Anti-Abeta antibodies and uses thereof
An isolated antibody, comprising a light-chain CDR1 (L-CDR1) having the sequence of SEQ ID NO: 1, SEQ ID NO: 7, or SEQ ID NO: 14; a light-chain CDR2 (L-CDR2) having the sequence of SEQ ID NO: 2 or SEQ ID NO: 15; a light-chain CDR3 (L-CDR3) having the sequence of SEQ ID NO: 3, SEQ ID NO: 8, SEQ ID NO: 21, or SEQ ID NO: 24; a heavy-chain CDR1 (H-CDR1) having the sequence of SEQ ID NO: 4, SEQ ID NO: 9, SEQ ID NO: 11, SEQ ID NO: 16, or SEQ ID NO: 25; a heavy-chain CDR2 (H-CDR2) having the sequence of SEQ ID NO: 5, SEQ ID NO: 12, SEQ ID NO: 17, SEQ ID NO: 19, SEQ ID NO: 22, or SEQ ID NO: 26; and a heavy-chain CDR3 (H-CDR3) having the sequence of SEQ ID NO: 6, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 18, SEQ ID NO: 20, SEQ ID NO: 23, or SEQ ID NO: 27, wherein the antibody specifically binds to Aβ 1-42 or an N-terminal modified form thereof.
1. An isolated antibody, comprising a light-chain CDR1 (L-CDR1); a light-chain CDR2 (L-CDR2); a light-chain CDR3 (L-CDR3); a heavy-chain CDR1 (H-CDR1); a heavy-chain CDR2 (H-CDR2); and a heavy-chain CDR3 (H-CDR3), wherein the antibody specifically binds to Aβ 1-42 or an N-terminal modified form of Aβ 1-42 , and
wherein:
(i) the H-CDR1 has the sequence of SEQ ID NO: 16, the H-CDR2 has the sequence of SEQ ID NO: 17 or 19, the H-CDR3 has the sequence of SEQ ID NO: 18 or 20, the L-CDR1 has the sequence of SEQ ID NO: 14, the L-CDR2 has the sequence of SEQ ID NO: 15, and the L-CDR3 has the sequence of SEQ ID NO: 3;
(ii) the H-CDR1 has the sequence of SEQ ID NO: 4, the H-CDR2 has the sequence of SEQ ID NO: 5, the H-CDR3 has the sequence of SEQ ID NO: 6, the L-CDR1 has the sequence of SEQ ID NO: 1, the L-CDR2 has the sequence of SEQ ID NO: 2, and the L-CDR3 has the sequence of SEQ ID NO: 3;
(iii) the H-CDR1 has the sequence of SEQ ID NO: 9, the H-CDR2 has the sequence of SEQ ID NO: 5, the H-CDR3 has the sequence of SEQ ID NO: 10, the L-CDR1 has the sequence of SEQ ID NO: 7, the L-CDR2 has the sequence of SEQ ID NO: 2, and the L-CDR3 has the sequence of SEQ ID NO: 8;
(iv) the H-CDR1 has the sequence of SEQ ID NO: 11, the H-CDR2 has the sequence of SEQ ID NO: 12, the H-CDR3 has the sequence of SEQ ID NO: 13, the L-CDR1 has the sequence of SEQ ID NO: 7, the L-CDR2 has the sequence of SEQ ID NO: 2, and the L-CDR3 has the sequence of SEQ ID NO: 3;
(v) the H-CDR1 has the sequence of SEQ ID NO: 9, the H-CDR2 has the sequence of SEQ ID NO: 22, the H-CDR3 has the sequence of SEQ ID NO: 23, the L-CDR1 has the sequence of SEQ ID NO: 7, the L-CDR2 has the sequence of SEQ ID NO: 2, and the L-CDR3 has the sequence of SEQ ID NO: 21; or
(vi) the H-CDR1 has the sequence of SEQ ID NO: 25, the H-CDR2 has the sequence of SEQ ID NO: 26, the H-CDR3 has the sequence of SEQ ID NO: 27, the L-CDR1 has the sequence of SEQ ID NO: 7, the L-CDR2 has the sequence of SEQ ID NO: 2, and the L-CDR3 has the sequence of SEQ ID NO: 24.
2. The isolated antibody of claim 1 , wherein the H-CDR1 has the sequence of SEQ ID NO: 16, the H-CDR2 has the sequence of SEQ ID NO: 19, the H-CDR3 has the sequence of SEQ ID NO: 20, the L-CDR1 has the sequence of SEQ ID NO: 14, the L-CDR2 has the sequence of SEQ ID NO: 15, and the L-CDR3 has the sequence of SEQ ID NO: 3.
3. The isolated antibody of claim 2 , wherein the N-terminal modified Aβ 1-42 is pyro-glutamate Aβ (pE-Aβ 3-42 ).
4. The isolated antibody of claim 1 , wherein the N-terminal modified Aβ 1-42 is pyro-glutamate Aβ (pE-Aβ 3-42 ).
5. The isolated antibody of claim 1 , wherein the H-CDR1 has the sequence of SEQ ID NO: 4, the H-CDR2 has the sequence of SEQ ID NO: 5, the H-CDR3 has the sequence of SEQ ID NO: 6, the L-CDR1 has the sequence of SEQ ID NO: 1, the L-CDR2 has the sequence of SEQ ID NO: 2, and the L-CDR3 has the sequence of SEQ ID NO: 3.
6. The isolated antibody of claim 1 , wherein the H-CDR1 has the sequence of SEQ ID NO: 9, the H-CDR2 has the sequence of SEQ ID NO: 5, the H-CDR3 has the sequence of SEQ ID NO: 10, the L-CDR1 has the sequence of SEQ ID NO: 7, the L-CDR2 has the sequence of SEQ ID NO: 2, and the L-CDR3 has the sequence of SEQ ID NO: 8.
7. The isolated antibody of claim 1 , wherein the H-CDR1 has the sequence of SEQ ID NO: 11, the H-CDR2 has the sequence of SEQ ID NO: 12, the H-CDR3 has the sequence of SEQ ID NO: 13, the L-CDR1 has the sequence of SEQ ID NO: 7, the L-CDR2 has the sequence of SEQ ID NO: 2, and the L-CDR3 has the sequence of SEQ ID NO: 3.
8. The isolated antibody of claim 1 , wherein the H-CDR1 has the sequence of SEQ ID NO: 16, the H-CDR2 has the sequence of SEQ ID NO: 17, the H-CDR3 has the sequence of SEQ ID NO: 18, the L-CDR1 has the sequence of SEQ ID NO: 14, the L-CDR2 has the sequence of SEQ ID NO: 15, and the L-CDR3 has the sequence of SEQ ID NO: 3.
9. The isolated antibody of claim 1 , wherein the H-CDR1 has the sequence of SEQ ID NO: 9, the H-CDR2 has the sequence of SEQ ID NO: 22, the H-CDR3 has the sequence of SEQ ID NO: 23, the L-CDR1 has the sequence of SEQ ID NO: 7, the L-CDR2 has the sequence of SEQ ID NO: 2, and the L-CDR3 has the sequence of SEQ ID NO: 21.
10. The isolated antibody of claim 1 , wherein the H-CDR1 has the sequence of SEQ ID NO: 25, the H-CDR2 has the sequence of SEQ ID NO: 26, the H-CDR3 has the sequence of SEQ ID NO: 27, the L-CDR1 has the sequence of SEQ ID NO: 7, the L-CDR2 has the sequence of SEQ ID NO: 2, and the L-CDR3 has the sequence of SEQ ID NO: 24.
11. The antibody of claim 1 , wherein the antibody is an antibody containing an Fc region, an Fab fragment, an Fab′ fragment, an F(ab′)2 fragment, a single-chain antibody, an scFV multimer, a monoclonal antibody, a monovalent antibody, a multispecific antibody, a humanized antibody, or a chimeric antibody.
12. A pharmaceutical composition, comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
13. The pharmaceutical composition of claim 12 , wherein the antibody comprises H-CDR1 having the sequence of SEQ ID NO: 16, H-CDR2 having the sequence of SEQ ID NO: 19, H-CDR3 having the sequence of SEQ ID NO: 20, L-CDR1 having the sequence of SEQ ID NO: 14, L-CDR2 having the sequence of SEQ ID NO: 15, and L-CDR3 having the sequence of SEQ ID NO: 3.
14. A method for treating Alzheimer's disease in a subject, the method comprising identifying a subject suffering from Alzheimer's disease and administering to the subject an effective amount of the antibody of claim 1 .
15. The method of claim 14 , wherein the antibody comprises H-CDR1 having the sequence of SEQ ID NO: 16, H-CDR2 having the sequence of SEQ ID NO: 19, H-CDR3 having the sequence of SEQ ID NO: 20, L-CDR1 having the sequence of SEQ ID NO: 14, L-CDR2 having the sequence of SEQ ID NO: 15, and L-CDR3 having the sequence of SEQ ID NO: 3.
16. The method of claim 15 , wherein the identifying step includes administering to the subject the antibody of claim 1 , and measuring a peripheral blood level of AP protein in the subject, wherein the peripheral blood level positively correlates with the level of cerebral AP protein.
17. A method for detecting cerebral AP protein in a subject, the method comprising administering to the subject the antibody of claim 1 , and measuring a peripheral blood level of AP protein in the subject, wherein the peripheral blood level positively correlates with the level of cerebral AP protein.
18. The method of claim 17 , wherein the antibody comprises H-CDR1 having the sequence of SEQ ID NO: 16, H-CDR2 having the sequence of SEQ ID NO: 19, H-CDR3 having the sequence of SEQ ID NO: 20, L-CDR1 having the sequence of SEQ ID NO: 14, L-CDR2 having the sequence of SEQ ID NO: 15, and L-CDR3 having the sequence of SEQ ID NO: 3.
19. A method for labeling an AP plaque in a subject, the method comprising labeling the antibody of claim 1 with a detectable label, administering the labeled antibody to a subject, and detecting a location of the label in the subject.
20. The method of claim 19 , wherein the label is radioactive and the detection is carried out by positron emission tomography.