Stable Aqueous Formulations of Natalizumab
Described herein is a stable aqueous pharmaceutical formulation comprising a therapeutically effective amount of natalizumab (optionally not subjected to prior lyophilization), a buffer effective to maintain the pH in the range from about 4.0 to about 7.0; and optionally, one or more surfactant{s), one or more amino acid(s), one or more sugar(s), one or more polyol(s), one or more chelating agent(s) (one or more polymer(s), one or more other stabilizing agent(s); and methods for making such a formulation; and methods of using such a formulation.
1 . An aqueous formulation comprising 20 mg/mL natalizumab and a buffer having a pH of between 4 and 7, wherein said buffer is not a phosphate buffer.
2 . The formulation of claim 1 , wherein said buffer is selected from the group consisting of acetate, succinate, citrate and histidine.
3 . The formulation of claim 2 , wherein said formulation further comprises a surfactant.
4 . The formulation of claim 5 , wherein said surfactant is selected from the group consisting of polysorbate 20 (PS-20), polysorbate 80 (PS-80) and n-Dodecyl-3-D-maltopyranoside (DDM).
5 . The formulation of claim 2 , comprising 20 mM acetate at pH 5.0, and wherein the formulation further comprises 0.02% PS-20.
6 . The formulation of claim 2 , comprising 20 mM succinate at pH 5.0, and wherein the formulation further comprises 0.02% P5-20.
7 . The formulation of claim 2 , comprising 20 mM citrate at pH 5.0, and wherein the formulation further comprises 0.02% PS-20.
8 . The formulation of claim 2 , comprising 20 mM histidine at pH 5.0, and wherein the formulation further comprises 0.02% PS-20.
9 . The formulation of claim 2 , comprising 20 mM acetate at pH 5.0, and wherein the formulation further comprises 0.1% DDM.
10 . The formulation of claim 2 , comprising 20 mM succinate at pH 5.0, and wherein the formulation further comprises 0.1% DDM.
11 . The formulation of claim 2 , comprising 20 mM citrate at pH 5.0, and wherein the formulation further comprises 0.1% DDM.
12 . The formulation of claim 2 , comprising 20 mM histidine at pH 5.0, and wherein the formulation further comprises 0.1% DDM.
13 . The formulation of claim 2 , comprising 20 mM acetate at pH 5.5, and wherein the formulation further comprises 0.02% PS-20.
14 . The formulation of claim 2 , comprising 20 mM succinate at pH 5.5, and wherein the formulation further comprises 0.02% PS-20.
15 . The formulation of claim 2 , comprising 20 mM citrate at pH 5.5, and wherein the formulation further comprises 0.02% PS-20.
16 . The formulation of claim 2 , comprising 20 mM histidine at pH 5.5, and wherein the formulation further comprises 0.02% P5-20.
17 . The formulation of claim 2 , comprising 20 mM acetate at pH 5.5, and wherein the formulation further comprises 0.1% DDM.
18 . The formulation of claim 2 , comprising 20 mM succinate at pH 5.5, and wherein the formulation further comprises 0.1% DDM.
19 . The formulation of claim 2 , comprising 20 mM citrate at pH 5.5, and wherein the formulation further comprises 0.1% DDM.
20 . The formulation of claim 2 , comprising 20 mM histidine at pH 5.5, and wherein the formulation further comprises 0.1% DDM.