Methods of Treating a Tauopathy

Abstract

The present disclosure provides methods of treating a tauopathy, involving administering an anti-Tau antibody. The present disclosure also provides anti-Tau antibodies, and formulations comprising same, for use in the methods.

1 .- 93 . (canceled) 
     
     
         94 . A pharmaceutical composition comprising:
 a) a pharmaceutically acceptable excipient suitable for administration to a human; and   b) a humanized antibody that specifically binds an epitope within an N-terminal portion of a human Tau polypeptide, wherein the humanized antibody competes for binding with an antibody that comprises:
 (i) a V L  CDR1 comprising an amino acid sequence of SEQ ID NO:1; 
 (ii) a V L  CDR2 comprising an amino acid sequence of SEQ ID NO:2; 
 (iii) a V L  CDR3 comprising an amino acid sequence of SEQ ID NO:3; 
 (iv) a V H  CDR1 comprising an amino acid sequence of SEQ ID NO:4; 
 (v) a V H  CDR2 comprising an amino acid sequence of SEQ ID NO:5; and 
 (vi) a V H  CDR3 comprising an amino acid sequence of SEQ ID NO:6 
   or
 (i) a V L  CDR1 comprising an amino acid sequence of SEQ ID NO:7; 
 (ii) a V L  CDR2 comprising an amino acid sequence of SEQ ID NO:8; 
 (iii) a V L  CDR3 comprising an amino acid sequence of SEQ ID NO:9; 
 (iv) a V H  CDR1 comprising an amino acid sequence of SEQ ID NO:10; 
 (v) a V H  CDR2 comprising an amino acid sequence of SEQ ID NO:11; and 
 (vi) a V H  CDR3 comprising an amino acid sequence of SEQ ID NO:12. 
   
     
     
         95 . The pharmaceutical composition of  claim 94 , wherein the humanized antibody comprises a humanized light chain framework region. 
     
     
         96 . The pharmaceutical composition of  claim 94 , wherein the humanized antibody comprises a humanized heavy chain framework region. 
     
     
         97 . The pharmaceutical composition of  claim 94 , wherein the humanized antibody comprises a humanized light chain framework region and a humanized heavy chain framework region. 
     
     
         98 . The pharmaceutical composition of  claim 94 , wherein the humanized antibody is a Fv, scFv, Fab, F(ab′)2, or Fab′. 
     
     
         99 . The pharmaceutical compositions of  claim 94 , wherein the heavy chain region of the humanized antibody is of the isotype IgG1, IgG2, IgG3, or IgG4. 
     
     
         100 . The pharmaceutical composition of  claim 94 , wherein the humanized antibody comprises:
 (i) a V L  CDR1 comprising an amino acid sequence of SEQ ID NO:1;   (ii) a V L  CDR2 comprising an amino acid sequence of SEQ ID NO:2;   (iii) a V L  CDR3 comprising an amino acid sequence of SEQ ID NO:3;   (iv) a V H  CDR1 comprising an amino acid sequence of SEQ ID NO:4;   (v) a V H  CDR2 comprising an amino acid sequence of SEQ ID NO:5; and   (vi) a V H  CDR3 comprising an amino acid sequence of SEQ ID NO:6.   
     
     
         101 . The pharmaceutical composition of  claim 100 , wherein the humanized antibody comprises a humanized light chain framework region. 
     
     
         102 . The pharmaceutical composition of  claim 101 , wherein the humanized light chain framework region comprises an amino acid substitution depicted in Table 3. 
     
     
         103 . The pharmaceutical composition of  claim 100 , wherein the humanized antibody comprises a humanized heavy chain framework region. 
     
     
         104 . The pharmaceutical composition of  claim 103 , wherein the humanized heavy chain framework region comprises an amino acid substitution depicted in Table 2. 
     
     
         105 . The pharmaceutical composition of  claim 100 , wherein the humanized antibody comprises a humanized light chain framework region and a humanized heavy chain framework region. 
     
     
         106 . The pharmaceutical composition of  claim 100 , wherein the humanized antibody comprises a heavy chain region of the isotype IgG1, IgG2, IgG3, or IgG4. 
     
     
         107 . The pharmaceutical composition of  claim 94 , wherein the humanized antibody comprises:
 (i) a V L  CDR1 comprising an amino acid sequence of SEQ ID NO:7;   (ii) a V L  CDR2 comprising an amino acid sequence of SEQ ID NO:8;   (iii) a V L  CDR3 comprising an amino acid sequence of SEQ ID NO:9;   (iv) a V H  CDR1 comprising an amino acid sequence of SEQ ID NO:10;   (v) a V H  CDR2 comprising an amino acid sequence of SEQ ID NO:11; and   (vi) a V H  CDR3 comprising an amino acid sequence of SEQ ID NO:12.   
     
     
         108 . The pharmaceutical composition of  claim 107 , wherein the humanized antibody comprises a humanized light chain framework region. 
     
     
         109 . The pharmaceutical composition of  claim 108 , wherein the humanized light chain framework region comprises an amino acid substitution depicted in Table 3. 
     
     
         110 . The pharmaceutical composition of  claim 107 , wherein the antibody comprises a humanized heavy chain framework region. 
     
     
         111 . The pharmaceutical composition of  claim 110 , wherein the humanized heavy chain framework region comprises an amino acid substitution depicted in Table 2. 
     
     
         112 . The pharmaceutical composition of  claim 107 , wherein the antibody comprises a humanized light chain framework region and a humanized heavy chain framework region. 
     
     
         113 . The pharmaceutical composition of  claim 107 , wherein the humanized antibody comprises a heavy chain region of the isotype IgG1, IgG2, IgG3, or IgG4. 
     
     
         114 . The pharmaceutical composition of  claim 94 , wherein the antibody comprises:
 a) a VH variant 1 comprising the amino acid sequence depicted in  FIG. 9  (SEQ ID NO:36) and a Vk variant 1 comprising the amino acid sequence depicted in  FIG. 13  (SEQ ID NO:40);   b) a VH variant 1 comprising the amino acid sequence depicted in  FIG. 9  (SEQ ID NO:36); and a Vk variant 2 comprising the amino acid sequence depicted in  FIG. 14  (SEQ ID NO:41);   c) a VH variant 1 comprising the amino acid sequence depicted in  FIG. 9  (SEQ ID NO:36); and a Vk variant 3 comprising the amino acid sequence depicted in  FIG. 15  (SEQ ID NO:42);   d) a VH variant 1 comprising the amino acid sequence depicted in  FIG. 9  (SEQ ID NO:36); and a Vk variant 4 comprising the amino acid sequence depicted in  FIG. 16  (SEQ ID NO:43);   e) a VH variant 2 comprising the amino acid sequence depicted in  FIG. 10  (SEQ ID NO:37); and a Vk variant 1 comprising the amino acid sequence depicted in  FIG. 13  (SEQ ID NO:40);   f) a VH variant 2 comprising the amino acid sequence depicted in  FIG. 10  (SEQ ID NO:37); and a Vk variant 2 comprising the amino acid sequence depicted in  FIG. 14  (SEQ ID NO:41);   g) a VH variant 2 comprising the amino acid sequence depicted in  FIG. 10  (SEQ ID NO:37); and a Vk variant 3 comprising the amino acid sequence depicted in  FIG. 15  (SEQ ID NO:42);   h) a VH variant 2 comprising the amino acid sequence depicted in  FIG. 10  (SEQ ID NO:37); and a Vk variant 4 comprising the amino acid sequence depicted in  FIG. 16  (SEQ ID NO:43);   i) a VH variant 3 comprising the amino acid sequence depicted in  FIG. 11  (SEQ ID NO:38); and a Vk variant 1 comprising the amino acid sequence depicted in  FIG. 13  (SEQ ID NO:40);   j) a VH variant 3 comprising the amino acid sequence depicted in  FIG. 11  (SEQ ID NO:38); and a Vk variant 2 comprising the amino acid sequence depicted in  FIG. 14  (SEQ ID NO:41);   k) a VH variant 3 comprising the amino acid sequence depicted in  FIG. 11  (SEQ ID NO:38); and a Vk variant 3 comprising the amino acid sequence depicted in  FIG. 15  (SEQ ID NO:42);   l) a VH variant 3 comprising the amino acid sequence depicted in  FIG. 11  (SEQ ID NO:38); and a Vk variant 4 comprising the amino acid sequence depicted in  FIG. 16  (SEQ ID NO:43);   m) a VH variant 4 comprising the amino acid sequence depicted in  FIG. 12  (SEQ ID NO:39); and a Vk variant 1 comprising the amino acid sequence depicted in  FIG. 13  (SEQ ID NO:40);   n) a VH variant 4 comprising the amino acid sequence depicted in  FIG. 12  (SEQ ID NO:39); and a Vk variant 2 comprising the amino acid sequence depicted in  FIG. 14  (SEQ ID NO:41);   o) a VH variant 4 comprising the amino acid sequence depicted in  FIG. 12  (SEQ ID NO:39); and a Vk variant 3 comprising the amino acid sequence depicted in  FIG. 15  (SEQ ID NO:42); or   p) a VH variant 4 comprising the amino acid sequence depicted in  FIG. 12  (SEQ ID NO:39); and a Vk variant 4 comprising the amino acid sequence depicted in  FIG. 16  (SEQ ID NO:43).   
     
     
         115 . The pharmaceutical composition of  claim 114 , wherein the humanized antibody comprises a heavy chain region of the isotype IgG1, IgG2, IgG3, or IgG4. 
     
     
         116 . The pharmaceutical composition of  claim 94 , wherein the humanized antibody comprises:
 a) a light chain region comprising:
 (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:1; 
 (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:2; 
 (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:3; and 
 (iv) a humanized light chain framework region; and 
   b) a heavy chain region comprising:
 (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:4; 
 (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:5; 
 (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:6; and 
 (iv) a humanized heavy chain framework region. 
   
     
     
         117 . The pharmaceutical composition of  claim 116 , wherein the heavy chain region is of the isotype IgG1, IgG2, IgG3, or IgG4. 
     
     
         118 . The pharmaceutical composition of  claim 94 , wherein the humanized antibody comprises:
 a) a light chain region comprising:
 (i) a VL CDR1 comprising an amino acid sequence of SEQ ID NO:7; 
 (ii) a VL CDR2 comprising an amino acid sequence of SEQ ID NO:8; 
 (iii) a VL CDR3 comprising an amino acid sequence of SEQ ID NO:9; and 
 (iv) a humanized light chain framework region; and 
   b) a heavy chain region comprising:
 (i) a VH CDR1 comprising an amino acid sequence of SEQ ID NO:10; 
 (ii) a VH CDR2 comprising an amino acid sequence of SEQ ID NO:11; 
 (iii) a VH CDR3 comprising an amino acid sequence of SEQ ID NO:12; and 
 (iv) a humanized heavy chain framework region. 
   
     
     
         119 . The pharmaceutical composition of  claim 118 , wherein the heavy chain region is of the isotype IgG1, IgG2, IgG3, or IgG4.