Formulations of antibody molecules to dengue virus

Abstract

This disclosure relates to formulations of peptide agents, e.g., antibodies and antigen-binding fragments thereof, that bind dengue viruses, and methods of their use.

What is claimed is: 
     
         1 . A formulation comprising 10 mg/mL to 50 mg/mL of an anti-dengue antibody molecule, 10 mM to 50 mM histidine or sodium citrate, 50 mM to 150 mM sodium chloride, and 50 mM to 150 mM arginine or sucrose, wherein the formulation has a pH of 6 to 7, and wherein the antibody molecule comprises:
 (a) a heavy chain (HC) immunoglobulin variable region segment comprising:   an HC CDR1 comprising the sequence DVYMS (SEQ ID NO: 3),   an HC CDR2 comprising the sequence RIDPENGDTKYDPKLQG (SEQ ID NO: 4), and   an HC CDR3 comprising the sequence GWEGFAY (SEQ ID NO: 5); and   (b) a light chain (LC) immunoglobulin variable region segment comprising:   an LC CDR1 comprising the sequence RASENVDKYGNSFMH (SEQ ID NO: 6),   an LC CDR2 comprising the sequence RASELQW (SEQ ID NO: 7), and   an LC CDR3 comprising the sequence QRSNEVPWT (SEQ ID NO: 8).   
     
     
         2 . The formulation of  claim 1 , comprising 10 mg/mL to 40 mg/mL of the antibody molecule. 
     
     
         3 . The formulation of  claim 1 , comprising 25 mg/mL of the antibody molecule. 
     
     
         4 . The formulation of  claim 1 , comprising 10 mM to 50 mM histidine. 
     
     
         5 . The formulation of  claim 1 , comprising 20 mM to 40 mM histidine. 
     
     
         6 . The formulation of  claim 1 , comprising 25 mM histidine. 
     
     
         7 . The formulation of  claim 1 , comprising 10 mM to 50 mM sodium citrate. 
     
     
         8 . The formulation of  claim 1 , comprising 10 mM to 30 mM sodium citrate. 
     
     
         9 . The formulation of  claim 1 , comprising 25 mM sodium citrate. 
     
     
         10 . The formulation of  claim 1 , comprising 75 mM to 150 mM sodium chloride. 
     
     
         11 . The formulation of  claim 1 , comprising 75 mM sodium chloride. 
     
     
         12 . The formulation of  claim 1 , comprising 50 mM to 150 mM arginine. 
     
     
         13 . The formulation of  claim 1 , comprising 75 mM to 150 mM arginine. 
     
     
         14 . The formulation of  claim 1 , comprising 75 mM arginine. 
     
     
         15 . The formulation of  claim 1 , comprising 50 mM to 150 mM sucrose. 
     
     
         16 . The formulation of  claim 1 , comprising 75 mM to 100 mM sucrose. 
     
     
         17 . The formulation of  claim 1 , comprising 100 mM sucrose. 
     
     
         18 . The formulation of  claim 1 , which has a pH of 6.5. 
     
     
         19 . The formulation of  claim 1 , further comprising polysorbate 80. 
     
     
         20 . The formulation of  claim 1 , further comprising 0.01% to 0.05% polysorbate 80. 
     
     
         21 . The formulation of  claim 1 , further comprising 0.02% polysorbate 80. 
     
     
         22 . The formulation of  claim 1 , wherein the antibody molecule comprises the heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 1. 
     
     
         23 . The formulation of  claim 1 , wherein the antibody molecule comprises the light chain variable region (VL) amino acid sequence of SEQ ID NO: 2. 
     
     
         24 . The formulation of  claim 1 , wherein the antibody molecule comprises the VH amino acid sequence of SEQ ID NO: 1 and the VL amino acid sequence of SEQ ID NO: 2. 
     
     
         25 . The formulation of  claim 1 , comprising 10 mg/mL to 50 mg/mL of the antibody molecule, 10 mM to 50 mM histidine, 50 mM to 150 mM sodium chloride, and 50 mM to 150 mM sucrose, wherein the formulation has a pH of 6 to 7. 
     
     
         26 . The formulation of  claim 1 , comprising 25 mg/mL of the antibody molecule, 25 mM histidine, 75 mM sodium chloride, and 100 mM sucrose, wherein the formulation has a pH of 6.5. 
     
     
         27 . The formulation of  claim 1 , comprising 10 mg/mL to 50 mg/mL of the antibody molecule, 10 mM to 50 mM histidine, 50 mM to 150 mM sodium chloride, 50 mM to 150 mM sucrose, 0.01% to 0.05% polysorbate 80, wherein the formulation has a pH of 6 to 7. 
     
     
         28 . The formulation of  claim 1 , comprising 25 mg/mL of the antibody molecule, 25 mM histidine, 75 mM sodium chloride, 100 mM sucrose, 0.02% polysorbate 80, wherein the formulation has a pH of 6.5. 
     
     
         29 . The formulation of  claim 1 , comprising 10 mg/mL to 50 mg/mL of the antibody molecule, 10 mM to 50 mM histidine, 50 mM to 150 mM sodium chloride, and 50 mM to 150 mM arginine, wherein the formulation has a pH of 6 to 7. 
     
     
         30 . The formulation of  claim 1 , comprising 25 mg/mL of the antibody molecule, 25 mM histidine, 75 mM sodium chloride, and 75 mM arginine, wherein the formulation has a pH of 6.5. 
     
     
         31 . The formulation of  claim 1 , comprising 10 mg/mL to 50 mg/mL of the antibody molecule, 10 mM to 50 mM histidine, 50 mM to 150 mM sodium chloride, 50 mM to 150 mM arginine, 0.01% to 0.05% polysorbate 80, wherein the formulation has a pH of 6 to 7. 
     
     
         32 . The formulation of  claim 1 , comprising 25 mg/mL of the antibody molecule, 25 mM histidine, 75 mM sodium chloride, 75 mM arginine, 0.02% polysorbate 80, wherein the formulation has a pH of 6.5. 
     
     
         33 . The formulation of  claim 1 , comprising 10 mg/mL to 50 mg/mL of the antibody molecule, 10 mM to 50 mM sodium citrate, 50 mM to 150 mM sodium chloride, and 50 mM to 150 mM sucrose, wherein the formulation has a pH of 6 to 7. 
     
     
         34 . The formulation of  claim 1 , comprising 25 mg/mL of the antibody molecule, 25 mM sodium citrate, 75 mM sodium chloride, and 75 mM sucrose, wherein the formulation has a pH of 6.5. 
     
     
         35 . The formulation of  claim 1 , which is a liquid formulation. 
     
     
         36 . A container comprising the formulation of  claim 1 . 
     
     
         37 . A device comprising the formulation of  claim 1 . 
     
     
         38 . A kit comprising the formulation of  claim 1 , and instructions for administration of the formulation to a subject. 
     
     
         39 . A method of treating or preventing dengue, the method comprising administering to a subject having dengue, or at risk of having dengue, an effective amount of the formulation of  claim 1 , thereby treating or preventing dengue. 
     
     
         40 . A method of making a formulation comprising an anti-dengue antibody molecule, the method comprising combining the antibody molecule with (a) histidine or sodium citrate, (b) sodium chloride, and (c) arginine or sucrose,
 wherein the antibody molecule comprises:   (a) a heavy chain (HC) immunoglobulin variable region segment comprising:   an HC CDR1 comprising the sequence DVYMS (SEQ ID NO: 3),   an HC CDR2 comprising the sequence RIDPENGDTKYDPKLQG (SEQ ID NO: 4), and   an HC CDR3 comprising the sequence GWEGFAY (SEQ ID NO: 5); and   (b) a light chain (LC) immunoglobulin variable region segment comprising:   an LC CDR1 comprising the sequence RASENVDKYGNSFMH (SEQ ID NO: 6),   an LC CDR2 comprising the sequence RASELQW (SEQ ID NO: 7), and   an LC CDR3 comprising the sequence QRSNEVPWT (SEQ ID NO: 8),   wherein the formulation comprises 10 mg/mL to 50 mg/mL of the antibody molecule, 10 mM to 50 mM histidine or sodium citrate, 50 mM to 150 mM sodium chloride, and 50 mM to 150 mM arginine or sucrose, and   wherein the formulation has a pH of 6 to 7.