POLYNUCLEOTIDES ENCODING ANTIBODIES DIRECTED AGAINST AMYLOID-BETA PEPTIDE

• US 20110008834A1
• Filed: 04/05/2010
• Published: 01/13/2011
• Est. Priority Date: 07/30/2004
• Status: Active Grant

• Current Assignee: Rinat Neuroscience Corp. (Pfizer Inc.)
• Original Assignee: Rinat Neuroscience Corp. (Pfizer Inc.)
• Inventors: Rosenthal, Arnon, Pons, Jaume, Ho, Wei-Hsien, Grimm, Jan Markus
• Granted Patent: US 8,268,593 B2
• Time in Patent Office: Days
• US Class Current: 435/69.1
• 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. A polynucleotide encoding an antibody, said polynucleotide comprising at least one nucleic acid sequence selected from the group consisting of a nucleic acid sequence encoding a heavy chain variable region comprising CDRs comprising the amino acid sequences of SEQ ID NO:

3, SEQ ID NO;

4, and SEQ ID NO;

5, and a nucleic acid sequence encoding a light chain variable region comprising CDRs comprising the amino acid sequences of SEQ ID NO;

6, SEQ ID NO;

7, and SEQ ID NO;

8.

2. The polynucleotide of claim 1, comprising at least one nucleic acid sequence selected from the group consisting of a nucleic acid sequence encoding a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

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

2.

3. The polynucleotide of claim 2, comprising a nucleic acid sequence encoding a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

1.

4. The polynucleotide of claim 2, comprising a nucleic acid sequence encoding a light chain variable region comprising the amino acid sequence of SEQ ID NO:

2.

5. The polynucleotide of claim 2, comprising a nucleic acid sequence encoding a heavy chain variable region comprising the amino acid sequence of SEQ ID NO:

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

2.

6. The polynucleotide of claim 2, comprising at least one nucleic acid sequence selected from the group consisting of a nucleic acid sequence encoding a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:

11, and a nucleic acid sequence encoding a light chain polypeptide comprising the amino acid sequence of SEQ ID NO;

12.

7. The polynucleotide of claim 6, comprising a nucleic acid sequence encoding a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:

11, and a nucleic acid sequence encoding a light chain polypeptide comprising the amino acid sequence of SEQ ID NO;

12.

8. A vector comprising the polynucleotide of claim 3.

9. A vector comprising the polynucleotide of claim 4.

10. A vector comprising the polynucleotide of claim 5.

11. A vector comprising the polynucleotide of claim 6, wherein said polynucleotide comprises a nucleic acid sequence encoding a heavy chain polypeptide comprising the amino acid sequence of SEQ ID NO:

11.

12. A vector comprising the polynucleotide of claim 6, wherein said polynucleotide comprises a nucleic acid sequence encoding a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:

12.

13. A vector comprising the polynucleotide of claim 7.

14. A host cell comprising the vector of claim 11.

15. A host cell comprising the vector of claim 11, the cell further comprising a vector comprising polynucleotide comprising a nucleic acid sequence encoding a light chain polypeptide comprising the amino acid sequence of SEQ ID NO:

12.

16. A host cell comprising the vector of claim 13.

17. A method of producing the antibody of claim 1, said method comprising culturing the host cell of claim 15 under conditions where the antibody is expressed, and further comprising isolating the antibody from the cell or culture.

18. A method of producing the antibody of claim 1, said method comprising culturing the host cell of claim 16 under conditions where the antibody is expressed, and further comprising isolating the antibody from the cell or culture.

19. The method of claim 18, wherein said mammalian cell is selected from the group consisting of COS, HeLa, and CHO.

20. An isolated polynucleotide comprising the nucleic acid of the vector deposited under ATCC Accession No. PTA-6124 that encodes a heavy chain variable region of an antibody.

22. The isolated polynucleotide of claim 20, wherein said nucleic acid sequence encodes a heavy chain polypeptide as comprised in the vector deposited under ATCC Accession No. PTA-6124.

21. An isolated polynucleotide comprising the nucleic acid of the vector deposited under ATCC Accession No. PTA-6125 that encodes a light chain variable region of an antibody.

23. The isolated polynucleotide of claim 21, wherein said nucleic acid sequence encodes a light chain polypeptide as comprised in the vector deposited under ATCC Accession No. PTA-6125.

24. An isolated polynucleotide comprising the nucleic acid sequence set forth in SEQ ID NO:

9.

26. The isolated polynucleotide of claim 24, said polynucleotide comprising the nucleic acid sequence set forth in SEQ ID NO:

13.

28. A vector comprising the isolated polynucleotide of claim 26.

30. The vector of claim 26, said vector further comprising the nucleic acid sequence of SEQ ID NO:

14.

31. A host cell comprising vector of claim 28 and further comprising a vector comprising a polynucleotide comprising the nucleic acid sequence seth forth in SEQ ID NO:

14.

32. A host cell comprising the vector of claim 30.

33. A method of producing an antibody that specifically binds an Aβ

peptide, comprising culturing the host cell of claim 32 under conditions allowing expression of the polynucleotide encoding the heavy chain polypeptide and the light chain polypeptide thereby producing the antibody.

34. The method of claim 33, wherein said host cell is a mammalian cell selected from the group consisting of COS, HeLa and CHO.

25. An isolated polynucleotide comprising the nucleic acid sequence set forth in SEQ ID NO:

10.

27. The isolated polynucleotide of claim 25, said polynucleotide comprising the nucleic acid sequence set forth in SEQ ID NO:

14.

29. A vector comprising the isolated polynucleotide of claim 27.

35. An isolated polynucleotide encoding an antibody heavy chain polypeptide said polynucleotide comprising the nucleic acid sequence encoding the heavy chain polypeptide as comprised in vector pDb.9TL.hFc2a deposited as ATCC No. PTA-6124.

37. A method of producing an antibody, said method comprising introducing said polynucleotide encoding said heavy chain of claim 35 into a host cell, introducing a polynucleotide encoding a light chain wherein said polynucleotide comprises the nucleic acid sequence encoding said light chain of vector pEb.9TL.hK deposited as ATCC No. PTA-6125 into said cell, culturing said cell under conditions where the polynucleotides are expressed and isolating the antibody from said cell or culture, thereby producing said antibody.

36. An isolated polynucleotide encoding an antibody light chain polypeptide said polynucleotide comprising the nucleic acid sequence encoding the light chain as comprised in vector pEb.9TL.hK deposited as ATCC No. PTA-6125.