Methods and compositions for neural disease immunotherapy

Patent metadata

Field	Value
Publication number	US-9453079-B2
Application number	US-201414292461-A
Country	US
Kind code	B2
Filing date	May 30, 2014
Priority date	Nov 10, 2010
Publication date	Sep 27, 2016
Grant date	Sep 27, 2016

Abstract

The invention provides antibodies to specific neural proteins and methods of using the same.

First claim

What is claimed is:

1. A method of treating an individual having a neurological disease or disorder characterized by amyloid β pathology, comprising administering to the individual an effective amount of an antibody or fragment thereof that binds to β-site amyloid precursor protein cleaving enzyme 1 (BACE1), wherein the antibody or fragment thereof comprises
a) an HVR-H1 comprising the amino acid sequence GFTFX 13 GYX 14 IH (SEQ ID NO:26), wherein X 13 =S or L and X 14 =A or G;
b) an HVR-H2 comprising the amino acid sequence GWISPAGGSTDYADSVKG (SEQ ID NO: 24);
c) an HVR-H3 comprising the amino acid sequence of GPFSPWVMDY (SEQ ID NO: 25),
d) an HVR-L1 comprising the amino acid sequence of RASQX 1 VX 2 X 3 X 4 X 5 A (SEQ ID NO:17), wherein X 1 =D or V; X 2 =S or A; X 3 =T or N; X 4 =S or A; X 5 =V or L;
e) an HVR-L2 comprising the amino acid sequence of X 6 ASFLYS (SEQ ID NO:18) wherein X 6 =S or L; and
f) an HVR-L3 comprising the amino acid sequence of QQX 7 X 8 X 9 X 10 X 11 X 12 T (SEQ ID NO:19), wherein X 7 =S, F, G, D or Y; X 8 =Y, P, S, or A; X 9 =T or N; X 10 =T, Y, D or S; X 11 =P or L; X 12 =P or T;

wherein the antibody reduces or inhibits the activity of BACE1.

2. The method of claim 1 , wherein the neurological disease or disorder is selected from the group consisting of Alzheimer's disease, stroke, traumatic brain injury, Lewy body disease, Parkinson's disease, and glaucoma.

3. A method of reducing brain amyloid β levels in a patient in need thereof, comprising administering to the individual an effective amount of an antibody or fragment thereof that binds to β-site amyloid precursor protein cleaving enzyme 1 (BACE1), wherein the antibody or fragment thereof comprises
a) an HVR-H1 comprising the amino acid sequence GFTFX 13 GYX 14 IH (SEQ ID NO:26), wherein X 13 =S or L and X 14 =A or G;
b) an HVR-H2 comprising the amino acid sequence GWISPAGGSTDYADSVKG (SEQ ID NO: 24);
c) an HVR-H3 comprising the amino acid sequence of GPFSPWVMDY (SEQ ID NO: 25),
d) an HVR-L1 comprising the amino acid sequence of RASQX 1 VX 2 X 3 X 4 X 5 A (SEQ ID NO:17), wherein X 1 =D or V; X 2 =S or A; X 3 =T or N; X 4 =S or A; X 5 =V or L;
e) an HVR-L2 comprising the amino acid sequence of X 6 ASFLYS (SEQ ID NO:18) wherein X 6 =S or L; and
f) an HVR-L3 comprising the amino acid sequence of QQX 7 X 8 X 9 X 10 X 11 X 12 T (SEQ ID NO:19), wherein X 7 =S, F, G, D or Y; X 8 =Y, P, S, or A; X 9 =T or N; X 10 =T, Y, D or S; X 11 =P or L; X 12 =P or T;

wherein the antibody reduces or inhibits the activity of BACE1.

4. A method of inhibiting amyloid plaque formation in a patient suffering from a neurological disease or disorder characterized by amyloid β pathology, comprising administering to the patient an effective amount of an antibody or fragment thereof that binds to β-site amyloid precursor protein cleaving enzyme 1 (BACE1), wherein the antibody or fragment thereof comprises
a) an HVR-H1 comprising the amino acid sequence GFTFX 13 GYX 14 IH (SEQ ID NO:26), wherein X 13 =S or L and X 14 =A or G;
b) an HVR-H2 comprising the amino acid sequence GWISPAGGSTDYADSVKG (SEQ ID NO: 24);
c) an HVR-H3 comprising the amino acid sequence of GPFSPWVMDY (SEQ ID NO: 25),
d) an HVR-L1 comprising the amino acid sequence of RASQX 1 VX 2 X 3 X 4 X 5 A (SEQ ID NO:17), wherein X 1 =D or V; X 2 =S or A; X 3 =T or N; X 4 =S or A; X 5 =V or L;
e) an HVR-L2 comprising the amino acid sequence of X 6 ASFLYS (SEQ ID NO:18) wherein X 6 =S or L; and
f) an HVR-L3 comprising the amino acid sequence of QQX 7 X 8 X 9 X 10 X 11 X 12 T (SEQ ID NO:19), wherein X 7 =S, F, G, D or Y; X 8 =Y, P, S, or A; X 9 =T or N; X 10 =T, Y, D or S; X 11 =P or L; X 12 =P or T;

wherein the antibody reduces or inhibits the activity of BACE1.

5. A method of reducing amyloid-β (Aβ) protein in a patient in need thereof comprising administering to the patient an effective amount of an antibody or fragment thereof that binds to β-site amyloid precursor protein cleaving enzyme 1 (BACE1), wherein the antibody or fragment thereof comprises
a) an HVR-H1 comprising the amino acid sequence GFTFX 13 GYX 14 IH (SEQ ID NO:26), wherein X 13 =S or L and X 14 =A or G;
b) an HVR-H2 comprising the amino acid sequence GWISPAGGSTDYADSVKG (SEQ ID NO: 24);
c) an HVR-H3 comprising the amino acid sequence of GPFSPWVMDY (SEQ ID NO: 25),
d) an HVR-L1 comprising the amino acid sequence of RASQX 1 VX 2 X 3 X 4 X 5 A (SEQ ID NO:17), wherein X 1 =D or V; X 2 =S or A; X 3 =T or N; X 4 =S or A; X 5 =V or L;
e) an HVR-L2 comprising the amino acid sequence of X 6 ASFLYS (SEQ ID NO:18) wherein X 6 =S or L; and
f) an HVR-L3 comprising the amino acid sequence of QQX 7 X 8 X 9 X 10 X 11 X 12 T (SEQ ID NO:19), wherein X 7 =S, F, G, D or Y; X 8 =Y, P, S, or A; X 9 =T or N; X 10 =T, Y, D or S; X 11 =P or L; X 12 =P or T;

wherein the antibody reduces or inhibits the activity of BACE1.

6. The method of claim 5 , wherein the patient is suffering from a neurological disease or disorder.

7. The method of claim 6 , wherein the neurological disease or disorder is selected from the group consisting of: Alzheimer's disease, stroke, traumatic brain injury and glaucoma.

8. The method of claim 1 , wherein the HVR-H1 comprises an amino acid sequence selected from SEQ ID NO:22 and SEQ ID NO:23.

9. The method of claim 3 , wherein the HVR-H1 comprises an amino acid sequence selected from SEQ ID NO:22 and SEQ ID NO:23.

10. The method of claim 4 , wherein the HVR-H1 comprises an amino acid sequence selected from SEQ ID NO:22 and SEQ ID NO:23.

11. The method of claim 5 , wherein the HVR-H1 comprises an amino acid sequence selected from SEQ ID NO:22 and SEQ ID NO:23.

12. The method of claim 1 , wherein the antibody comprises a VH chain having an amino acid sequence selected from SEQ ID NOs: 20 and 21.

13. The method of claim 3 , wherein the antibody comprises a VH chain having an amino acid sequence selected from SEQ ID NOs: 20 and 21.

14. The method of claim 4 , wherein the antibody comprises a VH chain having an amino acid sequence selected from SEQ ID NOs: 20 and 21.

15. The method of claim 5 , wherein the antibody comprises a VH chain having an amino acid sequence selected from SEQ ID NOs: 20 and 21.

16. The method of claim 1 , wherein the HVR-L1 comprises an amino acid sequence of SEQ ID NO:7 or SEQ ID NO:8; the HVR-L2 comprises an amino acid sequence of SEQ ID NO:9 or SEQ ID NO:10; and the HVR-L3 comprises an amino acid sequence selected from SEQ ID NOs:11-16.

17. The method of claim 3 , wherein the HVR-L1 comprises an amino acid sequence of SEQ ID NO:7 or SEQ ID NO:8; the HVR-L2 comprises an amino acid sequence of SEQ ID NO:9 or SEQ ID NO:10; and the HVR-L3 comprises an amino acid sequence selected from SEQ ID NOs:11-16.

18. The method of claim 4 , wherein the HVR-L1 comprises an amino acid sequence of SEQ ID NO:7 or SEQ ID NO:8; the HVR-L2 comprises an amino acid sequence of SEQ ID NO:9 or SEQ ID NO:10; and the HVR-L3 comprises an amino acid sequence selected from SEQ ID NOs:11-16.

19. The method of claim 5 , wherein the HVR-L1 comprises an amino acid sequence of SEQ ID NO:7 or SEQ ID NO:8; the HVR-L2 comprises an amino acid sequence of SEQ ID NO:9 or SEQ ID NO:10; and the HVR-L3 comprises an amino acid sequence selected from SEQ ID NOs:11-16.

20. The method of claim 1 , wherein the antibody comprises a VL chain sequence having an amino acid sequence selected from SEQ ID NOs: 1-6.

21. The method of claim 3 , wherein the antibody comprises a VL chain sequence having an amin

Assignees

• Genentech Inc

Inventors

• Atwal Jasvinder
• Chen Yongmei
• Chiu Cecilia Pui Chi
• Lazarus Robert A
• Wang Weiru
• Watts Ryan J
• Wu Yan
• Zhang Yingnan

Classifications

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P43/00

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

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P25/14

  for treating abnormal movements, e.g. chorea, dyskinesia · CPC title

• A61P25/02

  for peripheral neuropathies · CPC title