Protein formulations for use at elevated temperatures
View Patent ↗Liquid formulations of bone morphogenetic proteins are provided for prolonged use at elevated temperatures. More specifically, the invention relates to liquid formulations comprising rhGDF-5, trehalose, and one or more biocompatible excipients that provide stability to the protein for at least 30 days at temperatures up to body temperature.
1. A composition comprising GDF-5 and excipients in an acidic solution, wherein the excipients are trehalose, present in the amount of 60% w/v, an amino acid, and a trialkylammonium salt.
2. The composition of claim 1 wherein the amino acid is selected from the group consisting of β-alanine, L-glycine, and L-proline.
3. The composition of claim 2 wherein the amino acid is comprised of β-alanine present in an amount of from about 0.25% to about 5% w/v.
4. The composition of claim 3 wherein the β-alanine is present in an amount of about 0.5% w/v.
5. The composition of claim 1 wherein the trialkylammonium salt is present in an amount of from about 0.1% to about 3% w/v.
6. The composition of claim 5 wherein the trialkylammonium salt is triethylammonium hydrochloride.
7. The composition of claim 1 wherein the amino acid is present in an amount of from about 0.25% to about 5% w/v and the trialkylammonium salt is present in an amount of from about 0.1% to about 3% w/v.
8. The composition of claim 7 wherein the amino acid is β-alanine present in an amount of about 0.5% w/v and the trialkylammonium salt is triethylammonium hydrochloride present in an amount of about 0.1% w/v.
9. The composition of claim 1 further comprising the heat shock protein HSP 70 present in an amount of from about 0.1% to 0.2% w/v.
10. The composition of claim 1 further comprising β-alanine present in an amount of about 0.5% w/v and taurine present in an amount of about 0.1% w/v.
11. The composition of claim 1 further comprising a betaine present in an amount of about 0.5% w/v.
12. A method for stabilizing a GDF-5 solution comprising providing GDF-5 in an acidic solution, adding an amount of trehalose to provide 60% w/v solution of trehalose, and adding an amino acid, and a trialkylammonium salt.