Antibodies directed against amyloid-beta peptide and methods using same

• US 8,398,978 B2
• Filed: 03/15/2010
• Issued: 03/19/2013
• Est. Priority Date: 04/29/2005
• Status: Expired due to Fees

• Current Assignee: Rinat Neuroscience Corp. (Pfizer Inc.)
• Original Assignee: Rinat Neuroscience Corp. (Pfizer Inc.)
• Inventors: Rosenthal, Arnon, Pons, Jaume, Ho, Wei-Hsien
• Primary Examiner(s): Emch, Gregory S
• Application Number:
  US12/724,343
• Publication Number:
  US 20110044985A1
• Time in Patent Office: 1,100 Days
• Field of Search: None
• US Class Current: 424/139.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 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 Class Codes: A61P 31/18 for HIV
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 2317/14 Specific host cells or culture conditions, e.g. components, pH or temperature
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/41 Glycosylation, sialylation, or fucosylation
• CPC Class Codes: C07K 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/522 CH1 domain
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

Methods of using antibodies directed to the C-terminal side of β-amyloid peptide for diagnosing and treatment of Alzheimer'"'"'s disease and Aβ peptide associated diseases are described.

Claims

1. A method for treating a disease associated with aberrant deposition of β

-amyloid in a subject, comprising administering to the subject an effective amount of an antibody that specifically binds to a β

-amyloid peptide or an aggregated form of a β

-amyloid peptide, wherein the antibody binds to an epitope on Aβ

_1-40 that includes amino acids 25-34 and 40, wherein the antibody binds to Aβ

_1-40 with higher affinity than its binding to Aβ

_1-42 and Aβ

_1-43, wherein the antibody binds to Aβ

_22-37 with a K_D of less than 1 μ

M, and wherein the antibody comprises a heavy chain variable region comprising three CDRs at least 97% identical to the three CDRs from the heavy chain variable region shown in SEQ ID NO;

1, and a light chain variable region comprising three CDRs at least 96% identical to the three CDRs from the light chain variable region shown in SEQ ID NO;

2.

2. The method of claim 1, wherein the antibody comprises a Fab fragment which binds Aβ

_1-40 with an affinity of about 10 nM or less.

3. The method of claim 1, wherein the antibody treats, inhibits or delays development of a disease associated with altered Aβ

or β

APP expression or accumulation of Aβ

peptide.

4. The method of claim 1, wherein the disease is Alzheimer'"'"'s disease, multi-infarct dementia, mild cognitive impairment, cerebral amyloid angiopathy, Down'"'"'s syndrome, Parkinson'"'"'s disease, Creutzfeld-Jakob, or dementia with Lewy body.

5. The method of claim 1, wherein the method suppresses formation of or reduces amyloid plaques in the subject.

6. The method of claim 1, wherein the method improves cognition or reverses cognitive decline associated with amyloid deposit of Aβ

in the subject.

7. A method for treating Alzheimer'"'"'s disease, multi-infarct dementia, mild cognitive impairment, cerebral amyloid angiopathy, Down'"'"'s syndrome, Parkinson'"'"'s disease, Creutzfeld-Jakob, or dementia with Lewy body, comprising administering to a subject an effective amount of an antibody that specifically binds to a β

-amyloid peptide or an aggregated form of a β

-amyloid peptide, wherein the antibody binds to an epitope on Aβ

_1-40 that includes amino acids 25-34 and 40, wherein the antibody binds to an epitope on Aβ

_1-40 with higher affinity than its binding to Aβ

_1-42 and Aβ

_1-43, wherein the antibody binds to Aβ

_22-37 with a K_D of less than 1 μ

M, and wherein the antibody comprises a heavy chain variable region comprising three CDRs at least 97% identical to the three CDRs from the heavy chain variable region shown in SEQ ID NO;

1, and a light chain variable region comprising three CDRs at least 96% identical to the three CDRs from the light chain variable region shown in SEQ ID NO;

2.

8. The method of claim 7, wherein the antibody comprises a Fab fragment which binds Aβ

_1-40 with an affinity of about 10 nM or less.

9. The method of claim 7, wherein the antibody treats, inhibits or delays development of a disease associated with altered Aβ

or β

APP expression or accumulation of Aβ

peptide.

10. The method of claim 7, wherein the method suppresses formation of or reduces amyloid plaques in the subject.

11. The method of claim 7, wherein the method improves cognition or reverses cognitive decline associated with amyloid deposit of Aβ

in the subject.

12. A method for treating Alzheimer'"'"'s disease, multi-infarct dementia, mild cognitive impairment, cerebral amyloid angiopathy, Down'"'"'s syndrome, Parkinson'"'"'s disease, Creutzfeld-Jakob, or dementia with Lewy body, comprising administering to a subject an effective amount of an antibody, wherein the antibody comprises a heavy chain variable region comprising the three CDRs set forth in the amino acid sequences of SEQ ID NO:

3, SEQ ID NO;

4, and SEQ ID NO;

5, and a light chain variable region comprising the three CDRs set forth in the amino acid sequences of SEQ ID NO;

6, SEQ ID NO;

7, and SEQ ID NO;

8.

13. The method of claim 12, wherein the antibody comprises a heavy chain constant region comprising a Fc region, wherein the heavy chain constant region has impaired effector function.

14. The method of claim 12, wherein the antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

1, and a light chain variable region comprising the amino acid sequence of SEQ ID NO;

2.

15. The method of claim 12, wherein the antibody comprises a heavy chain amino acid sequence of SEQ ID NO:

11, and a light chain amino acid sequence of SEQ ID NO;

12.

16. The method of claim 12, wherein the antibody comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:

1.

17. The method of claim 12, wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO:

2.

18. The method of claim 12, wherein the method suppresses formation of or reduces amyloid plaques in the subject.

19. The method of claim 12, wherein the method improves cognition or reverses cognitive decline associated with amyloid deposit of Aβ

in the subject.