Anti-alpha-synuclein antibodies and methods of use

Abstract

The present invention relates to anti-alpha-synuclein (anti-α-synuclein) antibodies and methods of using the same.

What is claimed is: 
     
         1 . An isolated monoclonal antibody that competes with an anti-α-synuclein antibody for binding to human α-synuclein, wherein the anti-α-synuclein antibody comprises three heavy chain hypervariable regions (HVR-H1, HVR-H2, and HVR-H3) and three light chain hypervariable regions (HVR-L1, HVR-L2, and HVR-L3), wherein:
 (a) HVR-H1 comprises the amino acid sequence of SEQ ID NO:9; 
 (b) HVR-H2 comprises the amino acid sequence of SEQ ID NO:10; 
 (c) HVR-H3 comprises the amino acid sequence of SEQ ID NO:11; 
 (d) HVR-L1 comprises the amino acid sequence of SEQ ID NO:6; 
 (e) HVR-L2 comprises the amino acid sequence of SEQ ID NO:7; and 
 (f) HVR-L3 comprises the amino acid sequence of SEQ ID NO:8. 
 
     
     
         2 . The isolated monoclonal antibody of  claim 1 , wherein the anti-α-synuclein antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:3, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:2. 
     
     
         3 . An isolated monoclonal antibody that binds to the same epitope in human α-synuclein as an anti-α-synuclein antibody comprising three heavy chain hypervariable regions (HVR-H1, HVR-H2, and HVR-H3) and three light chain hypervariable regions (HVR-L1, HVR-L2, and HVR-L3), wherein:
 (a) HVR-H1 comprises the amino acid sequence of SEQ ID NO:9; 
 (b) HVR-H2 comprises the amino acid sequence of SEQ ID NO:10; 
 (c) HVR-H3 comprises the amino acid sequence of SEQ ID NO:11; 
 (d) HVR-L1 comprises the amino acid sequence of SEQ ID NO:6; 
 (e) HVR-L2 comprises the amino acid sequence of SEQ ID NO:7; and 
 (f) HVR-L3 comprises the amino acid sequence of SEQ ID NO:8. 
 
     
     
         4 . The isolated monoclonal antibody of  claim 3 , wherein the anti-α-synuclein antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:2, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:3. 
     
     
         5 . An isolated monoclonal antibody that competes with an anti-α-synuclein antibody for binding to human α-synuclein, wherein the anti-α-synuclein antibody comprises three heavy chain hypervariable regions (HVR-H1, HVR-H2, and HVR-H3) and three light chain hypervariable regions (HVR-L1, HVR-L2, and HVR-L3), wherein:
 (a) HVR-H1 comprises the amino acid sequence of SEQ ID NO:15; 
 (b) HVR-H2 comprises the amino acid sequence of SEQ ID NO:16; 
 (c) HVR-H3 comprises the amino acid sequence of SEQ ID NO:17; 
 (d) HVR-L1 comprises the amino acid sequence of SEQ ID NO:12; 
 (e) HVR-L2 comprises the amino acid sequence of SEQ ID NO:13; and 
 (f) HVR-L3 comprises the amino acid sequence of SEQ ID NO:14. 
 
     
     
         6 . The isolated monoclonal antibody of  claim 5 , wherein the anti-α-synuclein antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:5, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:4. 
     
     
         7 . An isolated monoclonal antibody that binds to the same epitope in human α-synuclein as an anti-α-synuclein antibody comprising three heavy chain hypervariable regions (HVR-H1, HVR-H2, and HVR-H3) and three light chain hypervariable regions (HVR-L1, HVR-L2, and HVR-L3), wherein:
 (a) HVR-H1 comprises the amino acid sequence of SEQ ID NO:15; 
 (b) HVR-H2 comprises the amino acid sequence of SEQ ID NO:16; 
 (c) HVR-H3 comprises the amino acid sequence of SEQ ID NO:17; 
 (d) HVR-L1 comprises the amino acid sequence of SEQ ID NO:12; 
 (e) HVR-L2 comprises the amino acid sequence of SEQ ID NO:13; and 
 (f) HVR-L3 comprises the amino acid sequence of SEQ ID NO:14. 
 
     
     
         8 . The isolated monoclonal antibody of  claim 7 , wherein the anti-α-synuclein antibody comprises a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:5, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:4. 
     
     
         9 . An isolated antibody that binds to human α-synuclein, wherein the antibody binds a region or epitope of human α-synuclein comprising amino acid residues 5-43 of human α-synuclein. 
     
     
         10 . The isolated antibody of  claim 9 , wherein the antibody binds human α-synuclein at amino acid residue number 5, 8, 9, 15-22, 28, and 39-43. 
     
     
         11 . An isolated antibody that binds to human α-synuclein, wherein the antibody binds a region or epitope of human α-synuclein comprising amino acid residues 5-78 of human α-synuclein, wherein the amino acid residues are numbered according to the human α-synuclein amino acid sequence of SEQ ID NO:1. 
     
     
         12 . The isolated antibody of  claim 11 , wherein the antibody binds human α-synuclein at amino acid residue number 5, 8, 9, 15-22, 28, 39-43, and 78. 
     
     
         13 . An isolated antibody that binds to human α-synuclein, wherein the antibody binds a region or epitope of human α-synuclein comprising amino acid residues 37-51 of human α-synuclein, wherein the amino acid residues are numbered according to the human α-synuclein amino acid sequence of SEQ ID NO:1. 
     
     
         14 . An isolated antibody that binds to human α-synuclein, wherein the antibody binds a region or epitope of human α-synuclein comprising amino acid residues 104-118 of human α-synuclein, wherein the amino acid residues are numbered according to the human α-synuclein amino acid sequence of SEQ ID NO:1. 
     
     
         15 . The isolated antibody of  claim 14 , wherein the antibody binds human α-synuclein at amino acid residues 104, 105, 107, 109-111, 113-116, and 118.