Antibody Formulations and Methods

Abstract

Antibody formulations and methods useful for prophylaxis or treatment of amyloidosis, including AA amyloidosis and AL amyloidosis.

1 . A pharmaceutical formulation comprising:
 (a) a chimeric or humanized version of antibody 2A4 (ATCC Accession Number PTA-9662) or of antibody 7D8 (ATCC Accession Number PTA-9468), or fragment thereof, that specifically competes for binding to antigen with 2A4 or 7D8, wherein the antibody is present at a concentration within the range from about 1 mg/mL to about 100 mg/mL;   (b) histidine buffer present at a concentration within the range from about 20 mM to about 30 mM;   (c) trehalose present at a concentration within the range from about 210 mM to about 250 mM; and   (d) polysorbate 20 present at a concentration within the range from about 0.005% to about 0.05% by weight;   wherein the formulation is characterized by a pH within the range from about 6 to about 7.   
     
     
         2 .- 5 . (canceled) 
     
     
         6 . The formulation of  claim 1 , wherein the antibody comprises a light chain comprising an amino acid sequence set forth as SEQ ID NO: 13 and a heavy chain comprising an amino acid sequence set forth as any one of SEQ ID NO: 14-16. 
     
     
         7 . The formulation of  claim 6 , wherein the antibody comprises a light chain comprising an amino acid sequence set forth as SEQ ID NO: 13 and a heavy chain comprising an amino acid sequence set forth as SEQ ID NO: 15. 
     
     
         8 . The formulation of  claim 1 , wherein the antibody comprises a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7, and 8, and a heavy chain variable region comprising three complementarity regions set forth as SEQ ID NOs: 9, 10, and 11. 
     
     
         9 . The formulation of  claim 1 , wherein the antibody is a humanized or chimeric version of antibody 7D8 produced by ATCC Accession Number PTA-9468. 
     
     
         10 . The formulation of  claim 1 , wherein the antibody comprises a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 12, 7, and 8, and a heavy chain variable region comprising three complementarity regions set forth as SEQ ID NOs: 9, 10, and 11. 
     
     
         11 .- 12 . (canceled) 
     
     
         13 . The formulation of  claim 1 , wherein the antibody is present at a concentration within the range from about 25-75 mg/mL. 
     
     
         14 . The formulation of  claim 13 , wherein the antibody is present at a concentration of about 50 mg/mL. 
     
     
         15 .- 26 . (canceled) 
     
     
         27 . A lyophilized formulation of an antibody, comprising
 (a) a humanized version of antibody 2A4 (ATCC Accession Number PTA-9662) or antibody 7D8 (ATCC Accession Number PTA-9468) or antigen binding fragment thereof,   (b) histidine;   (c) trehalose; and   (d) polysorbate 20.   
     
     
         28 . (canceled) 
     
     
         29 . The lyophilized formulation of  claim 27 , wherein the formulation has a pH of about 6.5 when reconstituted. 
     
     
         30 . The lyophilized formulation of  claim 27 , comprising about 100 mg to about 1000 mg of the antibody. 
     
     
         31 . The lyophilized formulation of  claim 27 , wherein the polysorbate 20 is present at a concentration within the range from about 0.005% to about 0.05% by weight. 
     
     
         32 . The lyophilized formulation of  claim 27 , that enables reconstitution to yield an aqueous solution comprising:
 (a) an antibody comprising a light chain comprising an amino acid sequence set forth as SEQ ID NO: 13 and a heavy chain comprising an amino acid sequence set forth as any one of SEQ ID NOs: 14-16, and which is present at a concentration of about 10 mg/mL;   (b) a histidine buffer present at a concentration of about 25 mM;   (c) trehalose present at a concentration of about 230 mM;   (d) polysorbate 20 present at a concentration of about 0.2 g/L; and   (e) a pH of about 6.5.   
     
     
         33 .- 80 . (canceled) 
     
     
         81 . A method of therapeutically or prophylactically treating a human patient having or at risk for having light chain (AL) amyloidosis characterized by the presence of amyloid fibrils, deposits or prefibrillar aggregates, comprising administering to the patient an effective dosage of a pharmaceutical formulation comprising:
 (a) an antibody comprising a light chain comprising an amino acid sequence set forth as SEQ ID NO: 13 and a heavy chain comprising an amino acid sequence set forth as any one of SEQ ID NOs: 14-16, and which is present at a concentration of about 10 mg/mL;   (b) a histidine buffer present at a concentration of about 25 mM;   (c) trehalose present at a concentration of about 230 mM;   (d) polysorbate 20 present at a concentration of about 0.2 g/L; and   (e) a pH of about 6.5.   
     
     
         82 . The method of  claim 81 , wherein the dosage is from about 0.5 mg/kg to about 30 mg/kg of the antibody administered intravenously or subcutaneously at a frequency of from about weekly to about quarterly. 
     
     
         83 . The method of  claim 82 , wherein the frequency of administration is once every 28 days. 
     
     
         84 . The method of  claim 82 , wherein the dosage is about 0.5 mg/kg to about 8 mg/kg. 
     
     
         85 . The method of  claim 82 , wherein the dosage is about 8 mg/kg to about 30 mg/kg. 
     
     
         86 . (canceled)