Antibodies binding alpha-synuclein fibrils

Abstract

The present disclosure is based, in part, on the discovery of antibodies, such as BAN0805, that selectively target human alpha-synuclein aggregates, such as oligomers / fibrils. BAN0805 has a lower propensity to bind to undesired monomeric alpha-synuclein targets compared to mouse monoclonal antibody mAb47.

Claims

1. An anti-α-synuclein antibody comprising a heavy chain containing the amino acid sequence of SEQ ID NO: 1 and a light chain containing the amino acid sequence of SEQ ID NO:

2.

2. The anti-α-synuclein antibody as described in claim 1, wherein the antibody belongs to the IgG isotype.

3. The anti-α-synuclein antibody as described in claim 1, wherein the antibody belongs to the IgG4 isotype.

4. The anti-α-synuclein antibody according to any one of claims 1 to 3, wherein the antibody binds to the K+ fibrillar form of α-synuclein. D The value is the K value in the monomeric form of α-synuclein. D The value is at most 1 / 110,000.

5. The anti-α-synuclein antibody according to any one of claims 1 to 3, wherein the antibody binds to the K+ fibrillar form of α-synuclein. D The value is at most 18 pM, and it binds to the monomeric form of α-synuclein, K. D The value is at least 2200 nM.

6. The anti-α-synuclein antibody of claim 4, wherein the antibody binds to K+ in the fibrillary form of α-synuclein. D And the K antibody binds to the monomeric form of α-synuclein. D Measured using SPR.

7. The anti-α-synuclein antibody of claim 5, wherein the antibody binds to K+ in the fibrillary form of α-synuclein. D And the K antibody binds to the monomeric form of α-synuclein. D Measured using SPR.

8. An anti-α-synuclein antibody comprising a heavy chain containing the amino acid sequence of SEQ ID NO: 3 and a light chain containing the amino acid sequence of SEQ ID NO:

4.

9. The anti-α-synuclein antibody of claim 8, wherein the antibody comprises two heavy chains and two light chains.

10. One or more nucleic acids encoding an antibody as described in any one of claims 1 to 9.

11. One or more nucleic acids as described in claim 10, wherein (a) The one or more nucleic acids contain the sequences of SEQ ID NO: 11 and 12. (b) The one or more nucleic acids contain the sequences of SEQ ID NO: 13 and 14. (c) The one or more nucleic acids comprise the sequences of SEQ ID NO: 17 and 18, or (d) The one or more nucleic acids contain the sequences of SEQ ID NO: 19 and 20.

12. One or more vectors comprising the nucleic acid as described in any one of claims 10 to 11.

13. A host cell comprising the nucleic acid as described in any one of claims 10 to 11.

14. A host cell comprising one or more vectors as described in claim 12.

15. A host cell expressing an antibody as described in any one of claims 1 to 9.

16. A composition comprising an anti-α-synuclein antibody as described in any one of claims 1 to 9 and a pharmaceutically acceptable carrier.

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