Stabilized formulations containing anti-interleukin-4 receptor (IL-4R) antibodies
The present invention provides pharmaceutical formulations comprising a human antibody that specifically binds to human interleukin-4 receptor (hIL-4R). The formulations may contain, in addition to an anti-hIL-4R antibody, at least one amino acid, at least one sugar, or at least one non-ionic surfactant. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability after storage for several months.
1 . A pharmaceutical formulation comprising:
(i) an anti-human interleukin-4 receptor alpha (anti-hIL4Rα) antibody at a concentration of about 100 mg/ml to about 200 mg/ml, wherein the anti-hIL4Rα antibody is a human antibody, wherein the anti-hIL4Rα antibody is an immunoglobulin molecule comprising two heavy chains and two light chains interconnected by disulfide bonds, wherein each heavy chain comprises a heavy chain variable region (HCVR), wherein the HCVR comprises the amino acid sequence of SEQ ID NO: 1, wherein each light chain comprises a light chain variable region (LCVR), wherein the LCVR comprises the amino acid sequence of SEQ ID NO: 5;
(ii) a thermal stabilizer at a concentration from about 0.9%±0.135% w/v to about 10%±1.5% w/v;
(iii) a non-ionic surfactant; and
(iv) arginine at a concentration from about 20 to 100 mM;
wherein the pharmaceutical formulation has a pH from about 5.6 to about 6.2;
wherein the viscosity of the pharmaceutical formulation is less than 35 cPoise; and
wherein less than about 5% of the anti-hIL4Rα antibody recovered from the pharmaceutical formulation after 3 months of storage at 5° C. is aggregated, as determined by size exclusion chromatography.
2 . The pharmaceutical formulation of claim 1 , wherein the non-ionic surfactant is a poloxamer or a polyethylene glycol.
3 . The pharmaceutical formulation of claim 2 , wherein the non-ionic surfactant is poloxamer 188.
4 . The pharmaceutical formulation of claim 1 , wherein the non-ionic surfactant is a polysorbate.
5 . The pharmaceutical formulation of claim 4 , wherein the polysorbate is polysorbate 20 or polysorbate 80.
6 . The pharmaceutical formulation of claim 5 , wherein the polysorbate 20 or polysorbate 80 is at a concentration of about 0.2% w/v.
7 . The pharmaceutical formulation of claim 5 , wherein the pharmaceutical formulation has a pH of about 5.9.
8 . The pharmaceutical formulation of claim 5 , wherein the anti-hIL4Rα antibody is at a concentration of about 175 mg/mL.
9 . The pharmaceutical formulation of claim 8 , wherein the arginine is at a concentration of about 50 mM±7.5 mM.
10 . The pharmaceutical formulation of claim 5 , wherein the anti-hIL4Rα antibody is at a concentration of about 150 mg/mL.
11 . The pharmaceutical formulation of claim 10 , wherein the arginine is at a concentration of about 50 mM±7.5 mM.
12 . The pharmaceutical formulation of claim 1 , wherein the pharmaceutical formulation has an osmolality of less than about 450 mOsm/kg.
13 . The pharmaceutical formulation of claim 1 , wherein the thermal stabilizer is a sugar or a sugar alcohol at a concentration from about 2.5% w/v to about 10% w/v.
14 . The pharmaceutical formulation of claim 13 , wherein the sugar or sugar alcohol is sucrose, sorbitol, mannitol, or trehalose.
15 . The pharmaceutical formulation of claim 14 , wherein the sugar or sugar alcohol is sucrose.
16 . The pharmaceutical formulation of claim 15 , wherein the sucrose is at a concentration of about 5%±0.75% w/v.
17 . The pharmaceutical formulation of claim 15 , wherein the sucrose is at a concentration of about 5.5%±0.825% w/v.
18 . The pharmaceutical formulation of claim 14 , wherein the pharmaceutical formulation has an osmolality of less than about 450 mOsm/kg.
19 . The pharmaceutical formulation of claim 14 , wherein the non-ionic surfactant is a poloxamer or a polyethylene glycol.
20 . The pharmaceutical formulation of claim 19 , wherein the non-ionic surfactant is poloxamer 188.
21 . The pharmaceutical formulation of claim 14 , wherein the non-ionic surfactant is a polysorbate.
22 . The pharmaceutical formulation of claim 21 , wherein the polysorbate is polysorbate 20 or polysorbate 80.
23 . The pharmaceutical formulation of claim 22 , wherein the polysorbate 20 or polysorbate 80 is at a concentration of about 0.2% w/v.
24 . The pharmaceutical formulation of claim 23 , wherein the pharmaceutical formulation has a pH of about 5.9.
25 . The pharmaceutical formulation of claim 22 , wherein the anti-hIL4Rα antibody is at a concentration of about 175 mg/mL.
26 . The pharmaceutical formulation of claim 25 , wherein the arginine is at a concentration of about 50 mM±7.5 mM.
27 . The pharmaceutical formulation of claim 25 , wherein the non-ionic surfactant is polysorbate 80, and wherein the polysorbate 80 is at a concentration of about 0.2% w/v.
28 . The pharmaceutical formulation of claim 22 , wherein the anti-hIL4Rα antibody is at a concentration of about 150 mg/mL.
29 . The pharmaceutical formulation of claim 28 , wherein the arginine is at a concentration of about 50 mM±7.5 mM.
30 . The pharmaceutical formulation of claim 28 , wherein the non-ionic surfactant is polysorbate 80, and wherein the polysorbate 80 is at a concentration of about 0.2% w/v.