Anti-ABeta Globulomer Antibodies, Antigen-Binding Moieties Thereof, Corresponding Hybridomas, Nucleic Acids, Vectors, Host Cells, Methods of Producing Said Antibodies, Compositions Comprising Said Antibodies, Uses Of Said Antibodies And Methods Of Using Said Antibodies

• US 20090191190A1
• Filed: 11/30/2006
• Published: 07/30/2009
• Est. Priority Date: 11/30/2005
• Status: Active Grant

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Inventors: Keller, Patrick, Labkovsky, Boris, Barghorn, Stefan, Hillen, Heinz, Striebinger, Andreas R., Ebert, Ulrich
• Granted Patent: US 8,691,224 B2
• Time in Patent Office: Days
• US Class Current: 424/133.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07K 14/4711 Alzheimer's disease; Amyloid plaque core protein
• 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 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: G01N 2333/4709 Amyloid plaque core protein
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 2800/387 Down syndrome; Trisomy 18; Trisomy 13
• CPC Class Codes: G01N 33/6896 Neurological disorders, e.g. Alzheimer's disease

Abstract

Anti-Aβ globulomer antibodies, antigen-binding moieties thereof, corresponding hybridomas, nucleic acids, vectors, host cells, methods of producing said antibodies, compositions comprising said antibodies, uses of said antibodies and methods of using said antibodies.

The present invention relates to anti-Aβ globulomer antibodies having a binding affinity to Aβ(20-42) globulomer that is greater than the binding affinity of the antibody to Aβ(1-42) globulomer, antigen-binding moieties thereof, hybridomas producing said antibodies, nucleic acids encoding said antibodies, vectors comprising said nucleic acids, host cells comprising said vectors, methods of producing said antibodies, compositions comprising said antibodies, therapeutic and diagnostic uses of said antibodies and corresponding methods relating to Alzheimer'"'"'s disease and other amyloidoses.

Claims

1. :

An antibody selected from the group consisting of an isolated antibody, a monoclonal antibody and a recombinant antibody, wherein said antibody has a binding affinity to an Aβ

(20-42) globulomer that is greater than the binding affinity of the antibody to an Aβ

(1-42) globulomer.

2. :

The antibody of claim 1, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 10 times greater than the binding affinity of the antibody to the Aβ

(1-42) globulomer.

3. :

The antibody of claim 2 wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 100 times greater than the binding affinity of the antibody to the Aβ

(1-42) globulomer.

4. :

The antibody of claim 3, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 1000 times greater than the binding affinity of the antibody to the Aβ

(1-42) globulomer.

5. :

The antibody of claim 4, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 10000 times greater than the binding affinity of the antibody to the Aβ

(1-42) globulomer.

6. :

The antibody of claim 5, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 100000 times greater than the binding affinity of the antibody to the Aβ

(1-42) globulomer.

7. :

The antibody of claim 1, wherein the antibody binds to the Aβ

(20-42) globulomer with a K_D in the range of 1×

10<sup>−

6</sup> M to 1×

10<sup>−

12</sup> M.

8. :

The antibody of claim 7, wherein the antibody binds to the Aβ

(20-42) globulomer with a K_D of 1×

10<sup>−

7</sup> M or greater affinity.

9. :

The antibody of claim 8, wherein the antibody binds to the Aβ

(20-42) globulomer with a K_D of 1×

10<sup>−

8</sup> M or greater affinity.

10. :

The antibody of claim 9, wherein the antibody binds to the Aβ

(20-42) globulomer with a K_D of 1×

10<sup>−

9</sup> M or greater affinity.

11. The antibody of claim 10, wherein the antibody binds to the Aβ

(20-42) globulomer with a K_D of 1×

10<sup>−

10</sup> M or greater affinity.

12. :

The antibody of claim 11, wherein the antibody binds to the Aβ

(20-42) globulomer with a K_D of 1×

10¹¹ M or greater affinity.

13. :

The antibody of claim 1, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is greater than the binding affinity of the antibody to an Aβ

(12-42) globulomer.

14. :

The antibody of claim 13, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 10 times greater than the binding affinity of the antibody to the Aβ

(12-42) globulomer.

15. :

The antibody of claim 14, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 100 times greater than the binding affinity of the antibody to the Aβ

(12-42) globulomer.

16. :

The antibody of claim 15, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 1000 times greater than the binding affinity of the antibody to the Aβ

(2-42) globulomer.

17. :

The antibody of claim 16, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 10000 times greater than the binding affinity of the antibody to the Aβ

(12-42) globulomer.

18. :

The antibody of claim 17, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 100000 times greater than the binding affinity of the antibody to the Aβ

(12-42) globulomer.

19. :

The antibody of claim 7, wherein the antibody binds to the Aβ

(20-42) globulomer with a K_D in the range of 1×

10<sup>−

6</sup> M to 1×

10<sup>−

12</sup> M, to the Aβ

(1-42) globulomer with a K_D Of 10<sup>−

12</sup> M or smaller affinity, the binding affinity to the Aβ

(20-42) globulomer being greater than the binding affinity to the Aβ

(1-42) globulomer.

20. :

The antibody of claim 19, wherein the antibody binds to the Aβ

(12-42) globulomer with a K_D of 10<sup>−

12</sup> M or smaller affinity, the binding affinity to the Aβ

(20-42) globulomer being greater than the binding affinity to the Aβ

(12-42) globulomer.

21. :

The antibody of claim 1, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 10 times greater than to an Aβ

(1-42) monomer.

22. :

The antibody of claim 21, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 100 times greater than to the Aβ

(1-42) monomer.

23. :

The antibody of claim 22, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 1000 times greater than to the Aβ

(1-42) monomer.

24. The antibody of claim 23, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 10000 times greater than to the Aβ

(1-42) monomer.

25. :

The antibody of claim 24, wherein the binding affinity of the antibody to Aβ

(20-42) globulomer is at least 100000 times greater than to the Aβ

(1-42) monomer.

26. :

The antibody of claim 1, wherein the antibody binds to the an Aβ

(1-42) monomer with a K_D of 1×

10<sup>−

8</sup> M or smaller affinity.

27. :

The antibody of claim 26, wherein the antibody binds to the Aβ

(1-42) monomer with a K_D of 1×

10<sup>−

7</sup> M or smaller affinity.

28. :

The antibody of claim 27, wherein the antibody binds to the Aβ

(1-42) monomer with a K_D of 1×

10<sup>−

6</sup> M or smaller affinity.

29. :

The antibody of claim 28, wherein the antibody binds to the Aβ

(1-42) monomer with a K_D of 1×

10<sup>−

5</sup> M or smaller affinity.

30. :

The antibody of claim 1, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 10 times greater than the binding affinity of the antibody to an Aβ

(1-40) monomer.

31. :

The antibody of claim 30, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 100 times greater than the binding affinity of the antibody to the Aβ

(1-40) monomer.

32. :

The antibody of claim 31, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 1000 times greater than the binding affinity of the antibody to the Aβ

(1-40) monomer.

33. :

The antibody of claim 32, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 10000 times greater than the binding affinity of the antibody to the Aβ

(1-40) monomer.

34. :

The antibody of claim 33, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 100000 times greater than the binding affinity of the antibody to the Aβ

(1-40) monomer.

35. :

The antibody of claim 1, wherein the antibody binds to an Aβ

(1-40) monomer with a K_D of 1×

10<sup>−

8</sup> M or smaller affinity.

36. :

The antibody of claim 35, wherein the antibody binds to the Aβ

(1-40) monomer with a K_D of 1×

10<sup>−

7</sup> M or smaller affinity.

37. :

The antibody of claim 36, wherein the antibody binds to the Aβ

(1-40) monomer with a K_D of 1×

10<sup>−

6</sup> M or smaller affinity.

38. :

The antibody of claim 37, wherein the antibody binds to the Aβ

(1-40) monomer with a K_D of 1×

10<sup>−

5</sup> or smaller affinity.

39. :

The antibody of claim 1, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 10 times greater than the binding affinity of the antibody to Aβ

(1-42) fibrils.

40. :

The antibody of claim 39, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 100 times greater than the binding affinity of the antibody to Aβ

(1-42) fibrils.

41. :

The antibody of claim 40, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 1000 times greater than the binding affinity of the antibody to Aβ

(1-42) fibrils.

42. :

The antibody of claim 41, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 10000 times greater than the binding affinity of the antibody to Aβ

(1-42) fibrils.

43. :

The antibody of claim 42, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 100000 times greater than the binding affinity of the antibody to Aβ

(11-42) fibrils.

44. :

The antibody of claim 39, wherein the antibody binds to A3(1-42) fibrils with a KID of 1×

10<sup>−

8</sup> M or smaller affinity.

45. :

The antibody of claim 44, wherein the antibody binds to Aβ

(1-42) fibrils with a K_D of 1×

10<sup>−

7</sup> M or smaller affinity.

46. :

The antibody of claim 45, wherein the antibody binds to Aβ

(1-42) fibrils with a K_D of 1×

10<sup>−

6</sup> M or smaller affinity.

47. :

The antibody of claim 46, wherein the antibody binds to Aβ

(1-42) fibrils with a K_D of 1×

10<sup>−

5</sup> M or smaller affinity.

48. :

The antibody of claim 1, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 10 times greater than the binding affinity of the antibody to Aβ

(1-40) fibrils.

49. :

The antibody of claim 48, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 100 times greater than the binding affinity of the antibody to Aβ

(1-40) fibrils.

50. :

The antibody of claim 49, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 1000 times greater than the binding affinity of the antibody to Aβ

(1-40) fibrils.

51. :

The antibody of claim 50, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 10000 times greater than the binding affinity of the antibody to Aβ

(1-40) fibrils.

52. :

The antibody of claim 51, wherein the binding affinity of the antibody to the Aβ

(20-42) globulomer is at least 100000 times greater than the binding affinity of the antibody to Aβ

(1-40) fibrils.

53. :

The antibody of claim 1, wherein the antibody binds to Aβ

(1-40) fibrils with a K_D of 1×

10<sup>−

8</sup> M or smaller affinity.

54. :

The antibody of claim 53, wherein the antibody binds to Aβ

(1-40) fibrils with a K_D of 1×

10<sup>−

7</sup> M or smaller affinity.

55. :

The antibody of claim 54, wherein the antibody binds to Aβ

(1-40) fibrils with a K_D of 1×

10<sup>−

6</sup> M or smaller affinity.

56. :

The antibody of claim 55, wherein the antibody binds to Aβ

(1-40) fibrils with a K_D of 1×

10<sup>−

5</sup> or smaller affinity.

60. :

The antibody of claim 1, wherein the antibody is human or humanized.

61. :

The antibody of claim 60, wherein said antibody binds to the same epitope as a monoclonal antibody selected from the group consisting of the monoclonal antibody 5F7 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7241, the monoclonal antibody 10F11 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7239, the monoclonal antibody 7C6 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7240, the monoclonal antibody 4B7 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7242, the monoclonal antibody 2F2 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7408, the monoclonal antibody 6A2 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7409, the monoclonal antibody 4D10 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7405, the monoclonal antibody 7E5 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7809, the monoclonal antibody 10C1 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7810, and the monoclonal antibody 3B 10 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7851.

62. :

The antibody of claim 61, wherein the antibody comprises at least one amino acid sequence selected from the group consisting of the amino acid sequence of the heavy chain CDR3 and the amino acid sequence of the light chain CDR3 of a monoclonal antibody selected from the group consisting of the monoclonal antibody 5F7 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7241, the monoclonal antibody 10F11 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7239, the monoclonal antibody 7C6 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7240, the monoclonal antibody 4B7 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7242, the monoclonal antibody 2F2 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7408, the monoclonal antibody 6A2 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7409, the monoclonal antibody 4D10 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7405, the monoclonal antibody 7E5 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7809, the monoclonal antibody 10C1 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7810, and the monoclonal antibody 3B10 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7851.

63. :

The antibody of claim 62, wherein the antibody comprises at least one amino acid sequence selected from the group consisting of the amino acid sequence of the heavy chain CDR2 and the amino acid sequence of the light chain CDR2 of a monoclonal antibody selected from the group consisting of the monoclonal antibody 5F7 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7241, the monoclonal antibody 10F11 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7239, the monoclonal antibody 7C6 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7240, the monoclonal antibody 4B7 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7242, the monoclonal antibody 2F2 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7408, the monoclonal antibody 6A2 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7409, the monoclonal antibody 4D 10 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7405, the monoclonal antibody 7E5 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7809, the monoclonal antibody 10C1 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7810, and the monoclonal antibody 3B10 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7851.

64. :

The antibody of claim 62 or claim 63, wherein the antibody comprises at least one amino acid sequence selected from the group consisting of the amino acid sequence of the heavy chain CDR1 and the amino acid sequence of the light chain CDR1 of a monoclonal antibody selected from the group consisting of the monoclonal antibody 5F7 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7241, the monoclonal antibody 10F11 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7239, the monoclonal antibody 7C6 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7240, the monoclonal antibody 4B7 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7242, the monoclonal antibody 2F2 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7408, the monoclonal antibody 6A2 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7409, the monoclonal antibody 4D10 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7405, the monoclonal antibody 7E5 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7809, the monoclonal antibody 10C1 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7810, and the monoclonal antibody 3B10 obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7851.

65. :

The antibody of claim 1 wherein the antibody comprises at least one CDR comprising an amino acid sequence selected from the group consisting of;

amino acid residues 31-35 of SEQ ID NO;

3, amino acid residues 50-66 of SEQ ID NO;

3, amino acid residues 99-109 of SEQ ID NO;

3, amino acid residues 24-39 of SEQ ID NO;

4, amino acid residues 55-61 of SEQ ID NO;

4, amino acid residues 94-102 of SEQ ID NO;

4, amino acid residues 31-35 of SEQ ID NO;

7, amino acid residues 50-66 of SEQ ID NO;

7, amino acid residues 97-109 of SEQ ID NO;

7, amino acid residues 24-39 of SEQ ID NO;

8, amino acid residues 55-61 of SEQ ID NO;

8, amino acid residues 94-102 of SEQ ID NO;

8, amino acid residues 31-35 of SEQ ID NO;

11, amino acid residues 50-65 of SEQ ID NO;

11, amino acid residues 98-107 of SEQ ID NO;

11, amino acid residues 24-39 of SEQ ID NO;

12, amino acid residues 55-61 of SEQ ID NO;

12, amino acid residues 94-102 of SEQ ID NO 12, amino acid residues 31-35 of SEQ ID NO;

15, amino acid residues 50-66 of SEQ ID NO;

15, amino acid residues 99-107 of SEQ ID NO;

15, amino acid residues 24-40 of SEQ ID NO 16, amino acid residues 56-62 of SEQ ID NO;

16, amino acid residues 95-103 of SEQ ID NO;

16, amino acid residues 31-35 of SEQ ID NO;

19, amino acid residues 50-66 of SEQ ID NO;

19, amino acid residues 99-109 of SEQ ID NO;

19, amino acid residues 24-39 of SEQ ID NO;

20, amino acid residues 55-61 of SEQ ID NO;

20, amino acid residues 94-102 of SEQ ID NO;

20, amino acid residues 31-35 of SEQ ID NO;

23, amino acid residues 50-66 of SEQ ID NO;

23, amino acid residues 99-109 of SEQ ID NO;

23, amino acid residues 24-39 of SEQ ID NO;

24, amino acid residues 55-61 of SEQ ID NO;

24, amino acid residues 94-102 of SEQ ID NO;

24, amino acid residues 31-35 of SEQ ID NO;

27, amino acid residues 50-65 of SEQ ID NO;

27, amino acid residues 98-101 of SEQ ID NO;

27, amino acid residues 24-39 of SEQ ID NO;

28, amino acid residues 55-61 of SEQ ID NO;

28, amino acid residues 94-102 of SEQ ID NO;

28, amino acid residues 31-35 of SEQ ID NO;

31, amino acid residues 50-66 of SEQ ID NO;

31, amino acid residues 99-107 of SEQ ID NO;

31, amino acid residues 24-40 of SEQ ID NO;

32, amino acid residues 56-62 of SEQ ID NO;

32, amino acid residues 95-103 of SEQ ID NO;

32, amino acid residues 31-35 of SEQ ID NO;

35, amino acid residues 50-66 of SEQ ID NO;

35, amino acid residues 99-107 of SEQ ID NO;

35, amino acid residues 24-40 of SEQ ID NO;

36, amino acid residues 56-62 of SEQ ID NO;

36, amino acid residues 95-103 of SEQ ID NO;

36, amino acid residues 31-35 of SEQ ID NO;

38, amino acid residues 50-66 of SEQ ID NO;

38, and amino acid residues 98-109 of SEQ ID NO;

38.

66. :

The antibody of claim 65 wherein the antibody comprises at least 3 CDRs.

67. :

The antibody of claim 66 wherein the at least 3 CDRs are selected from a variable domain CDR set consisting of;

68. :

The antibody of claim 67 wherein the antibody comprises at least 2 variable domain CDR sets.

69. The antibody of claim 68 wherein the at least 2 variable domain CDR sets are selected from the group consisting of:

VH 5F7 CDR Set &

VL 5F7 CDR Set;

VH 10F11 CDR Set &

VL 10F11 CDR Set;

VH 7C6 CDR Set &

VL, 7C6 CDR Set;

VH 4B7 CDR Set &

VL 4B7 CDR Set;

VH 2F2 CDR Set &

VL 2F2 CDR Set;

VH 6A2 CDR Set &

VL 6A2 CDR Set;

VH 4D10 CDR Set &

VL 4D10 CDR Set;

VH 7E5 CDR Set &

VL 7E5 CDR Set; and

VH 10C1 CDR Set &

VL 10C1 CDR Set.

88. :

Antigen-binding moiety of an antibody of claim 1.

89. :

The antigen-binding moiety of claim 88, wherein tie moiety is selected from the group consisting of a Fab fragment, a F(ab′

)₂ fragment and a single chain Fv fragment of the antibody.

91. :

An isolated nucleic acid encoding the amino acid sequence of the antibody of claim 1.

92. :

Vector comprising said isolated nucleic acid of claim 91.

93. :

The vector of claim 92 wherein said vector is selected from the group consisting of pcDNA, pTT, pTT3, pEFBOS, pBV, pJV, and pBJ.

94. :

An isolated host cell comprising said vector of claim 92 or claim 93.

95. :

The host cell of claim 94 wherein said host cell is a prokaryotic cell.

96. :

The host cell of claim 95 wherein said prokaryotic cell is Escherichia coli.

97. :

The host cell of claim 94 wherein said host cell is an eukaryotic cell.

98. :

The host cell of claim 97 wherein said eukaryotic cell is selected from the group consisting of a protist cell, an animal cell, a plant cell and a fungal cell.

99. :

The host cell of claim 98 wherein said animal cell is selected from the group consisting of a mammalian cell, an avian cell, and an insect cell.

100. :

The host cell of claim 97 wherein said eukaryotic cell is selected from a group consisting of a CHO cell, a COS cell and a yeast cell.

101. :

The host cell of claim 100 wherein said yeast cell is Saccharomyces cerevisiae.

102. :

The host cell of claim 99 wherein said insect cell is an insect Sf9 cell.

105. :

Composition comprising said antibody of claim 1 or said antigen-binding moiety of claim 88.

106. :

The composition of claim 105, wherein said composition is a pharmaceutical composition and further comprises a pharmaceutical acceptable carrier.

107. :

A method for treating or preventing an amyloidosis in a patient comprising the step of administering said antibody of claim 1 or said antigen-binding moiety of claim 88 to a patient in an amount sufficient to effect said treatment or prevention.

108. :

The method of claim 107, wherein said antibody or said antigen-binding moiety is for passive immunization.

110. :

The method of claim 107 or claim 109 wherein the amyloidosis is Alzheimer'"'"'s disease.

111. :

The method of claim 107 or claim 109 wherein the amyloidosis is the amyloidosis of Down'"'"'s syndrome.

57. (canceled)

58. (canceled)

59. (canceled)

70. :

An antibody selected from the group consisting of an isolated antibody, a monoclonal antibody and a recombinant antibody, wherein said antibody comprises at least one variable domain having an amino acid sequence selected from the group consisting of;

SEQ ID NO;

3, SEQ ID NO;

4, SEQ ID NO;

7, SEQ ID NO;

8, SEQ ID NO;

11, SEQ ID NO;

12, SEQ ID NO;

15, SEQ ID NO;

16, SEQ ID NO;

19, SEQ ID NO;

20, SEQ ID NO;

23, SEQ ID NO;

24, SEQ ID NO;

27, SEQ ID NO;

28, SEQ ID NO;

31, SEQ ID NO;

32, SEQ ID NO;

35, SEQ ID NO;

36, and SEQ ID NO;

38.

71. :

The antibody of claim 70 comprising two variable domains, wherein said two variable domains have amino acid sequences selected from the group consisting oft SEQ ID NO;

3 &

SEQ ID NO;

4, SEQ ID NO;

7 &

SEQ ID NO;

8 &

SEQ ID NO;

11 &

SEQ ID NO;

12, SEQ ID NO;

15 &

SEQ ID NO;

16, SEQ ID NO;

19 &

SEQ ID NO;

20, SEQ ID NO;

23 &

SEQ ID NO;

24, SEQ ID NO;

27 &

SEQ ID NO;

28, SEQ ID NO;

31 &

SEQ ID NO;

32, and SEQ ID NO;

35 &

SEQ ID NO;

36.

72. :

The antibody of claim 70 of claim 71 wherein the antibody comprises a constant region.

73. :

The antibody of claim 72, wherein the antibody comprises a heavy chain constant region selected from the group consisting of IgG1, IgG2, IgG3, IgG34, IgM, IgA, IgD and IgE constant regions.

74. :

The antibody of claim 73, wherein the antibody comprises an IgG1 heavy chain constant region.

75. :

The antibody of claim 73, wherein the constant region is a human constant region.

76. :

The antibody of claim 72, wherein the constant region comprises an amino acid sequence selected from the group consisting of SEQ ID NO;

39. SEQ ID NO;

40, SEQ ID NO;

41 aid SEQ ID NO;

42.

77. :

The antibody of claim 76, wherein the antibody possesses a human glycosylation pattern.

78. :

Monoclonal antibody (5F7) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7241.

79. :

Monoclonal antibody (10F11) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7239.

80. :

Monoclonal antibody (7C6) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7240.

81. :

Monoclonal antibody (4B7) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7242.

82. :

Monoclonal antibody (2F2) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7408.

83. :

Monoclonal antibody (6A2) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7409.

84. :

Monoclonal antibody (4D10) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7405.

85. :

Monoclonal antibody (7E5) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7809.

86. :

Monoclonal antibody (10C1) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7810.

87. :

Monoclonal antibody (3B10) obtainable from a hybridoma designated by American Type Culture Collection deposit number PTA-7851.

90. :

Hybridoma designated by an American Type Culture Collection deposit number selected from the group consisting of PTA-7241, PTA-7239, PTA-7240, PTA-7242, PTA-7408, PTA-7409, PTA-7405, PTA-7809, PTA-7810 and PTA-7851.

103. :

Method of producing an antibody, comprising culturing said host cell of claim 94 or said hybridoma of claim 90 in culture medium under conditions suitable to produce the antibody.

104. :

An antibody obtainable by said method of claim 103.

109. :

A method of diagnosing an amyloidosis in a patient suspecting of having this condition comprising the steps of;

a) isolating a biological sample from said patient; and

b) contacting said antibody or antigen-binding moiety with said biological sample for a time and under conditions sufficient to form antibody/antigen or antigen-binding moiety/antigen complexes, presence of either complex indicating said patient has said amyloidosis.

112. (canceled)

113. (canceled)

114. (canceled)

115. (canceled)

116. (canceled)