Use of C-type natriuretic peptide variants to treat skeletal dysplasia
AssigneeBiomarin Pharmaceutical Inc.
InventorsSherry Bullens, Stuart Bunting, Tianwei Chou, Augustus O. Okhamafe, Christopher P. Price, Daniel J. Wendt, Clarence Yap
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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.
Claims19
A kit comprising,
- a composition comprising a CNP variant peptide selected from the group consisting of:
- [CNP-37(M32N);
- SEQ ID NO:
- 1]
- QEHPNARKYKGANKKGLSKGCFGLKLDRIGSNSGLGC;
- (Met-CNP-37;
- SEQ ID NO:
- 2)
- MQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- (Pro-CNP-37;
- SEQ ID NO:
- 3)
- PQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- [Gly-CNP-37(M32N);
- SEQ ID NO:
- 4]
- GQEHPNARKYKGANKKGLSKGCFGLKLDRIGSNSGLGC;
- (Pro-Gly-CNP-37;
- SEQ ID NO:
- 5)
- PGQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- (Met-Gly-CNP-37;
- SEQ ID NO:
- 6)
- MGQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- and
- (Gly-CNP-37 or CNP-38;
- SEQ ID NO:
- 7)
- GQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC,
- wherein said CNP variant peptide is in a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine, and polysorbate 80, and wherein the composition is lyophilized in a vial;
- and instructions for use.
A method of treating skeletal dysplasia in a subject comprising the step of administering to said subject a composition comprising a CNP variant peptide in an amount of at least 7.5 μg/kg of said CNP variant peptide, wherein said CNP variant peptide is selected from the group consisting of:
- [CNP-37(M32N);
- SEQ ID NO:
- 1]
- QEHPNARKYKGANKKGLSKGCFGLKLDRIGSNSGLGC;
- (Met-CNP-37;
- SEQ ID NO:
- 2)
- MQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- (Pro-CNP-37;
- SEQ ID NO:
- 3)
- PQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- [Gly-CNP-37(M32N);
- SEQ ID NO:
- 4]
- GQEHPNARKYKGANKKGLSKGCFGLKLDRIGSNSGLGC;
- (Pro-Gly-CNP-37;
- SEQ ID NO:
- 5)
- PGQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- (Met-Gly-CNP-37;
- SEQ ID NO:
- 6)
- MGQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- and
- (Gly-CNP-37 or CNP-38;
- SEQ ID NO:
- 7)
- GQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC,
- wherein said CNP variant peptide is in a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine, and polysorbate 80;
- wherein said composition comprises about 0.5 mq/ml to about 2.0 mg/ml of said CNP peptide variant;
- and
- wherein said step of administering treats said skeletal dysplasia in said subject.
A method of increasing long bone growth in a subject in need thereof, said method comprising the step of administering to said subject a composition comprising a CNP variant peptide in an amount of at least 7.5 μg/kg of said CNP variant peptide, wherein said CNP variant peptide is selected from the group consisting of:
- [CNP-37(M32N);
- SEQ ID NO:
- 1]
- QEHPNARKYKGANKKGLSKGCFGLKLDRIGSNSGLGC;
- (Met-CNP-37;
- SEQ ID NO:
- 2)
- MQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- (Pro-CNP-37;
- SEQ ID NO:
- 3)
- PQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- [Gly-CNP-37(M32N);
- SEQ ID NO:
- 4]
- GQEHPNARKYKGANKKGLSKGCFGLKLDRIGSNSGLGC;
- (Pro-Gly-CNP-37;
- SEQ ID NO:
- 5)
- PGQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- (Met-Gly-CNP-37;
- SEQ ID NO:
- 6)
- MGQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- and
- (Gly-CNP-37 or CNP-38;
- SEQ ID NO:
- 7)
- GQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC,
- wherein said CNP variant peptide is in a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine, and polysorbate 80;
- wherein said composition comprises about 0.5 mq/ml to about 2.0 mq/ml of said CNP peptide variant;
- and
- wherein said step of administering increases long bone growth in said subject.
A method of increasing growth velocity in a subject in need thereof, said method comprising the step of administering a composition comprising a CNP variant peptide to said subject in an amount of at least 7.5 μg/kg, wherein said CNP variant peptide is selected from the group consisting of:
- [CNP-37(M32N);
- SEQ ID NO:
- 1]
- QEHPNARKYKGANKKGLSKGCFGLKLDRIGSNSGLGC;
- (Met-CNP-37;
- SEQ ID NO:
- 2)
- MQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- (Pro-CNP-37;
- SEQ ID NO:
- 3)
- PQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- [Gly-CNP-37(M32N);
- SEQ ID NO:
- 4]
- GQEHPNARKYKGANKKGLSKGCFGLKLDRIGSNSGLGC;
- (Pro-Gly-CNP-37;
- SEQ ID NO:
- 5)
- PGQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- (Met-Gly-CNP-37;
- SEQ ID NO:
- 6)
- MGQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- and
- (Gly-CNP-37 or CNP-38;
- SEQ ID NO:
- 7)
- GQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC,
- wherein said CNP variant peptide is in a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine, and polysorbate 80;
- wherein said composition comprises about 0.5 mq/ml to about 2.0 mq/ml of said CNP peptide variant;
- and
- wherein said step of administering increases growth velocity in said subject.
A method of treating skeletal dysplasia in a subject comprising the step of administering to said subject a composition comprising a CNP variant peptide in an amount of at least 7.5 μg/kg of said CNP variant peptide, wherein said CNP variant peptide is selected from the group consisting of:
- [CNP-37(M32N);
- SEQ ID NO:
- 1]
- QEHPNARKYKGANKKGLSKGCFGLKLDRIGSNSGLGC;
- (Met-CNP-37;
- SEQ ID NO:
- 2)
- MQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- (Pro-CNP-37;
- SEQ ID NO:
- 3)
- PQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- [Gly-CNP-37(M32N);
- SEQ ID NO:
- 4]
- GQEHPNARKYKGANKKGLSKGCFGLKLDRIGSNSGLGC;
- (Pro-Gly-CNP-37;
- SEQ ID NO:
- 5)
- PGQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- (Met-Gly-CNP-37;
- SEQ ID NO:
- 6)
- MGQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC;
- and
- (Gly-CNP-37 or CNP-38;
- SEQ ID NO:
- 7)
- GQEHPNARKYKGANKKGLSKGCFGLKLDRIGSMSGLGC,
- wherein said CNP variant peptide is in a formulation comprising citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, D-mannitol, L-methionine, and polysorbate 80;
- wherein said composition comprises about 10.0 mg/ml±9.9 mg/ml of said CNP peptide variant;
- and
- wherein said step of administering treats said skeletal dysplasia in said subject.
Dependencies are inferred from the claim text.