MONOCLONAL ANTIBODY

• US 20100291097A1
• Filed: 10/03/2008
• Published: 11/18/2010
• Est. Priority Date: 10/05/2007
• Status: Active Grant

• Current Assignee: AC Immune SA, Genentech, Inc. (Roche Holding AG)
• Original Assignee: AC Immune SA
• Inventors: Pfeifer, Andrea, Pihlgren, Maria, Muhs, Andreas, Watts, Ryan
• Granted Patent: US 9,403,902 B2
• Time in Patent Office: Days
• US Class Current: 424/141.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 27/00 Drugs for disorders of the senses
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/06 Antiglaucoma agents or miotics
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/56 variable (Fv) region, i.e. VH and/or VL
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]

Abstract

The present invention provides novel methods and compositions comprising highly specific and highly effective antibodies that specifically recognize and bind to specific epitopes from a range of β-amyloid proteins. The antibodies of the present invention are particularly useful for the treatment of ocular diseases associated with pathological abnormalities/changes in the tissues of the visual system, particularly those ocular diseases associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system.

Claims

1. A pharmaceutical composition for the treatment of an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, comprising a therapeutically effective amount of the monoclonal antibody ACI-24-Ab-3.

2. The pharmaceutical composition of claim 1, wherein the ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, is selected from the group consisting of cortical visual deficits, glaucoma, primary retinal degeneration, including macular degeneration, optic nerve drusen, optic neuropathy, optic neuritis, cataract, ocular amyloidosis and lattice dystrophy.

3. The pharmaceutical composition of claim 2, wherein the ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, is glaucoma.

4. The pharmaceutical composition of claim 3, wherein the glaucoma is selected from the group consisting of chronic open-angle glaucoma (COAG), acute angle closure glaucoma (AACG), mixed or combined mechanism glaucoma, normal tension glaucoma, congenital glaucoma, secondary glaucoma, pigmentary glaucoma and exfoliative glaucoma.

5. A method for reducing the plaque load in the retinal ganglion cell layer of a subject suffering from an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, comprising administering to the animal the pharmaceutical composition of claim 1.

6. The method of claim 5, wherein the subject is a mammal.

7. The method of claim 6, wherein the mammal is a human.

8. A method for reducing the amount of plaques in the retinal ganglion cell layer of a subject suffering from an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, comprising administering to the animal the pharmaceutical composition of claim 1.

9. The method of claim 8, wherein the subject is a mammal.

10. The method of claim 9, wherein the mammal is a human.

11. A method for decreasing the total amount of soluble amyloid-β

in the retinal ganglion cell layer of a subject comprising administering to the animal the pharmaceutical composition of claim 1.

12. The method of claim 11, wherein the subject is a mammal.

13. The method of claim 12, wherein the mammal is a human.

14. A method for preventing, treating or alleviating the effects of an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, in a subject comprising administering to the animal the pharmaceutical composition of claim 1.

15. The method of claim 14, wherein the subject is a mammal.

16. The method of claim 15, wherein the mammal is a human.

23. A method for monitoring minimal residual ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, in a subject following treatment with the pharmaceutical composition of claim 1, wherein said method comprises:

(a) bringing a sample or a specific body part or body area suspected to contain the amyloid protein into contact with the monoclonal antibody ACI-24-Ab-3, a functionally equivalent antibody thereof or functional parts thereof, which monoclonal antibody binds an epitope of the amyloid protein;

(b) allowing the monoclonal antibody to bind to the amyloid protein to form an immunological complex;

(c) detecting the formation of the immunological complex;

(d) correlating the presence or absence of the immunological complex with the presence or absence of amyloid protein in the sample or specific body part or area; and

(e) comparing the amount of said immunological complex to a normal control value,

wherein an increase in the amount of said complex compared to a normal control value indicates that the subject still suffers from a minimal residual ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system.

24. The method of claim 23, wherein the subject is a mammal.

25. The method of claim 24, wherein the mammal is a human.

26. A method for predicting responsiveness of a subject being treated with the pharmaceutical composition of claim 1 comprising the steps of:

(a) bringing a sample or a specific body part or body area suspected to contain an amyloid protein into contact with the monoclonal antibody ACI-24-Ab-3, a functionally equivalent antibody thereof or functional parts thereof, which monoclonal antibody binds an epitope of the amyloid protein;

(b) allowing the monoclonal antibody to bind to the amyloid protein to form an immunological complex;

(c) detecting the formation of the immunological complex;

(d) correlating the presence or absence of the immunological complex with the presence or absence of amyloid protein in the sample or specific body part or area; and

(e) comparing the amount of said immunological complex before and after onset of the treatment,

wherein a decrease in the amount of said immunological complex indicates that the subject has a high potential of being responsive to the treatment.

27. The method of claim 26, wherein the subject is a mammal.

28. The method of claim 27, wherein the mammal is a human.

29. A method for retaining or decreasing ocular pressure in the eyes of a subject suffering from an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 1.

30. The method of claim 29, wherein the subject is a mammal.

31. The method of claim 30, wherein the mammal is a human.

57. A method for predicting responsiveness of a subject being treated with the pharmaceutical composition of claim 1 comprising the steps of:

(a) bringing a sample or a specific body part or body area suspected to contain an amyloid protein into contact with a monoclonal antibody selected from the group consisting of ACI-11-Ab-9, ACI-12-Ab-11, functionally equivalent antibodies thereof and functional parts thereof, which monoclonal antibody binds an epitope of the amyloid protein;

(b) allowing the monoclonal antibody to bind to the amyloid protein to form an immunological complex;

(c) detecting the formation of the immunological complex;

(d) correlating the presence or absence of the immunological complex with the presence or absence of amyloid protein in the sample or specific body part or area; and

(e) comparing the amount of said immunological complex before and after onset of the treatment,

wherein a decrease in the amount of said immunological complex indicates that the subject has a high potential of being responsive to the treatment.

58. The method of claim 57, wherein the subject is a mammal.

59. The method of claim 58, wherein the mammal is a human.

17. A method for diagnosing an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, in a subject comprising detecting the immunospecific binding of the monoclonal antibody ACI-24-Ab-3, a functionally equivalent antibody thereof or functional parts thereof, to an epitope of the amyloid protein in a sample or in situ which includes the steps of

(a) bringing the sample or a specific body part or body area suspected to contain the amyloid protein into contact with an antibody according to the invention, which antibody binds an epitope of the amyloid protein;

(b) allowing the antibody to bind to the amyloid protein to form an immunological complex;

(c) detecting the formation of the immunological complex, particularly such that presence or absence of the immunological complex correlates with presence or absence of amyloid protein; and

(d) correlating the presence or absence of the immunological complex with the presence or absence of amyloid protein in the sample or specific body part or area.

18. The method of claim 17, wherein the subject is a mammal.

19. The method of claim 18, wherein the mammal is a human.

20. A method for diagnosing a predisposition to an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, in a subject comprising detecting the specific binding of the monoclonal antibody ACI-24-Ab-3, a functionally equivalent antibody thereof or functional parts thereof, to an epitope of the amyloid protein in a sample or in situ which includes the steps of

(a) bringing the sample or a specific body part or body area suspected to contain the amyloid protein into contact with the antibody, wherein the antibody binds a conformational epitope of the amyloid protein;

(b) allowing the antibody to bind to any amyloid protein in the sample to form an immunological complex;

(c) detecting the formation of the immunological complex;

(d) correlating the presence or absence of the immunological complex with the presence or absence of amyloid protein in the sample or specific body part or area; and

(e) comparing the amount of said immunological complex to a normal control value,

wherein an increase in the amount of said complex compared to a normal control value indicates that the subject is suffering from or is at risk of developing an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system.

21. The method of claim 20, wherein the subject is a mammal.

22. The method of claim 21, wherein the mammal is a human.

32. A pharmaceutical composition for the treatment of an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, comprising a therapeutically effective amount of a monoclonal antibody selected from the group consisting of ACI-11-Ab-9 and ACI-12-Ab-11.

33. The pharmaceutical composition of claim 32, wherein the ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, is selected from the group consisting of cortical visual deficits, glaucoma, primary retinal degeneration, including macular degeneration, optic nerve drusen, optic neuropathy, optic neuritis, cataract, ocular amyloidosis and lattice dystrophy.

34. The pharmaceutical composition of claim 33, wherein the ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, is glaucoma.

35. The pharmaceutical composition of claim 34, wherein the glaucoma is selected from the group consisting of chronic open-angle glaucoma (COAG), acute angle closure glaucoma (AACG), mixed or combined mechanism glaucoma, normal tension glaucoma, congenital glaucoma, secondary glaucoma, pigmentary glaucoma and exfoliative glaucoma.

36. A method for reducing the plaque load in the retinal ganglion cell layer of a subject suffering from an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, comprising administering to the subject the pharmaceutical composition of claim 32.

37. The method of claim 36, wherein the subject is a mammal.

38. The method of claim 37, wherein the mammal is a human.

39. A method for reducing the amount of plaques in the retinal ganglion cell layer of a subject suffering from an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, comprising administering to the subject the pharmaceutical composition of claim 32.

40. The method of claim 39, wherein the subject is a mammal.

41. The method of claim 40, wherein the mammal is a human.

42. A method for decreasing the total amount of soluble amyloid-β

in the retinal ganglion cell layer of a subject comprising administering to the animal the pharmaceutical composition of claim 32.

43. The method of claim 42, wherein the subject is a mammal.

44. The method of claim 43, wherein the mammal is a human.

45. A method for preventing, treating or alleviating the effects of an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, in a subject comprising administering to the animal the pharmaceutical composition of claim 32.

46. The method of claim 45, wherein the subject is a mammal.

47. The method of claim 46, wherein the mammal is a human.

54. A method for monitoring minimal residual ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, in a subject following treatment with the pharmaceutical composition of claim 32, wherein said method comprises:

(a) bringing a sample or a specific body part or body area suspected to contain the amyloid protein into contact with a monoclonal antibody selected from the group consisting of ACI-11-Ab-9, ACI-12-Ab-11, functionally equivalent antibodies thereof and functional parts thereof, which monoclonal antibody binds an epitope of the amyloid protein;

(b) allowing the monoclonal antibody to bind to the amyloid protein to form an immunological complex;

(c) detecting the formation of the immunological complex;

(d) correlating the presence or absence of the immunological complex with the presence or absence of amyloid protein in the sample or specific body part or area; and

(e) comparing the amount of said immunological complex to a normal control value,

wherein an increase in the amount of said complex compared to a normal control value indicates that the subject still suffers from a minimal residual ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system.

55. The method of claim 54, wherein the subject is a mammal.

56. The method of claim 55, wherein the mammal is a human.

60. A method for retaining or decreasing ocular pressure in the eyes of a subject suffering from an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of claim 32.

61. The method of claim 60, wherein the subject is a mammal.

62. The method of claim 61, wherein the mammal is a human.

48. A method for diagnosing an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, in a subject comprising detecting the immunospecific binding of a monoclonal antibody selected from the group consisting of ACI-11-Ab-9, ACI-12-Ab-11, functionally equivalent antibodies thereof and functional parts thereof, to an epitope of the amyloid protein in a sample or in situ which includes the steps of

(a) bringing the sample or a specific body part or body area suspected to contain the amyloid protein into contact with an antibody according to the invention, which antibody binds an epitope of the amyloid protein;

(b) allowing the antibody to bind to the amyloid protein to form an immunological complex;

(c) detecting the formation of the immunological complex, particularly such that presence or absence of the immunological complex correlates with presence or absence of amyloid protein; and

(d) correlating the presence or absence of the immunological complex with the presence or absence of amyloid protein in the sample or specific body part or area.

49. The method of claim 48, wherein the subject is a mammal.

50. The method of claim 49, wherein the mammal is a human.

51. A method for diagnosing a predisposition to an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system, such as neuronal degradation, in a subject comprising detecting the specific binding of a monoclonal antibody selected from the group consisting of ACI-1′

-Ab-9, ACI-12-Ab-11, functionally equivalent antibodies thereof and functional parts thereof, to an epitope of the amyloid protein in a sample or in situ which includes the steps of

(a) bringing the sample or a specific body part or body area suspected to contain the amyloid protein into contact with the antibody, wherein the antibody binds a conformational epitope of the amyloid protein;

(b) allowing the antibody to bind to any amyloid protein in the sample to form an immunological complex;

(c) detecting the formation of the immunological complex;

(d) correlating the presence or absence of the immunological complex with the presence or absence of amyloid protein in the sample or specific body part or area; and

(e) comparing the amount of said immunological complex to a normal control value,

wherein an increase in the amount of said complex compared to a normal control value indicates that the subject is suffering from or is at risk of developing an ocular disease associated with pathological abnormalities/changes in the tissues of the visual system, particularly associated with amyloid-beta-related pathological abnormalities/changes in the tissues of the visual system.

52. The method of claim 51, wherein the subject is a mammal.

53. The method of claim 52, wherein the mammal is a human.