant peptide is selected from CNP-37(M32N), Met-CNP-37, Pro-CNP-37, Gly-CNP-37(M32N), Pro-Gly-CNP-37, Met-Gly-CNP-37, and Gly-CNP-37 or CNP-28, and wherein the composition comprises citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80.
CNP variant peptide composition for increasing growth velocity
A method of increasing growth velocity in a subject in need thereof by administering a composition comprising a CNP variant peptide in an amount of at least 7.5 μg/kg, wherein the CNP variant peptide is selected from CNP-37(M32N), Met-CNP-37, Pro-CNP-37, Gly-CNP-37(M32N), Pro-Gly-CNP-37, Met-Gly-CNP-37, and Gly-CNP-37 or CNP-38, and wherein the composition comprises citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80.
Both independent claims are directed to methods that administer a composition containing a specified CNP variant peptide at an amount of at least 7.5 μg/kg together with citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine and polysorbate 80, where administration increases either long bone growth or growth velocity.
Stated Advantages
Increasing long bone growth in a subject in need thereof.
Increasing growth velocity in a subject in need thereof.
In achondroplasia, statistically significant increases in annualized standing-height growth velocity at 7.5 μg/kg/day and 15 μg/kg/day over 6 months, with additional 12-month efficacy at 15 μg/kg/day.
Safety outcomes reported as no grade 2 or higher adverse events related to the drug and no clinically significant changes in specified blood safety biomarkers.
Documented Applications
Treatment of skeletal dysplasias, especially achondroplasia, to increase long-bone growth and growth velocity.
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