Formulations for bovine granulocyte colony stimulating factor and variants thereof
This invention provides stable aqueous formulations comprising a bG-CSF polypeptide or a variant thereof, a buffer substance, and an excipient, wherein said formulation is substantially free of polyoxyethylene (20) sorbitan monolaurate. The invention also provides methods of using, a lyophilized or powdered form of, and processes for, preparing the formulation.
1. A stable aqueous formulation comprising
(a) a bovine granulocyte colony stimulating factor (bG-CSF) polypeptide of SEQ ID NO: 1 or SEQ ID NO: 2 comprising a non-naturally encoded amino acid substituted at position 133 of SEQ ID NO: 1 or the corresponding amino acid in SEQ ID NO: 2;
wherein the non-naturally encoded amino acid is para-acetylphenylalanine;
wherein said para-acetylphenylalanine is bonded to a water soluble polymer being a poly(ethylene) glycol moiety having a molecular weight of about 20 kDa;
(b) a citrate buffer;
(c) arginine, and optionally a counter ion for arginine;
(d) wherein said formulation contains less than 0.0033% of a surfactant; and
(e) wherein pH of the formulation ranges from 5.7 to 6.6.
2. The formulation of claim 1 wherein said surfactant is a polyoxyethylene derivative of sorbitan monolaurate.
3. The formulation of claim 2 wherein said surfactant is a polyoxyethylene (20) sorbitan monolaurate.
4. The formulation of claim 1 wherein the counter ion for arginine is chloride or sulfate.
5. The formulation of claim 1 optionally including one or more other therapeutic ingredients.
6. A lyophilisate or powder of the formulation of claim 1 .
7. A process for preparing the formulation of claim 1 comprising forming a stable aqueous solution comprising said bG-CSF polypeptide, a citrate buffer, arginine, and optionally a counter ion for arginine.
8. The formulation of claim 1 wherein said citrate buffer has a molarity of about 30 mM.
9. The formulation of claim 1 wherein said arginine has a molarity of about 250 mM.
10. The formulation of claim 8 wherein said arginine has a molarity of about 250 mM.
11. The formulation of claim 1 wherein the pH ranges from 6.0-6.3.
12. The formulation of claim 1 wherein the pH is 6.0±0.1.