NZ765033B2

NZ765033B2 - Anti-alpha-synuclein antibodies

Info

Publication number: NZ765033B2
Application number: NZ765033A
Authority: NZ
Inventors: Ralph Adams; Terence Seward Baker; Lichtervelde Lorenzo De; Patrick Downey; Daniel John Lightwood; David James Mcmillan; Kerry Louise Tyson
Original assignee: UCB Biopharma SRL
Filing date: 2018-12-13
Publication date: 2025-05-01

Abstract

The present invention relates to antibodies binding alpha synuclein and fragments thereof capable of binding alpha synuclein as a monomer and in fibrils and preventing alpha synuclein aggregation induced by alpha synuclein fibrils. The antibodies of the present invention are for use in the treatment of alpha synucleinopathies, including Parkinson's disease.

Claims

1. An antibody or antigen-binding nt thereof which binds to alpha synuclein, wherein the antibody or antigen-binding fragment comprises: a. a light chain variable region comprising: 5 (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; 10 (ii) a CDR-H2 comprising SEQ ID NO: 5; and (iii) a CDR-H3 sing SEQ ID NO: 6.

2. The antibody or antigen-binding fragment thereof according to claim 1, which binds to an alpha synuclein epitope sing, with reference to SEQ ID NO: 10, residues E123, Y125, E126, M127, P128, S129, E130 and E131, wherein the epitope optionally comprises 15 A124 and G132.

3. The antibody or antigen-binding fragment thereof according to claim 1 or 2, wherein the antibody or antigen-binding nt is chimeric or humanized.

4. The dy according to any one of the preceding claims, wherein the antibody is a full-length antibody. 20 5. The antibody according to claim 4, wherein the full-length antibody is ed from an

5. IgG1, IgG4 or IgG4P.

6. The antigen-binding fragment according to any one of claims 1 to 3, n the antigen- binding fragment is selected from a Fab, a Fab’, a F(ab’)2, an scFv or a dAb.

7. The antibody or antigen-binding fragment thereof according to any one of the preceding 25 claims, n the antibody or antigen-binding fragment thereof comprises: a. a light chain variable region comprising SEQ ID NO: 15 and a heavy chain variable region sing SEQ ID NO: 31; or b. a light chain comprising SEQ ID NO: 17 and a heavy chain comprising SEQ ID

8. SEQ ID NO: 33. 30 8. One or more isolated polynucleotide encoding the antibody or antigen-binding fragment thereof according to any one of claims 1 to 7.

9. The one or more isolated polynucleotide according to claim 8, wherein the one or more polynucleotide s: a. a light chain variable region, wherein the polynucleotide: 21293815_1 (GHMatters) P113601.NZ (i) is at least 90% cal to SEQ ID NO: 16; or (ii) comprises SEQ ID NO: 16; or (iii) consists essentially of SEQ ID NO: 16; b. a heavy chain variable region, n the polynucleotide: 5 (i) is at least 90% identical to SEQ ID NO: 32; or (ii) comprises SEQ ID NO: 32; or (iii) consists essentially of SEQ ID NO: 32; c. a light chain, wherein the polynucleotide: (i) is at least 90% identical to SEQ ID NO: 18; or 10 (ii) comprises SEQ ID NO: 18; or (iii) consists essentially of SEQ ID NO: 18; d. a heavy chain, wherein the polynucleotide: (i) is at least 90% identical to SEQ ID NO: 34; or (ii) comprises SEQ ID NO:34; or 15 (iii) ts essentially of SEQ ID NO: 34.

10. One or more cloning or expression vector comprising one or more polynucleotides according to claim 8 or 9.

11. An isolated or non-human host cell comprising: a. one or more polynucleotides according to claims 8 or 9; or 20 b. one or more expression vectors according to claim 10.

12. A process for producing an antibody or antigen-binding fragment thereof ing to any one of claims 1 to 7, comprising culturing the host cell according to claim 11 under suitable conditions for producing the antibody or antigen-binding nt and isolating the antibody or antigen-binding fragment. 25

13. A pharmaceutical composition comprising the antibody or antigen-binding nt thereof according to any one of claims 1 to 7 and one or more pharmaceutically acceptable carriers, excipients of ts.

14. The antibody or n-binding fragment thereof according to any one of claims 1 to 7 or the pharmaceutical composition according to claim 13 when used in therapy of a non- 30 human animal.

15. Use of the antibody or n-binding fragment thereof according to any one of claims 1 to 7 or the pharmaceutical composition according to claim 13 in the manufacture of a medicament for treating one or more synucleinopathy. 21293815_1 (GHMatters) P113601.NZ

16. The use according to claim 15 wherein the one or more synucleinopathy is selected from Parkinson's disease, optionally an idiopathic or inherited form of Parkinson's disease, dementia with Lewy bodies (DLB), Diffuse Lewy Body Disease , Lewy body variant of Alzheimer's disease (LBVAD), combined Alzheimer's and Parkinson's disease, multiple 5 system atrophy (MSA), and neurodegeneration with brain iron lation type-1 (NBIA-1).

17. The use according to claim 16 wherein the one or more synucleinopathy is Parkinson’s

18. Use of the antibody or antigen-binding fragment thereof according to any one of claims 1 to 7 in the manufacture of a medicament for sing an alpha synucleinopathy, optionally 10 Parkinson’s disease. 21293815_1 (GHMatters) P113601.NZ