Formulations of antibody molecules to influenza virus

Abstract

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

What is claimed is: 
     
         1 . A formulation comprising 20 mg/mL to 60 mg/mL of an anti-HA antibody molecule, 20 mM to 60 mM citrate-sodium phosphate, and 50 mM to 200 mM sodium chloride, wherein the formulation has a pH of 6 to 6.5, and wherein the antibody molecule comprises:
 (a) a heavy chain (HC) immunoglobulin variable region segment comprising:
 an HC CDR1 comprising the sequence S-Y-A-M-H (SEQ ID NO: 68); 
 an HC CDR2 comprising the sequence V-V-S-Y-D-G-N-Y-K-Y-Y-A-D-S-V-Q-G (SEQ ID NO: 69); and 
 an HC CDR3 comprising the sequence D-S-R-L-R-S-L-L-Y-F-E-W-L-S-Q-G-Y-F-N-P (SEQ ID NO: 70); and 
   (b) a light chain (LC) immunoglobulin variable region segment comprising:
 an LC CDR1 comprising the sequence Q-S-I-T-F-D-Y-K-N-Y-L-A (SEQ ID NO: 145); 
 an LC CDR2 comprising the sequence W-G-S-Y-L-E-S (SEQ ID NO: 72); and 
 an LC CDR3 comprising the sequence Q-Q-H-Y-R-T-P-P-S (SEQ ID NO: 73). 
   
     
     
         2 . The formulation of  claim 1 , further comprising 0.01% to 0.05% polysorbate 80, 
     
     
         3 . The formulation of  claim 1 , comprising 25 mg/mL to 50 mg/mL of the antibody molecule. 
     
     
         4 . The formulation of  claim 1 , comprising 25 mg/mL of the antibody molecule. 
     
     
         5 . The formulation of  claim 1 , wherein the antibody molecule comprises a heavy chain immunoglobulin variable region segment comprising SEQ ID NO: 25, or an amino acid sequence that differs by no more than 1, 2, 3, 4, or 5 amino acids therefrom. 
     
     
         6 . The formulation of  claim 1 , wherein the antibody molecule comprises a light chain immunoglobulin variable region segment comprising SEQ ID NO: 52, or an amino acid sequence that differs by no more than 1, 2, 3, 4, or 5 amino acids therefrom. 
     
     
         7 . The formulation of  claim 1 , wherein the antibody molecule comprises:
 (a) a heavy chain immunoglobulin variable region segment comprising SEQ ID NO: 25, or an amino acid sequence that differs by no more than 1, 2, 3, 4, or 5 amino acids therefrom; and   (b) a light chain immunoglobulin variable region segment comprising SEQ ID NO: 52, or an amino acid sequence that differs by no more than 1, 2, 3, 4, or 5 amino acids therefrom.   
     
     
         8 . The formulation of  claim 1 , wherein the antibody molecule comprises a heavy chain immunoglobulin variable region segment comprising SEQ ID NO: 25, a light chain immunoglobulin variable region segment comprising SEQ ID NO: 52, or both. 
     
     
         9 . The formulation of  claim 1 , comprising 30 mM to 50 mM citrate-sodium phosphate. 
     
     
         10 . The formulation of  claim 1 , comprising 40 mM citrate-sodium phosphate. 
     
     
         11 . The formulation of  claim 1 , comprising 75 mM to 150 mM sodium chloride. 
     
     
         12 . The formulation of  claim 1 , comprising 75 mM sodium chloride. 
     
     
         13 . The formulation of  claim 1 , comprising 150 mM sodium chloride. 
     
     
         14 . The formulation of  claim 1 , which has a pH of 6. 
     
     
         15 . The formulation of  claim 1 , which has a pH of 6.5. 
     
     
         16 . The formulation of  claim 1 , further comprising 0.025% polysorbate 80. 
     
     
         17 . The formulation of  claim 1 , further comprising 0.5% to 2% glycine. 
     
     
         18 . The formulation of  claim 1 , further comprising 1% glycine. 
     
     
         19 . The formulation of  claim 1 , comprising 25 mg/mL of the antibody molecule, 40 mM citrate-sodium phosphate, 150 mM sodium chloride, 0.025% polysorbate 80, wherein the formulation has a pH of 6. 
     
     
         20 . The formulation of  claim 1 , comprising 25 mg/mL of the antibody molecule, 40 mM citrate-sodium phosphate, 150 mM sodium chloride, 0.025% polysorbate 80, wherein the formulation has a pH of 6.5. 
     
     
         21 . The formulation of  claim 1 , comprising 25 mg/mL of the antibody molecule, 40 mM citrate-sodium phosphate, 150 mM sodium chloride, 0.025% polysorbate 80, 1% glycine, wherein the formulation has a pH of 6. 
     
     
         22 . The formulation of  claim 1 , comprising 25 mg/mL of the antibody molecule, 40 mM citrate-sodium phosphate, 150 mM sodium chloride, wherein the formulation has a pH of 6. 
     
     
         23 . The formulation of  claim 1 , comprising 25 mg/mL of the antibody molecule, 40 mM citrate-sodium phosphate, 75 mM sodium chloride, 0.025% polysorbate 80, wherein the formulation has a pH of 6.5. 
     
     
         24 . The formulation of  claim 1 , which is a liquid formulation. 
     
     
         25 . A container comprising the formulation of  claim 1 . 
     
     
         26 . The container of  claim 25 , comprising 10 mL to 50 mL of the formulation. 
     
     
         27 . The container of  claim 25 , comprising 20 mL to 40 mL of the formulation. 
     
     
         28 . The container of  claim 25 , which is a vial. 
     
     
         29 . A method of preparing a composition for administration to a subject, the method comprises combining the formulation of  claim 1  with a solution suitable for intravenous administration. 
     
     
         30 . The method of  claim 29 , wherein the solution comprises saline. 
     
     
         31 . The method of  claim 30 , wherein the solution further comprises dextrose. 
     
     
         32 . The method of  claim 29 , wherein 2000 mg to 5000 mg of the antibody molecule is combined with the solution. 
     
     
         33 . The method of  claim 29 , wherein 2300 mg to 4600 mg of the antibody molecule is combined with the solution. 
     
     
         34 . The method of  claim 29 , wherein the formulation is combined with the solution in an intravenous solution bag. 
     
     
         35 . A method of treating or preventing influenza, the method comprising administering to a subject having influenza, or at risk of having influenza, an effective amount of the formulation of  claim 1 , thereby treating or preventing influenza. 
     
     
         36 . The method of  claim 35 , wherein the formulation is administered to the subject intravenously. 
     
     
         37 . A container comprising 200 mL to 300 mL of a solution comprising an anti-HA antibody molecule, wherein the solution is suitable for intravenous administration, wherein the antibody molecule is present at a concentration of 5 mg/mL to 20 mg/mL, and wherein the antibody molecule comprises:
 (a) a heavy chain (HC) immunoglobulin variable region segment comprising:
 an HC CDR1 comprising the sequence S-Y-A-M-H (SEQ ID NO: 68); 
 an HC CDR2 comprising the sequence V-V-S-Y-D-G-N-Y-K-Y-Y-A-D-S-V-Q-G (SEQ ID NO: 69); and 
 an HC CDR3 comprising the sequence D-S-R-L-R-S-L-L-Y-F-E-W-L-S-Q-G-Y-F-N-P (SEQ ID NO: 70); and 
   (b) a light chain (LC) immunoglobulin variable region segment comprising:
 an LC CDR1 comprising the sequence Q-S-I-T-F-D-Y-K-N-Y-L-A (SEQ ID NO: 145); 
 an LC CDR2 comprising the sequence W-G-S-Y-L-E-S (SEQ ID NO: 72); and 
 an LC CDR3 comprising the sequence Q-Q-H-Y-R-T-P-P-S (SEQ ID NO: 73). 
   
     
     
         38 . The container of  claim 37 , comprising 250 mL of a solution comprising the antibody molecule. 
     
     
         39 . The container of  claim 37 , wherein the antibody molecule is present at a concentration of 8 mg/mL to 16 mg/mL. 
     
     
         40 . The container of  claim 37 , wherein the antibody molecule comprises a heavy chain immunoglobulin variable region segment comprising SEQ ID NO: 25, a light chain immunoglobulin variable region segment comprising SEQ ID NO: 52, or both. 
     
     
         41 . The container of  claim 37 , which is an intravenous (IV) solution bag.