Use of an Anti-Alpha-Synuclein Antibody to Diagnose an Elevated Level of Alpha-Synuclein in the Brain
AssigneeBiogen International Neuroscience GmbH
InventorsAndreas Weihofen, Thomas Engber, Jan Grimm
Life of this patent
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Abstract
This disclosure relates to the use of anti-α-synuclein antibody to diagnose an elevated level of α-synuclein in the brain. Specifically, the disclosure relates to the method of assessing the levels of α-synuclein in a blood plasma or CSF following administration to the test subject of an anti-α-synuclein antibody or antigen-binding fragment thereof, which can bind α-synuclein with sufficient activity to alter the net efflux of α-synuclein from brain to blood, or from brain to CSF.
Claims29
A method of diagnosing an elevated level of α-synuclein in the brain of a test human subject, the method comprising:
- (a) peripherally administering an anti-α-synuclein antibody or antigen-binding fragment thereof to the test subject,
- wherein the antibody or antigen binding fragment thereof can bind α-synuclein with sufficient affinity to alter the net efflux of α-synuclein from brain to blood or cerebrospinal fluid (CSF),
- and wherein the anti-α-synuclein antibody or antigen binding fragment thereof comprises a heavy chain variable region (VH) comprising VH complementarity determining regions (CDRs), VH CDR1, VH CDR2, and VH CDR3 with the amino acid sequence set forth in SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, and a light chain variable region (VL) comprising VL CDRs, VL CDR1, VL CDR2, and VL CDR3 with the amino acid sequence set forth in SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9, respectively;
- and
- (b) assaying the level of α-synuclein in a blood plasma or CSF sample obtained from the test subject at a specified interval following peripheral administration to the test subject of the anti-α-synuclein antibody or antigen-binding fragment thereof,
- wherein a difference or similarity between the level of α-synuclein in the blood plasma or CSF sample and a reference standard correlates with the level of α-synuclein in the brain of the test subject.
-3. (canceled)
A method of diagnosing an elevated level of α-synuclein in the brain of a test human subject, the method comprising:
- assaying the level of α-synuclein in a blood plasma or cerebrospinal fluid (CSF) sample obtained from the test subject at a specified interval following peripheral administration to the test subject of an anti-α-synuclein antibody or antigen-binding fragment thereof,
- wherein the antibody or antigen binding fragment thereof can bind α-synuclein with sufficient affinity to alter the net efflux of α-synuclein from brain to CSF,
- wherein the antibody or antigen binding fragment thereof comprises a heavy chain variable region (VH) comprising VH complementarity determining regions (CDRs), VH CDR1, VH CDR2, and VH CDR3 with the amino acid sequence set forth in SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, and a light chain variable region (VL) comprising VL CDRs, VL CDR1, VL CDR2, and VL CDR3 with the amino acid sequence set forth in SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9, respectively;
- and
- wherein a difference or similarity between the level of α-synuclein in the blood plasma or CSF sample and a reference standard correlates with the level of α-synuclein in the brain of the test subject.
-7. (canceled)
A method of tracking the α-synuclein level in the brain of a human subject being treated for a synucleinopathic disease, the method comprising assaying the level of α-synuclein in the subject's blood plasma or cerebrospinal fluid (CSF) at a specified time following peripheral administration of an anti-α-synuclein antibody or antigen-binding fragment thereof,
- wherein the anti-α-synuclein antibody or antigen binding fragment thereof comprises:
- (i) a heavy chain variable region (VH) comprising VH complementarity determining regions (CDRs), VH CDR1, VH CDR2, and VH CDR3 with the amino acid sequence set forth in SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively and a light chain variable region (VL) comprising VL CDRs, VL CDR1, VL CDR2, and VL CDR3 with the amino acid sequence set forth in SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9, respectively;
- or
- (ii) a VH with the amino acid sequence set forth in SEQ ID NO:2 and a VL with the amino acid sequence set forth in SEQ ID NO:3;
- and
- wherein the anti-α-synuclein antibody or fragment thereof can bind α-synuclein with sufficient affinity to alter the net efflux of the α-synuclein from brain to blood or from brain to CSF;
- and wherein the α-synuclein level in the subject's blood plasma or CSF correlates with the level in the human subject's brain.
(canceled)
-24. (canceled)
A kit comprising:
- an anti-α-synuclein antibody or antigen binding fragment thereof, comprising a heavy chain variable region (VH) comprising VH complementarity determining regions (CDRs), VH CDR1, VH CDR2, and VH CDR3 with the amino acid sequence set forth in SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6, respectively, and a light chain variable region (VL) comprising VL CDRs, VL CDR1, VL CDR2, and VL CDR3 with the amino acid sequence set forth in SEQ ID NO:7, SEQ ID NO:8, and SEQ ID NO:9, respectively;
- and
- instructions for use of the anti-α-synuclein antibody or antigen binding fragment thereof to diagnose an elevated level of α-synuclein in the brain.
Dependencies are inferred from the claim text.