Pharmaceutical compositions containing anti-beta amyloid antibodies

Abstract

Pharmaceutical compositions containing anti-beta amyloid (Aβ) antibodies or Aβ-binding fragments thereof are provided. These pharmaceutical compositions find use in the treatment of abnormal accumulation or deposition of Aβ in the central nervous system, mild cognitive impairment, and Aβ-associated disorders such as Alzheimer's disease.

1 . A pharmaceutical composition comprising:
 (i) an anti-beta amyloid (Aβ) antibody or Aβ-binding fragment thereof at a concentration of 50 mg/ml to 150 mg/ml;   (ii) arginine hydrochloride (Arg.HCl) at a concentration of 75 mM to 175 mM;   (iii) methionine at a concentration of 5 mM to 15 mM;   (iv) histidine at a concentration of 10 mM to 30 mM; and   (v) polysorbate-80 (PS80) at a concentration (w/v) of 0.03% to 0.08%,   wherein the anti-Aβ antibody or Aβ-binding fragment thereof comprises an immunoglobulin heavy chain variable domain (VH) and an immunoglobulin light chain variable domain (VL), wherein the VH and VL, respectively, comprising:   (a) the VH comprises:
 a VH-CDR1 that consists of the amino acid sequence set forth in SEQ ID NO:1; 
 a VH-CDR2 that consists of the amino acid sequence set forth in SEQ ID NO:2; and 
 a VH-CDR3 that consists of the amino acid sequence set forth in SEQ ID NO:3; and 
   (b) the VL comprises:
 a VL-CDR1 that consists of the amino acid sequence set forth in SEQ ID NO:4; 
 a VL-CDR2 that consists of the amino acid sequence set forth in SEQ ID NO:5; and 
 a VL-CDR3 that consists of the amino acid sequence set forth in SEQ ID NO:6, and 
   wherein the composition has a pH of 5.2 to 6.2.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the composition comprises the anti-Aβ antibody or Aβ-binding fragment thereof at a concentration of 100 mg/ml. 
     
     
         3 .- 5 . (canceled) 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the composition comprises Arg.HCl at a concentration of 150 mM. 
     
     
         7 .- 8 . (canceled) 
     
     
         9 . The pharmaceutical composition of any one of  claim 1 , wherein the composition comprises Polysorbatc 80 (PS80) PS80 at a concentration (w/v) of 0.05% 0.01% to 0.1%. 
     
     
         10 .- 12 . (canceled) 
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein the composition comprises a histidine buffer at a concentration of 20 mM 10 mM to 30 mM. 
     
     
         14 .- 18 . (canceled) 
     
     
         19 . The pharmaceutical composition of  claim 1 , wherein the composition comprises methionine at a concentration of 10 mM. 
     
     
         20 .- 23 . (canceled) 
     
     
         24 . The pharmaceutical composition of  claim 1 , wherein the composition comprises sucrose at a concentration (w/v) of 0.01% to 3%. 
     
     
         25 .- 27 . (canceled) 
     
     
         28 . The pharmaceutical composition of any one of claim[[s]] 1 t-e-27, wherein the composition has a pH of 5.5. 
     
     
         29 .- 30 . (canceled) 
     
     
         31 . The pharmaceutical composition of  claim 1 , comprising:
 the anti-Aβ antibody or the Aβ-binding fragment thereof at a concentration of 100 mg/ml;   Arg.HCl at a concentration of 150 mM;   methionine at a concentration of 10 mM;   histidine at a concentration of 20 mM; and   PS80 at a concentration of 0.05%,   wherein the composition has a pH of 5.5.   
     
     
         32 .- 33 . (canceled) 
     
     
         34 . A method of treating abnormal accumulation or deposition of Aβ in the central nervous system in a human subject in need thereof, the method comprising administering to the human subject the pharmaceutical composition of  claim 1 . 
     
     
         35 . A method of treating mild cognitive impairment in a human subject in need thereof, the method comprising administering to the human subject the pharmaceutical composition of  claim 1 . 
     
     
         36 . A method of treating Alzheimer's disease in a human subject in need thereof, the method comprising administering to the human subject the pharmaceutical composition of  claim 1 . 
     
     
         37 . (canceled) 
     
     
         38 . The method of any one of  claim 1 , wherein the pharmaceutical composition is administered intravenously to the human subject. 
     
     
         39 .- 90 . (canceled) 
     
     
         91 . The pharmaceutical composition of  claim 1 , comprising:
 the anti-Aβ antibody or the Aβ-binding fragment thereof at a concentration of 100 mg/ml;   Arg.HCl at a concentration of 150 mM;   methionine at a concentration of 10 mM;   histidine at a concentration of 10 mM to 30 mM; and   PS80 at a concentration (w/v) of 0.03% to 0.08%;   wherein the composition has a pH of 5.2 to 5.8.   
     
     
         92 . The pharmaceutical composition of  claim 1 , wherein the VH comprises the amino acid sequence set forth in SEQ ID NO:7 and the VL comprises the amino acid sequence set forth in SEQ ID NO:8. 
     
     
         93 . The pharmaceutical composition of  claim 1 , wherein anti-Aβ antibody or Aβ-binding fragment thereof comprises an immunoglobulin heavy chain and an immunoglobulin light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:9 and the light chain comprises the amino acid sequence set forth in SEQ ID NO:10. 
     
     
         94 . The pharmaceutical composition of  claim 1 , wherein anti-Aβ antibody or Aβ-binding fragment thereof is a human IgG1 antibody. 
     
     
         95 . The pharmaceutical composition of  claim 91 , wherein the VH comprises the amino acid sequence set forth in SEQ ID NO:7 and the VL comprises the amino acid sequence set forth in SEQ ID NO:8. 
     
     
         96 . The pharmaceutical composition of  claim 91 , wherein anti-Aβ antibody or Aβ-binding fragment thereof comprises an immunoglobulin heavy chain and an immunoglobulin light chain, wherein the heavy chain comprises the amino acid sequence set forth in SEQ ID NO:9 and the light chain comprises the amino acid sequence set forth in SEQ ID NO:10. 
     
     
         97 . The pharmaceutical composition of  claim 91 , wherein the anti-Aβ antibody or Aβ-binding fragment thereof is a human IgG1 antibody.