Protofibril-binding antibodies and their use in therapeutic and diagnostic methods for parkinson's disease, dementia with lewy bodies and other α-synucleinopathies

摘要

In an in vivo method for detecting α-synuclein protofibrils in human tissue, an antibody or fragment thereof is administered to a human. The antibody or fragment is labelled with a detectable label. A complex formed between the antibody or fragment and α-synuclein protofibrils in the human tissue is detected. The antibody or fragment has high affinity for human α-synuclein protofibrils and low affinity for α-synuclein monomers and has a combination of three specified variable heavy (VH) CDR sequences and three specified variable light (VL) CDR sequences.

主权项

1. An in vivo method for detecting α-synuclein protofibrils in human tissue, comprising administering an antibody or fragment thereof to a human, wherein the antibody or fragment thereof is labelled with a detectable label, and detecting a complex formed between the antibody or fragment thereof and α-synuclein protofibrils in the human tissue, wherein the antibody or fragment thereof has high affinity for human α-synuclein protofibrils and low affinity for α-synuclein monomers and has a combination of three variable heavy (VH) CDR sequences and three variable light (VL) CDR sequences selected from the following combinations:
SEQ ID NOS: 22, 28, 35, 41, 47 and 50, SEQ ID NOS: 23, 29, 36, 42, 47 and 50, SEQ ID NOS: 24, 30, 37, 43, 48 and 51, SEQ ID NOS: 25, 31, 38, 44, 47 and 52, SEQ ID NOS: 26, 32, 39, 45, 47 and 53, SEQ ID NOS: 23, 33, 37, 43, 48 and 54, and SEQ ID NOS: 27, 34, 40, 46, 49 and 55.