Anti-alpha-synuclein antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-2016108113-A1
Application number	US-201514884542-A
Country	US
Kind code	A1
Filing date	Oct 15, 2015
Priority date	Oct 16, 2014
Publication date	Apr 21, 2016
Grant date	—

Abstract

The present invention relates to anti-alpha-synuclein (anti-α-synuclein) antibodies and methods of using the same.

First claim

What is claimed is:

1 . An isolated anti-α-synuclein antibody comprising three heavy chain hypervariable regions (HVR-H1, HVR-H2, and HVR-H3) and three light chain hypervariable regions (HVR-L1, HVR-L2, and HVR-L3), wherein:
(a) HVR-H1 comprises the amino acid sequence of SEQ ID NO:9;
(b) HVR-H2 comprises the amino acid sequence of SEQ ID NO:10;
(c) HVR-H3 comprises the amino acid sequence of SEQ ID NO:11;
(d) HVR-L1 comprises the amino acid sequence of SEQ ID NO:6;
(e) HVR-L2 comprises the amino acid sequence of SEQ ID NO:7; and
(f) HVR-L3 comprises the amino acid sequence of SEQ ID NO:8.

2 . An isolated anti-α-synuclein antibody comprising three light chain hypervariable regions (HVR-L1, HVR-L2, and LVR-L3), wherein:
(a) HVR-L1 comprises the amino acid sequence of SEQ ID NO:6;
(b) HVR-L2 comprises the amino acid sequence of SEQ ID NO:7; and
(c) HVR-L3 comprises the amino acid sequence of SEQ ID NO:8.

3 . An isolated anti-α-synuclein antibody comprising three heavy chain hypervariable regions (HVR-H1, HVR-H2, and HVR-H3), wherein:
(a) HVR-H1 comprises the amino acid sequence of SEQ ID NO:9;
(b) HVR-H2 comprises the amino acid sequence of SEQ ID NO:10; and
(c) HVR-H3 comprises the amino acid sequence of SEQ ID NO:11.

4 . The isolated anti-α-synuclein antibody of claim 1 , comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:3, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:2.

5 . The isolated anti-α-synuclein antibody of claim 1 , comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO:2.

6 . The isolated anti-α-synuclein antibody of claim 1 , comprising a heavy chain variable region comprises the amino acid sequence of SEQ ID NO:3.

7 . An isolated anti-α-synuclein antibody comprising three heavy chain hypervariable regions (HVR-H1, HVR-H2, and HVR-H3) and three light chain hypervariable regions (HVR-L1, HVR-L2, and HVR-L3), wherein:
(a) HVR-H1 comprises the amino acid sequence of SEQ ID NO:15;
(b) HVR-H2 comprises the amino acid sequence of SEQ ID NO:16;
(c) HVR-H3 comprises the amino acid sequence of SEQ ID NO:17;
(d) HVR-L1 comprises the amino acid sequence of SEQ ID NO:12;
(e) HVR-L2 comprises the amino acid sequence of SEQ ID NO:13; and
(f) HVR-L3 comprises the amino acid sequence of SEQ ID NO:14.

8 . An isolated anti-α-synuclein antibody comprising three light chain hypervariable regions (HVR-L1, HVR-L2, and LVR-L3), wherein:
(a) HVR-L1 comprises the amino acid sequence of SEQ ID NO:12;
(b) HVR-L2 comprises the amino acid sequence of SEQ ID NO:13; and
(c) HVR-L3 comprises the amino acid sequence of SEQ ID NO:14.

9 . An isolated anti-α-synuclein antibody comprising three heavy chain hypervariable regions (HVR-H1, HVR-H2, and HVR-H3), wherein:
(a) HVR-H1 comprises the amino acid sequence of SEQ ID NO:15;
(b) HVR-H2 comprises the amino acid sequence of SEQ ID NO:16; and
(c) HVR-H3 comprises the amino acid sequence of SEQ ID NO:17.

10 . The isolated anti-α-synuclein antibody of claim 7 , comprising a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region comprises the amino acid sequence of SEQ ID NO:5, and the light chain variable region comprises the amino acid sequence of SEQ ID NO:4.

11 . The isolated anti-α-synuclein antibody of claim 7 , comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO:4.

12 . The isolated anti-α-synuclein antibody of claim 7 , comprising a heavy chain variable region comprises the amino acid sequence of SEQ ID NO:5.

13 . The antibody of claim 1 or claim 7 , wherein the antibody is a monoclonal antibody.

14 . The antibody of claim 1 or claim 7 , wherein the antibody is a human, humanized, or chimeric antibody.

15 . The antibody of claim 1 or claim 7 , wherein the antibody binds an α-synuclein selected from the group consisting of monomeric α-synuclein and oligomeric α-synuclein.

16 . An isolated nucleic acid encoding the antibody of claim 1 or claim 7 .

17 . An isolated nucleic acid encoding the antibody of claim 4 or claim 10 .

18 . A host cell comprising the nucleic acid of claim 16 .

19 . A method of producing an antibody comprising culturing the host cell of claim 18 so that the antibody is produced.

20 . An antibody that competes with the antibody of claim 1 or claim 4 for binding to human α-synuclein.

21 . An antibody that binds to the same epitope in human α-synuclein as the antibody of claim 1 or claim 4 .

22 . An antibody that competes with the antibody of claim 7 or claim 10 for binding to human α-synuclein.

23 . An antibody that binds to the same epitope in human α-synuclein as the antibody of claim 7 or claim 10 .

24 . An isolated antibody that binds to human α-synuclein, wherein the antibody binds a region or epitope of α-synuclein comprising amino acid residues 5-43 of human α-synuclein.

25 . An isolated antibody that binds to human α-synuclein, wherein the antibody binds a region or epitope of α-synuclein comprising amino acid residues 5-78 of human α-synuclein.

26 . An isolated antibody that binds to human α-synuclein, wherein the antibody binds a region or epitope of α-synuclein comprising amino acid residues 37-51 of human α-synuclein.

27 . An isolated antibody that binds to human α-synuclein, wherein the antibody binds a region or epitope of α-synuclein comprising amino acid residues 104-118 of human α-synuclein.

28 . A pharmaceutical formulation comprising the antibody of claim 1 or claim 4 and a pharmaceutically acceptable carrier.

29 . A pharmaceutical formulation comprising the antibody of claim 7 or claim 10 and a pharmaceutically acceptable carrier.

30 . The antibody of claim 1 or claim 7 for use in treating, preventing, or delaying the onset of a disorder selected from the group consisting of a synucleinopathy, Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies, Lewy body disease, juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease), multiple system atrophy, pure autonomic failure, and neurodegeneration with brain iron accumulation type-1.

31 . The antibody of claim 4 or claim 10 for use in treating, preventing, or delaying the onset of a disorder selected from the group consisting of a synucleinopathy, Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies, Lewy body disease, juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease), multiple system atrophy, pure autonomic failure, and neurodegeneration with brain iron accumulation type-1.

32 . The antibody of claim 1 or claim 7 for use as a medicament.

33 . The antibody of claim 4 or claim 10 for use as a medicament.

34 . A method for treating an individual having a disorder selected from the group consisting of a synucleinopathy, Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies, Lewy body disease, juvenile-onset generalized neuroaxonal dystrophy (Hallervorden-Spatz disease), multiple system atrophy, pure autonomic failure,

Assignees

• Genentech Inc

Inventors

• Ayalon Gai
• Maurer Till

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61K2039/505

  comprising antibodies · CPC title