Monoclonal Antibodies Against Pathological Alpha-Synuclein, and Methods Using Same
AssigneeThe Trustees of the University of Pennsylvania
InventorsKelvin C. LUK, Virginia M.Y. LEE, John Q. TROJANOWSKI, Kurt R. BRUNDEN, Dustin COVELL
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Abstract
The present disclosure provides monoclonal antibodies that bind α-Synuclein. In certain aspects, the antibodies preferentially bind to α-Synuclein fibrils over α-Synuclein monomer. In other aspects, the invention comprises a method of treating α-Synucleopathic disease in a subject, comprising administering any of the antibodies of the invention to the subject. In yet other aspects, the invention comprises methods of detecting α-Synuclein fibrils using any of the antibodies of the invention.
Claims26
An isolated monoclonal antibody comprising a light chain variable region (VL) and a heavy chain variable region (VH),
- wherein the VL comprises
- a CDR1 region comprising the amino acid sequence of SEQ ID NOs:
- 1, 11, or 21;
- a CDR2 region comprising the amino acid sequence of SEQ ID NOs:
- 2, 12, or 22;
- and
- a CDR3 region comprising the amino acid sequence of SEQ ID NOs:
- 3, 13, or 23, and
- wherein the VH comprises
- a CDR1 region comprising the amino acid sequence of SEQ ID NOs:
- 6, 16, or 26;
- a CDR2 region comprising the amino acid sequence of SEQ ID NOs:
- 7, 17, or 27;
- and
- a CDR3 region comprising the amino acid sequence of SEQ ID NOs:
- 8, 18, or 28.
4-5. (canceled)
(canceled)
An isolated polynucleotide comprising at least one of the nucleic acid sequences of SEQ ID NOs:
- 5, 10, 15, 20, 25, and 30.
(canceled)
An isolated monoclonal antibody, or fragment thereof, which recognizes a conformational epitope comprising amino acids 130-140 of α-Synuclein (α-Syn), and which affinity for α-Syn fibrils is higher than for α-Syn monomers.
An autonomously replicating or an integrative mammalian cell vector comprising a recombinant nucleic acid encoding an antibody comprising a light chain variable region (VL) and a heavy chain variable region (VH),
- wherein the VL comprises
- a CDR1 region comprising the amino acid sequence of SEQ ID NOs:
- 1, 11, or 21;
- a CDR2 region comprising the amino acid sequence of SEQ ID NOs:
- 2, 12, or 22;
- and
- a CDR3 region comprising the amino acid sequence of SEQ ID NOs:
- 3, 13, or 23;
- and wherein the VH comprises
- a CDR1 region comprising the amino acid sequence of SEQ ID NOs:
- 6, 16, or 26;
- a CDR2 region comprising the amino acid sequence of SEQ ID NOs:
- 7, 17, or 27;
- and
- a CDR3 region comprising the amino acid sequence of SEQ ID NOs:
- 8, 18, or 28.
24-25. (canceled)
(canceled)
Dependencies are inferred from the claim text.