Combination therapy

Abstract

A method of treating a cognitive or neurodegenerative disease, comprising administering to a patient in need of such treatment an effective amount of an anti-N3pGlu Abeta antibody, an anti-Abeta antibody, or an antibody fragment that binds Amyloid beta and is covalently attached to a polyethylene glycol molecule, in combination with an effective amount of an anti-Tau antibody.

We claim: 
     
         1 . A method of treating a patient having a disease characterized by formation of amyloid plaques and aberrant tau aggregation, comprising administering to a patient in need of such treatment an effective amount of an anti-Aβ antibody in combination with an effective amount of an anti-Tau antibody,
 wherein the anti-Tau antibody comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the LCVR comprises complementarity determining regions (CDRs) LCDR1, LCDR2, and LCDR3 and the HCVR comprises CDRs HCDR1, HCDR2, and HCDR3, wherein the amino acid sequence of LCDR1 is given by SEQ ID NO. 69, the amino acid sequence of LCDR2 is given by SEQ ID NO. 70, the amino acid sequence of LCDR3 is given by SEQ ID NO. 71, the amino acid sequence of HCDR1 is given by SEQ ID NO. 72, the amino acid sequence of HCDR2 is given by SEQ ID NO. 73, and the amino acid sequence of HCDR3 is given by SEQ ID NO. 75. 
 
     
     
         2 . The method according to  claim 1  wherein the anti-Tau antibody comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the amino acid sequence of the LCVR is given by SEQ ID NO. 75 and the amino acid sequence of the HCVR is given by SEQ ID NO. 76. 
     
     
         3 . The method according to  claim 2 , wherein the anti-Tau antibody comprises a light chain (LC) and a heavy chain (HC), wherein the amino acid sequence of the LC is given by SEQ ID NO. 67 and the amino acid sequence of the HC is given by SEQ ID NO. 68. 
     
     
         4 . The method according to  claim 1 , wherein the anti-Aβ antibody comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the LCVR comprises complementarity determining regions (CDRs) LCDR1, LCDR2, and LCDR3 and the HCVR comprises CDRs HCDR1, HCDR2, and HCDR3, wherein the amino acid sequence of LCDR1 is given by SEQ ID NO. 39, the amino acid sequence of LCDR2 is given by SEQ ID NO. 40, the amino acid sequence of LCDR3 is given by SEQ ID NO. 41, the amino acid sequence of HCDR1 is given by SEQ ID NO. 42, the amino acid sequence of HCDR2 is given by SEQ ID NO. 43, and the amino acid sequence of HCDR3 is given by SEQ ID NO. 44. 
     
     
         5 . The method according to  claim 1 , wherein the anti-Aβ antibody comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the amino acid sequence of the LCVR is given by SEQ ID NO. 45, wherein Xaa at position 2 is Vle or Ile; Xaa at position 7 is Ser or Thr; Xaa at position 14 is Thr or Ser; Xaa at position 15 is Leu or Pro; Xaa at position 30 is Ile or Val; Xaa at position 50 is Arg, Gln, or Lys; Xaa at position 88 is Val or Leu; Xaa at position 105 is Gln or Gly; Xaa at position 108 is Lys or Arg; and Xaa at position 109 is Val or Leu; and the amino acid sequence of the HCVR is given by SEQ ID NO. 46, wherein Xaa at position 1 is Glu or Gln; Xaa at position 7 is Ser or Leu; Xaa at position 46 is Glu, Val, Asp, or Ser; Xaa at position 63 is Thr or Ser; Xaa at position 75 is Ala, Ser, Val or Thr; Xaa at position 76 is Lys or Arg; Xaa at position 89 is Glu or Asp; and Xaa at position 107 is Leu or Thr. 
     
     
         6 . The method according to  claim 1 , wherein the anti-Aβ antibody comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the amino acid sequence of the LCVR is given by SEQ ID NO. 47, and the amino acid sequence of the HCVR is given by SEQ ID NO. 48. 
     
     
         7 . The method according to  claim 1 , wherein the anti-Aβ antibody comprises a light chain (LC) and a heavy chain (HC), wherein the amino acid sequence of the LC is given by SEQ ID NO. 49 and the amino acid sequence of the HC is given by SEQ ID NO. 50. 
     
     
         8 . The method according to  claim 7 , wherein the anti-Aβ antibody comprises two light chains (LC) and two heavy chains (HC), wherein the amino acid sequence of each LC is given by SEQ ID NO. 49 and the amino acid sequence of each HC is given by SEQ ID NO. 50. 
     
     
         9 . The method according to  claim 1 , wherein the disease characterized by formation of amyloid plaques and aberrant tau aggregation is Alzheimer's disease. 
     
     
         10 . The method according to  claim 1 , wherein the disease characterized by formation of amyloid plaques and aberrant tau aggregation is selected from a group consisting of clinical or pre-clinical Alzheimer's disease. 
     
     
         11 . The method according to  claim 1 , wherein the disease characterized by formation of amyloid plaques and aberrant tau aggregation is selected from prodromal Alzheimer's disease, mild Alzheimer's disease, moderate Alzheimer's disease or severe Alzheimer's disease. 
     
     
         12 . The method according to  claim 1 , wherein the anti-Aβ antibody and the anti-Tau antibody are administered simultaneously. 
     
     
         13 . The method according to  claim 1 , wherein the anti-Aβ antibody is administered prior to the administration of the anti-Tau antibody. 
     
     
         14 . A pharmaceutical composition, comprising an anti-Aβ antibody, with one or more pharmaceutically acceptable carriers, diluents, or excipients, in combination with a pharmaceutical composition of anti-Tau antibody, with one or more pharmaceutically acceptable carriers, diluents, or excipients,
 wherein the anti-Tau antibody comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the LCVR comprises complementarity determining regions (CDRs) LCDR1, LCDR2, and LCDR3 and the HCVR comprises CDRs HCDR1, HCDR2, and HCDR3, wherein the amino acid sequence of LCDR1 is given by SEQ ID NO. 69, the amino acid sequence of LCDR2 is given by SEQ ID NO. 70, the amino acid sequence of LCDR3 is given by SEQ ID NO. 71, the amino acid sequence of HCDR1 is given by SEQ ID NO. 72, the amino acid sequence of HCDR2 is given by SEQ ID NO. 73, and the amino acid sequence of HCDR3 is given by SEQ ID NO. 75. 
 
     
     
         15 . The pharmaceutical composition according to  claim 14  wherein the anti-Tau antibody comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the amino acid sequence of the LCVR is given by SEQ ID NO. 75 and the amino acid sequence of the HCVR is given by SEQ ID NO. 76. 
     
     
         16 . The pharmaceutical composition according to  claim 14  wherein the anti-Tau antibody comprises a light chain (LC) and a heavy chain (HC), wherein the amino acid sequence of the LC is given by SEQ ID NO. 67 and the amino acid sequence of the HC is given by SEQ ID NO. 68. 
     
     
         17 . The pharmaceutical composition according to  claim 14 , wherein the anti-Aβ antibody comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR),
 wherein the LCVR comprises complementarity determining regions (CDRs) LCDR1, LCDR2, and LCDR3 and the HCVR comprises CDRs HCDR1, HCDR2, and HCDR3, wherein the amino acid sequence of LCDR1 is given by SEQ ID NO. 39, the amino acid sequence of LCDR2 is given by SEQ ID NO. 40, the amino acid sequence of LCDR3 is given by SEQ ID NO. 44, the amino acid sequence of HCDR1 is given by SEQ ID NO. 42, the amino acid sequence of HCDR2 is given by SEQ ID NO. 43, and the amino acid sequence of HCDR3 is given by SEQ ID NO. 44. 
 
     
     
         18 . The pharmaceutical composition according to  claim 14 , wherein the anti-Aβ antibody comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR),
 wherein the amino acid sequence of the LCVR is given by SEQ ID NO. 45, wherein Xaa at position 2 is Vle or Ile; Xaa at position 7 is Ser or Thr; Xaa at position 14 is Thr or Ser; Xaa at position 15 is Leu or Pro; Xaa at position 30 is Ile or Val; Xaa at position 50 is Arg, Gln, or Lys; Xaa at position 88 is Val or Leu; Xaa at position 105 is Gln or Gly; Xaa at position 108 is Lys or Arg; and Xaa at position 109 is Val or Leu; and the amino acid sequence of the HCVR is given by SEQ ID NO. 46, wherein Xaa at position 1 is Glu or Gln; Xaa at position 7 is Ser or Leu; Xaa at position 46 is Glu, Val, Asp, or Ser; Xaa at position 63 is Thr or Ser; Xaa at position 75 is Ala, Ser, Val or Thr; Xaa at position 76 is Lys or Arg; Xaa at position 89 is Glu or Asp; and Xaa at position 107 is Leu or Thr. 
 
     
     
         19 . The pharmaceutical composition according to  claim 14 , wherein the anti-Aβ antibody comprises a light chain variable region (LCVR) and a heavy chain variable region (HCVR), wherein the amino acid sequence of the LCVR is given by SEQ ID NO. 47, and the amino acid sequence of the HCVR is given by SEQ ID NO. 48. 
     
     
         20 . The pharmaceutical composition according to claim  48 , wherein the anti-Aβ antibody comprises a light chain (LC) and a heavy chain (HC), wherein the amino acid sequence of the LC is given by SEQ ID NO. 49 and the amino acid sequence of the HC is given by SEQ ID NO. 50. 
     
     
         21 . The pharmaceutical composition according to claim  48 , wherein the anti-Aβ antibody comprises two light chains (LC) and two heavy chains (HC), wherein the amino acid sequence of each LC is given by SEQ ID NO. 49 and the amino acid sequence of each HC is given by SEQ ID NO. 50.