Antibodies directed against amyloid-beta peptide

• US 7,927,594 B2
• Filed: 08/01/2005
• Issued: 04/19/2011
• Est. Priority Date: 07/30/2004
• Status: Expired due to Fees

• Current Assignee: Rinat Neuroscience Corp. (Pfizer Inc.)
• Original Assignee: Rinat Neuroscience Corp. (Pfizer Inc.)
• Inventors: Pons, Jaume, Grimm, Jan Markus, Rosenthal, Arnon, Ho, Wei-Hsien
• Primary Examiner(s): Kolker; Daniel E
• Assistant Examiner(s): Emch; Gregory S
• Application Number:
  US11/194,989
• Publication Number:
  US 20060057701A1
• Time in Patent Office: 2,087 Days
• Field of Search: None
• US Class Current: 424/152.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 39/00 Medicinal preparations containing antigens or antibodies materials for immunoassay G01N33/53
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• 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 2317/55 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

Monoclonal antibody 9TL and antibodies derived from 9TL directed against amyloid-beta peptide and methods of using same for diagnosing and treatment of Alzheimer'"'"'s disease and Aβ peptide associated diseases are described. Methods of using antibodies directed against amyloid-beta peptide having impaired effector function for treatment of Alzheimer'"'"'s disease and Aβ peptide associated diseases are also described.

Claims

1. An isolated antibody comprising a heavy chain variable region comprising:

(a) a CDR1 comprising the amino acid sequence of SEQ ID NO;

3;

(b) a CDR2 comprising the amino acid sequence of SEQ ID NO;

4; and

(c) a CDR3 comprising the amino acid sequence of SEQ ID NO;

5; and

a light chain variable region comprising;

(d) a CDR1 comprising the amino acid sequence of SEQ ID NO;

6;

(e) a CDR2 comprising the amino acid sequence of SEQ ID NO;

7; and

(f) a CDR3 comprising the amino acid sequence of SEQ ID NO;

8;

wherein the antibody specifically binds to an Aβ

peptide.

2. The isolated antibody of claim 1, wherein the antibody is a humanized antibody.

3. A pharmaceutical composition comprising (a) the antibody of claim 1, and (b) a pharmaceutically acceptable excipient.

4. A kit comprising the antibody of claim 1.

5. The isolated antibody of claim 1, wherein the antibody specifically binds to an epitope on Aβ

_1-40 that includes amino acid 39 and/or 40.

6. The isolated antibody of claim 1, wherein the antibody binds to Aβ

_1-40 with higher affinity than to Aβ

_1-42 or Aβ

_1-43.

7. The isolated antibody of claim 1, wherein the antibody comprises an Fc region having impaired effector function.

8. The antibody of claim 7, wherein the Fc region of the antibody is not N-glycosylated or has an N-glycosylation pattern that is altered with respect to a native Fc region.

9. The isolated antibody of claim 7, wherein the Fc region of the antibody comprises a mutation within the N-glycosylation recognition sequence, whereby the Fc region is not N-glycosylated.

10. The isolated antibody of claim 7, wherein the Fc region of the antibody is the Fc region of a human heavy chain IgG2a comprising the amino acid mutation from alanine to serine at position 330 and from proline to serine at position 331, wherein the amino acid position is based on Kabat numbering with reference to human wildtype IgG2a sequence.

11. The isolated antibody of claim 1, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:

1.

12. The isolated antibody of claim 1, wherein the light chain variable region comprises the amino acid sequence shown in SEQ ID NO:

2.

13. The isolated antibody of claim 12, wherein the heavy chain variable region comprises the amino acid sequence shown in SEQ ID NO:

1.

14. The isolated antibody of claim 13, wherein the heavy chain comprises the amino acid sequence shown in SEQ ID NO:

11; and

the light chain comprises the amino acid sequence shown in SEQ ID NO;

12.

15. The isolated antibody of claim 12, wherein the heavy chain variable region consists of the amino acid sequence shown in SEQ ID NO:

1 and the light chain variable region consists of the amino acid sequence shown in SEQ ID NO;

2.

16. A pharmaceutical composition comprising (a) the antibody of claim 15, and (b) a pharmaceutically acceptable excipient.

17. A kit comprising the antibody of claim 15.

18. The isolated antibody of claim 15 wherein the Fc region of the antibody is the Fc region of a human heavy chain IgG2a comprising the amino acid mutation from alanine to serine at position 330 and from proline to serine at position 331, wherein the amino acid position is based on Kabat numbering with reference to human wildtype IgG2a sequence.

19. The isolated antibody of claim 12, wherein the heavy chain consists of the amino acid sequence shown in SEQ ID NO:

11 and the light chain consists of the amino acid sequence shown in SEQ ID NO;

12.

20. A pharmaceutical composition comprising (a) the antibody of claim 14, and (b) a pharmaceutically acceptable excipient.

21. A kit comprising the antibody of claim 14.