Antibodies directed against amyloid-beta peptide and nucleic acids encoding same

• US 7,763,250 B2
• Filed: 04/28/2006
• Issued: 07/27/2010
• 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): Kolker; Daniel E.
• Assistant Examiner(s): Emch; Gregory S
• Application Number:
  US11/413,817
• Publication Number:
  US 20060292152A1
• Time in Patent Office: 1,551 Days
• Field of Search: None
• US Class Current: 424/152.1
• 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

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

Claims

1. An isolated antibody comprising 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.

2. The antibody of claim 1, wherein the isotype of the antibody is selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.

3. The antibody of claim 1, wherein N-glycosylation in the Fc region is removed.

4. The antibody of claim 1, wherein the heavy chain constant region of the antibody is a human IgG2a constant region comprising amino acid mutations A330P331 to S330S331, wherein the amino acid position is based on Kabat numbering with reference to human wildtype IgG2a sequence.

5. The antibody of claim 1, 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.

6. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.

7. An isolated antibody comprising the heavy chain amino acid sequence of SEQ ID NO:

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

12.

8. An isolated antibody heavy chain comprising the three CDRs from antibody 6G heavy chain variable region comprising the amino acid sequences SEQ ID NO:

3, SEQ ID NO;

4, and SEQ ID NO;

5.

9. The antibody heavy chain of claim 8, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO:

1.

10. An isolated polynucleotide comprising a nucleotide sequence encoding the antibody heavy chain of claim 8.

11. A vector comprising the polynucleotide of claim 10.

12. The vector of claim 11, wherein the vector is pDb.6G.hFc2a with a deposit number of ATCC No. PTA-6786.

13. An isolated host cell comprising the polynucleotide of claim 10.

14. A method of producing an antibody, comprising culturing the host cell of claim 13 under conditions such that the antibody is produced;

and isolating the antibody from the host cell or culture.

15. An isolated antibody light chain comprising the three CDRs from antibody 6G light chain variable region comprising the amino acid sequences of SEQ ID NO:

6, SEQ ID NO. 7, and SEQ ID NO. 8.

16. The antibody light chain of claim 15, wherein the light chain comprises the amino acid sequence of SEQ ID NO:

2.

17. An isolated polynucleotide comprising a nucleotide sequence encoding the light chain of claim 15.

18. A vector comprising the polynucleotide of claim 17.

19. The vector of claim 18, wherein the vector is pEb.6G.hK with a deposit number of ATCC No. PTA-6787.

20. An isolated host cell comprising the polynucleotide of claim 17.

21. A fragment of antibody 6G, wherein the fragment has or retains the binding specificity of antibody 6G.

22. The fragment of claim 21, wherein the fragment is a Fab, a Fab′

, a F(ab′

)₂, or a Fv.

23. An isolated polynucleotide comprising a nucleotide sequence encoding the fragment of claim 21.

24. A vector comprising the polynucleotide of claim 23.

25. An isolated host cell comprising the polynucleotide of claim 23.

26. An isolated polynucleotide comprising a nucleotide sequence encoding the antibody light chain of SEQ ID NO. 2.

27. An isolated polynucleotide comprising a nucleotide sequence encoding the antibody heavy chain of SEQ ID NO:

1.

28. A vector comprising the polynucleotide of claim 27.

29. An isolated host cell comprising the polynucleotide of claim 27.