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US 12,404,321 B2Granted
Conformation-specific epitopes in alpha-synuclein, antibodies thereto and methods related thereof
AssigneesThe University of British Columbia, ProMIS Neurosciences Inc.
InventorsNeil R. Cashman, Steven S. Plotkin, Xubiao Peng, Johanne Kaplan
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Abstract
The disclosure pertains to conformational epitopes in alpha-synuclein, antibodies thereto and methods of making and using immunogens and antibodies specific thereto. In particular antibodies raised to cyclic compounds comprising at least 3 amino acids of EKTKEQ (SEQ ID NO: 1) selectively recognize misfolded oligomeric alpha-synuclein and are able to inhibit alpha-synuclein propagation and toxicity.
Claims18
An antibody that binds an epitope in EKTKEQ (SEQ ID NO:
- 1), in misfolded oligomeric alpha-Syn polypeptide,
- wherein the antibody comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprising complementarity determining regions CDR-H1, CDR-H2 and CDR-H3, and the light chain variable region comprising complementarity determining regions CDR-L1, CDR-L2 and CDR-L3,
- wherein the complementarity determining regions CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2 and CDR-L3 have amino acid sequences of SEQ ID NOs:
- 61-66, respectively, SEQ ID NOs:
- 67-72, respectively, SEQ ID NOs:
- 73-78, respectively, SEQ ID NOs:
- 79-81, 76, 77, and 84, respectively, SEQ ID NOs:
- 91-94, 71, and 96, respectively, or amino acid sequences of SEQ ID NOs:
- 180, 181, 182, 183, 77, and 184 respectively.
6 more elements
Dependencies are inferred from the claim text.