Monoclonal antibodies against amyloid beta protein and uses thereof
View Patent ↗The subject invention relates to monoclonal antibodies (e.g., 8F5 and 8C5) that may be used, for example, in the prevention, treatment and diagnosis of Alzheimer's Disease or other neurodegenerative disorders.
1. A monoclonal antibody comprising:
a) a light chain variable region CDR 1 comprising the amino acid sequence of SEQ ID NO:8;
b) a light chain variable region CDR 2 comprising the amino acid sequence of SEQ ID NO:9;
c) a light chain variable region CDR 3 comprising the amino acid sequence of SEQ ID NO:10;
d) a heavy chain variable region CDR 1 comprising the amino acid sequence of SEQ ID NO:5;
e) a heavy chain variable region CDR 2 he comprising the amino acid sequence of SEQ ID NO:6; and
f) a heavy chain variable region CDR 3 comprising the amino acid sequence of SEQ ID NO: 7;
wherein the monoclonal antibody binds amyloid beta globulomer.
2. The monoclonal antibody of claim 1 , wherein the antibody binds with greater specificity to an amyloid beta (Aβ) protein globulomer than to an amyloid beta protein monomer.
3. A monoclonal antibody which specifically binds to forms of amyloid beta, wherein:
the light chain variable region of the monoclonal antibody comprises the amino acid sequence of RSSQSLVYSNGDTYLH (SEQ ID NO: 8); the amino acid sequence of KVSNRFS (SEQ ID NO: 9); and the amino acid sequence of SQSTHVPWT (SEQ ID NO: 10); and
the heavy chain variable region of the monoclonal antibody comprises the amino acid sequence of GFTFSSYGMS (SEQ ID NO: 24); the amino acid sequence of SINSNGGSTYYPDSVKG (SEQ ID NO: 6); and the amino acid sequence of GDY (SEQ ID NO: 25);
wherein the monoclonal antibody binds amyloid beta globulomer.
4. The monoclonal antibody of claim 1 or 3 , wherein said antibody is murine or humanized.
5. A monoclonal antibody comprising a variable heavy chain encoded by SEQ ID NO:1, wherein the monoclonal antibody binds amyloid beta globulomer.
6. A monoclonal antibody comprising a variable light chain encoded by SEQ ID NO:2, wherein the monoclonal antibody binds amyloid beta globulomer.
7. The monoclonal antibody of claim 6 further comprising a variable heavy chain encoded by SEQ ID NO:1, wherein the monoclonal antibody binds amyloid beta globulomer.
8. A monoclonal antibody, wherein the variable heavy chain comprises SEQ ID NO:3, wherein the monoclonal antibody binds amyloid beta globulomer.
9. A monoclonal antibody, wherein the variable light chain comprises SEQ ID NO:4, wherein the monoclonal antibody binds amyloid beta globulomer.
10. The monoclonal antibody of claim 9 further comprising SEQ ID NO:3.
11. A monoclonal antibody comprising the complementarity determining regions of SEQ ID NO:3 and SEQ ID NO:4, wherein said antibody is murine or humanized, wherein the monoclonal antibody binds amyloid beta globulomer.
12. A hybridoma that produces a monoclonal antibody having a variable heavy chain comprising SEQ ID NO:3 and a variable light chain comprising SEQ ID NO:4.
13. A monoclonal antibody produced by the hybridoma of claim 12 .
14. A monoclonal antibody comprising:
a) a light chain variable region CDR 1 comprising the amino acid sequence of SEQ ID NO:8;
b) a light chain variable region CDR 2 comprising the amino acid sequence of SEQ ID NO:9; and
c) a light chain variable region CDR 3 comprising the amino acid sequence of SEQ ID NO:10; and
d) a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:3;
wherein the monoclonal antibody binds amyloid beta globulomer.
15. A monoclonal antibody comprising:
a) a heavy chain variable region CDR 1 comprising the amino acid sequence of SEQ ID NO:5;
b) a heavy chain variable region CDR 2 comprising the amino acid sequence of SEQ ID NO:6;
c) a heavy chain variable region CDR 3 comprising the amino acid sequence of SEQ ID NO:7; and
d) a light chain variable region comprising the amino acid sequence of SEQ ID NO:4;
wherein the monoclonal antibody binds amyloid beta globulomer.
16. A hybridoma having American Type Culture Collection designation number PTA-7238.
17. A monoclonal antibody (8F5) produced by said hybridoma of claim 16 .
18. . A composition comprising the monoclonal antibody of claim 17 or claim 1 .
19. A vaccine comprising the monoclonal antibody of claim 17 or claim 1 and a pharmaceutically acceptable adjuvant.
20. A kit comprising: a) the monoclonal antibody of claim 17 or claim 1 and b) a conjugate comprising an antibody attached to a signal-generating compound, wherein said antibody of said conjugate is different from said monoclonal antibody.