Anti-rsv monoclonal antibody formulation

Abstract

The present invention provides a formulation comprising: (i) an anti-RSV monoclonal antibody; and (ii) an ionic excipient; wherein the monoclonal antibody is present at a concentration of about 50 mg/ml or greater and the ionic excipient is present at a concentration of between 50 and 150 mM and the formulation has a pH of about 5.5 to about 7.5.

1 - 36 . (canceled) 
     
     
         37 . A formulation comprising:
 an anti-Respiratory Syncytial Virus (RSV) monoclonal antibody that is present at a concentration of about 50 mg/ml or greater and comprises a light chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 9 and a heavy chain variable region having at least 90% identity to the amino acid sequence of SEQ ID NO: 10;   wherein the formulation further comprises an ionic excipient present at a concentration of about 50 mM to about 150 mM and one or more buffers present at a concentration of about 10 mM to about 50 mM; and   wherein the formulation has a pH of about 5.5 to about 7.5.   
     
     
         38 . The formulation of  claim 37 , wherein the light chain variable region has at least 95% identity to the amino acid sequence of SEQ ID NO: 9 and the heavy chain variable region has at least 95% identity to the amino acid sequence of SEQ ID NO: 10. 
     
     
         39 . The formulation of  claim 37 , wherein
 the light chain variable region comprises CDR sequences:
 CDR-L1 of SEQ ID NO: 3 
 CDR-L2 of SEQ ID NO: 4 
 CDR-L3 of SEQ ID NO: 5; 
   and the heavy chain variable region comprises CDR sequences:
 CDR-H1 of SEQ ID NO: 6 
 CDR-H2 of SEQ ID NO: 7 
 CDR-H3 of SEQ ID NO: 8. 
   
     
     
         40 . The formulation of  claim 37 , wherein the monoclonal antibody is present at a concentration of about 75 mg/ml to about 200 mg/ml. 
     
     
         41 . The formulation of  claim 40 , wherein the monoclonal antibody is present at a concentration of about 100 mg/ml to about 165 mg/ml. 
     
     
         42 . The formulation of  claim 41 , wherein the monoclonal antibody is present at a concentration of about 100 mg/ml. 
     
     
         43 . The formulation of  claim 37 , wherein the ionic excipient comprises arginine or lysine. 
     
     
         44 . The formulation of  claim 37 , wherein the ionic excipient comprises arginine hydrochloride. 
     
     
         45 . The formulation of  claim 44 , wherein the arginine hydrochloride is present at a concentration of about 75 mM to about 100 mM. 
     
     
         46 . The formulation of  claim 45 , wherein the arginine hydrochloride is present at a concentration of about 80 mM. 
     
     
         47 . The formulation of  claim 37 , wherein the one or more buffers comprises histidine, histidine hydrochloride, or a combination thereof. 
     
     
         48 . The formulation of  claim 37 , wherein the one or more buffers comprises L-histidine, L-histidine hydrochloride, or a combination thereof. 
     
     
         49 . The formulation of  claim 48 , wherein the one or more buffers is present at a concentration of about 30 mM. 
     
     
         50 . The formulation of  claim 37 , further comprising sucrose at a concentration of about 100 mM to about 140 mM. 
     
     
         51 . The formulation of  claim 50 , wherein the sucrose is present at a concentration of about 120 mM. 
     
     
         52 . The formulation of  claim 37 , further comprising polysorbate-80 at a concentration of about 0.02% (w/v) to about 0.07% (w/v). 
     
     
         53 . The formulation of  claim 52 , wherein the polysorbate-80 is present at a concentration of about 0.02% (w/v) or about 0.04% (w/v). 
     
     
         54 . The formulation of  claim 37 , wherein the formulation has a pH of about 5.7 to about 6.3. 
     
     
         55 . The formulation of  claim 54 , wherein the formulation has a pH of about 6.0. 
     
     
         56 . The formulation of  claim 37 ,
 wherein the monoclonal antibody is present at a concentration of about 75 mg/ml to about 200 mg/ml; the ionic excipient comprises about 75 mM to about 100 mM arginine hydrochloride; and the one or more buffers comprises about 10 mM to about 50 mM histidine, histidine hydrochloride, or a combination thereof; and   wherein the formulation further comprises about 100 mM to about 140 mM sucrose and about 0.02% (w/v) to about 0.07% (w/v) polysorbate-80;   wherein the formulation has a pH of about 5.5 to about 6.5.   
     
     
         57 . The formulation of  claim 56 , wherein the light chain variable region has at least 95% identity to the amino acid sequence of SEQ ID NO: 9 and the heavy chain variable region has at least 95% identity to the amino acid sequence of SEQ ID NO: 10. 
     
     
         58 . The formulation of  claim 56 , wherein
 the light chain variable region comprises CDR sequences:
 CDR-L1 of SEQ ID NO: 3 
 CDR-L2 of SEQ ID NO: 4 
 CDR-L3 of SEQ ID NO: 5; 
   and the heavy chain variable region comprises CDR sequences:
 CDR-H1 of SEQ ID NO: 6 
 CDR-H2 of SEQ ID NO: 7 
 CDR-H3 of SEQ ID NO: 8. 
   
     
     
         59 . The formulation of  claim 37 , wherein the formulation is liquid. 
     
     
         60 . A method of preventing RSV lower respiratory tract disease in a subject, comprising administering to the subject the formulation of  claim 37 . 
     
     
         61 . The method of  claim 60 , wherein the subject is under two years of age. 
     
     
         62 . A formulation comprising:
 an anti-Respiratory Syncytial Virus (RSV) monoclonal antibody at 100 mg/mL, wherein the antibody comprises a light chain sequence of SEQ ID NO: 1 and a heavy chain sequence of SEQ ID NO: 2;   30 mM L-histidine/L-histidine hydrochloride;   80 mM L-arginine hydrochloride;   120 mM sucrose; and   0.02% (w/v) polysorbate 80,   wherein the pharmaceutical formulation has a pH of 6.0.   
     
     
         63 . A method of preventing RSV lower respiratory tract disease in a subject, comprising administering to the subject the formulation of  claim 62 .