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US 2022/0016211 A1Published application
Fgf-21 conjugate formulations
AssigneeBristol-Myers Squibb Company
InventorsThomas PALM, Mehrnaz KHOSSRAVI, Sanket PATKE
Life of this patent
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Abstract
The present application provides pharmaceutical formulations comprising PEGylated FGF-21, e.g., a FGF-21 conjugate, and one or more stabilizers such as the chelator DPTA. The formulations can be can further stabilized by including a surfactant such as polysorbate 80 and/or adjusting the pH to about 7.1. Also provided are methods of manufacture, methods of treatment, and kits.
Claims29
1-111. (canceled)
A pharmaceutical formulation comprising
- (i) a fibroblast growth factor 21 (FGF-21) polypeptide comprising an amino acid sequence having at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, or at least about 99% amino acid sequence identity to the amino acid sequence of SEQ ID NO:
- 3, conjugated to a polyethylene glycol (PEG) moiety via the side chain of an amino acid in the amino acid sequence (“FGF-21 conjugate”);
- and,
- (ii) an aminopolycarboxylic acid cation chelator comprising diethylenetriaminepentaacetic acid (DTPA),
- wherein the formulation has improved stability compared to a reference formulation that does not contain the aminopolycarboxylic acid cation chelator,
- wherein the FGF-21 conjugate comprises formula I:
- wherein n is an integer from about 500 to about 900, and
- wherein the FGF-21 conjugate is present in an amount between about 1 mg and about 40 mg per unit dose.
5 more elements
A pharmaceutical composition comprising:
- (i) a FGF-21 conjugate corresponding to a compound of SEQ ID NO:
- 2, 4, 5 or 6 at a concentration of 20 mg/mL as measured by Slope Spectroscopy at 280 nm using an extinction coefficient of 0.87 mL/(mg*cm);
- (ii) histidine at a concentration between about 10 mM and about 50 mM;
- (iii) sucrose at a concentration between about 100 mM and about 1M;
- (iv) Polysorbate 80 at a concentration between about 0.01% and about 0.1% (w/v);
- and,
- (v) DTPA at a concentration between about 10 μM and about 100 μM;
- wherein the pH of the formulation is between about 6.7 and about 7.5, and
- wherein the FGF-21 conjugate is present in an amount between about 1 mg and about 40 mg per unit dose.
6 more elements
A pharmaceutical formulation comprising:
- (i) a FGF-21 conjugate corresponding to a compound of SEQ ID NO:
- 2, 4, 5 or 6 at a concentration of 20 mg/mL as measured by Slope Spectroscopy at 280 nm using an extinction coefficient of 0.87 mL/(mg*cm);
- (ii) histidine at a concentration of 20 mM;
- (iii) sucrose at a concentration of 600 mM;
- (iv) Polysorbate 80 at a concentration of 0.05% (w/v);
- and
- (v) DTPA at a concentration of 50 uM;
- wherein the pH is 7.1,
- wherein the FGF-21 conjugate is present in an amount between about 1 mg and about 40 mg per unit dose.
6 more elements
A vial comprising:
- (i) a FGF-21 conjugate corresponding to a compound of SEQ ID NO:
- 2, 4, 5 or 6 at a concentration of 20 mg/mL as measured by Slope Spectroscopy at 280 nm using an extinction coefficient of 0.87 mL/(mg*cm);
- (ii) histidine at a concentration between about 10 mM and about 50 mM;
- (iii) sucrose at a concentration between about 100 mM and about 1M;
- (iv) Polysorbate 80 at a concentration between about 0.01% and about 0.1% (w/v);
- and,
- (v) DTPA at a concentration between about 10 μM and about 100 μM;
- wherein the pH is between about 6.7 and about 7.5, and
- wherein the FGF-21 conjugate is present in an amount between about 1 mg and about 40 mg per unit dose.
6 more elements
A vial comprising:
- (i) a FGF-21 conjugate corresponding to a compound of SEQ ID NO:
- 2, 4, 5 or 6 at a concentration of 20 mg/mL as measured by Slope Spectroscopy at 280 nm using an extinction coefficient of 0.87 mL/(mg*cm);
- (ii) histidine at a concentration of 20 mM;
- (iii) sucrose at a concentration of 600 mM;
- (iv) Polysorbate 80 at a concentration of 0.05% (w/v);
- and
- (v) DTPA at a concentration of 50 uM;
- wherein the pH is 7.1, and
- wherein the FGF-21 conjugate is present in an amount between about 1 mg and about 40 mg per unit dose.
6 more elements
Dependencies are inferred from the claim text.