Anti-alpha-synuclein antibodies

1. An antibody that binds to alpha synuclein or an antigen binding fragment of the antibody, wherein the antibody or the antigen binding fragment of the antibody comprises:

a) a light chain variable region comprising:

i) a CDR-L1 comprising SEQ ID NO: 1;

ii) a CDR-L2 comprising SEQ ID NO: 2; and

iii) a CDR-L3 comprising SEQ ID NO: 3; and

b) a heavy chain variable region comprising:

i) a CDR-H1 comprising SEQ ID NO: 4;

ii) a CDR-H2 comprising SEQ ID NO: 5; and

iii) a CDR-H3 comprising SEQ ID NO: 6.

2. The antibody or antigen-binding fragment of claim 1 , wherein the antibody comprises a light chain variable region comprising SEQ ID NO: 15 and a heavy chain variable region comprising SEQ ID NO: 31.

3. The antibody or antigen-binding fragment of claim 1 , wherein the antibody comprises a light chain comprising SEQ ID NO: 17 and a heavy chain comprising SEQ ID SEQ ID NO: 33.

4. The antibody or the antigen-binding fragment of claim 1 , wherein the antibody binds an alpha synuclein epitope comprising, with reference to SEQ ID NO: 10, residues E123, Y125, E126, M127, P128, S129, E130 and E131, wherein the epitope optionally comprises A124 and G132.

5. The antibody or antigen-binding fragment according to claim 1 , wherein the antibody or antigen-binding fragment prevents aggregation of alpha synuclein induced by alpha synuclein fibrils.

6. The antibody or the antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment is capable of binding alpha synuclein as a monomer and in fibrils.

7. The antibody or the antigen-binding fragment of claim 1 , wherein the antibody or the antigen-binding fragment has a higher binding affinity for alpha synuclein in fibrils compared to monomeric alpha synuclein characterized by a constant of dissociation (KD) at least 10-fold higher for monomeric alpha synuclein than for alpha synuclein in fibrils.

8. The antibody or the antigen-binding fragment of claim 1 , wherein the antibody or the antigen-binding fragment has a (KD) for alpha synuclein in fibrils of 300 pM or less.

9. The antibody or the antigen-binding fragment of claim 1 , wherein the antibody or the antigen-binding fragment does not bind beta synuclein and/or gamma synuclein.

10. The antibody or the antigen-binding fragment of claim 1 , wherein the antibody is a chimeric or humanized antibody.

11. The antibody or antigen-binding fragment of claim 1 , wherein the antibody is a full length antibody.

12. The antibody or antigen-binding fragment of claim 11 , wherein the full-length antibody is an IgG1, IgG4 or IgG4P.

13. The antibody or antigen-binding fragment of claim 1 , wherein the antigen-binding fragment is a Fab, a Fab′, a F(ab′)2, or a scFv.

14. An isolated polynucleotide encoding the antibody or the antigen-binding fragment of claim 1 .

15. The isolated polynucleotide according to claim 14 , wherein the polynucleotide encodes:

a. a light chain variable region, wherein the polynucleotide:

i) comprises a sequence that is at least 90% identical to SEQ ID NO: 16; or

ii) comprises SEQ ID NO: 16; or

b. a heavy chain variable region, wherein the polynucleotide:

i) comprises a sequence that is at least 90% identical to SEQ ID NO: 32; or

ii) comprises SEQ ID NO: 32.

16. A host cell comprising the polynucleotide of claim 14 .

17. A cloning or expression vector comprising the polynucleotide of claim 14 .

18. A host cell comprising the expression vector of claim 17 .

19. A process for producing the antibody or antigen-binding fragment of claim 1 , comprising culturing a host cell comprising a polynucleotide encoding the antibody or antigen-binding fragment under suitable conditions for producing the antibody or antigen-binding fragment and isolating the antibody or antigen-binding fragment.

20. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 1 and one or more pharmaceutically acceptable carriers, excipients or diluents.

21. An antibody that binds to alpha-synuclein or an antigen-binding fragment of the antibody, wherein the antibody comprises a light chain variable region that is at least 80% identical to SEQ ID NO: 15 and a heavy chain variable region that is at least 80% identical to SEQ ID NO: 31, wherein the antibody or the antigen-binding fragment of the antibody comprises:

i) a CDR-L1 comprising SEQ ID NO: 1;

ii) a CDR-L2 comprising SEQ ID NO: 2;

iii) a CDR-L3 comprising SEQ ID NO: 3;

iv) a CDR-H1 comprising SEQ ID NO: 4;

v) a CDR-H2 comprising SEQ ID NO: 5; and

vi) a CDR-H3 comprising SEQ ID NO: 6.