ANTI-GB3 ANTIBODIES USEFUL IN TREATING DISORDERS ASSOCIATED WITH ANGIOGENESIS

• US 20140044721A1
• Filed: 02/07/2012
• Published: 02/13/2014
• Est. Priority Date: 02/07/2011
• Status: Abandoned Application

• Current Assignee: Institut de Radioprotection et de Sûreté Nucléaire, Universite De Nantes
• Original Assignee: Institut de Radioprotection et de Sûreté Nucléaire, Universite De Nantes
• Inventors: Aubry, Jacques, Paris, Franois, Birkle, Stephane, Desselle, Ariane, Gaugler, Marie-Hlne, Cochonneau, Denis, Chaumette, Tanguy
• Application Number:
  US13/983,937
• Publication Number:
  US 20140044721A1
• Time in Patent Office: Days
• US Class Current: 424/137.1
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/3084 against tumour-associated gangliosides
• CPC Class Codes: C07K 16/44 against material not provided for elsewhere , e.g. haptens, metals, DNA, RNA, amino acids
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• CPC Class Codes: C07K 2317/734 Complement-dependent cytotoxicity [CDC]
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value

Abstract

The present invention lies in the field of new cancer therapies, more precisely in the field of antiangiogenic compounds. It notably concerns anti-Gb3 antibodies having specific CDR sequences, as well as the use of anti-Gb3 antibodies not coupled to a therapeutic molecule in the treatment of diseases associated with angiogenesis, such as solid tumors.

Claims

1-21. -21. (canceled)

22. An antibody directed against the membrane glycosphingolipid globotriaosylceramide (Gb3), or a functional fragment or a derivative thereof, characterized in that it has at least one complementarity determining region (CDR) with an amino acid sequence selected from SEQ ID NO:

1 to 42, or with an amino acid sequence having at least 80% identity with one of SEQ ID NO;

1 to 42.

23. The antibody, functional fragment or derivative thereof according to claim 22, which has at least one heavy chain comprising at least one complementarity determining region (CDR) with an amino acid sequence selected from SEQ ID NO:

Ito 3, 7 to 9, 13 to 15, 19 to 21, to 27, 31 to 33, and 37 to 39, or with an amino acid sequence having at least 80%-identity with one of SEQ ID NO;

1 to 3, 7 to 9, 13 to 15, 19 to 21, 25 to 27, 31 to 33, and 37 to 39.

24. The antibody, functional fragment or derivative thereof according to claim 22, which has a light chain comprising at least one complementarity determining region (CDR) with an amino acid sequence selected from SEQ ID NO:

4 to 6, 10 to 12, 16 to 18, 22 to 24, 28 to 30, 34 to 36, and 40 to 42, or with an amino acid sequence having at least 80% identity with one of SEQ ID NO;

4 to 6, 10 to 12, 16 to 18, 22 to 24, 28 to 30, 34 to 36, and 40 to 42.

25. The antibody, functional fragment or derivative thereof according to claim 22, which has a heavy chain comprising three CDR-H (heavy chain CDR) with the following amino acid sequences, or sequences having at least 80% identity with the following sequences:

a) CDR1-H-3E2;

SEQ ID NO;

1, CDR2-H-3E2;

SEQ ID NO;

2, CDR3-H-3E2;

SEQ ID NO;

3,

b) CDR1-H-14C11;

SEQ ID NO;

7, CDR2-H-14C11;

SEQ ID NO;

8, CDR3-H-14C11;

SEQ ID NO;

9,

c) CDR1-H-15C11;

SEQ ID NO;

13, CDR2-H-15C11;

SEQ ID NO;

14, CDR3-H-15C11;

SEQ ID NO;

15,

d) CDR1-H-22F6;

SEQ ID NO;

19, CDR2-H-22F6;

SEQ ID NO;

20, CDR3-H-22F6;

SEQ ID NO;

21,

e) CDR1-H-25C10;

SEQ ID NO;

25, CDR2-H-25C10;

SEQ ID NO;

26, CDR3-H-25C10;

SEQ ID NO;

27,

f) CDR1-H-11E10;

SEQ ID NO;

31, CDR2-H-11E10;

SEQ ID NO;

32, CDR3-H-11E10;

SEQ ID NO;

33, or

g) CDR1-H-16G8;

SEQ ID NO;

37, CDR2-H-16G8;

SEQ ID NO;

38, CDR3-H-16G8;

SEQ ID NO;

39.

26. The antibody, functional fragment or derivative thereof according to claim 22, which has a light chain comprising three CDR-L (light chain CDR) with the following amino acid sequences, or sequences having at least 80% identity with the following sequences:

a) CDR1-L-3E2;

SEQ ID NO;

4, CDR2-L-3E2;

SEQ ID NO;

5, CDR3-L-3E2;

SEQ ID NO;

6,

b) CDR1-L-14C11;

SEQ ID NO;

10, CDR2-L-14C11;

SEQ ID NO;

11, CDR3-L-14C11;

SEQ ID NO;

12,

c) CDR1-L-15C11;

SEQ ID NO;

16, CDR2-L-15C11;

SEQ ID NO;

17, CDR3-L-15C11;

SEQ ID NO;

18,

d) CDR1-L-22F6;

SEQ ID NO;

22, CDR2-L-22F6;

SEQ ID NO;

23, CDR3-L-22F6;

SEQ ID NO;

24,

e) CDR1-L-25C10;

SEQ ID NO;

28, CDR2-L-25C10;

SEQ ID NO;

29, CDR3-L-25C10;

SEQ ID NO;

30,

f) CDR1-L-11E10;

SEQ ID NO;

34, CDR2-L-11E10;

SEQ ID NO;

35, CDR3-L-11E10;

SEQ ID NO;

36, or

g) CDR1-L-16G8;

SEQ ID NO;

40, CDR2-L-16G8;

SEQ ID NO;

41, CDR3-L-16G8;

SEQ ID NO;

42.

27. The antibody, functional fragment or derivative thereof according to claim 22, which has a heavy chain comprising a variable region with a sequence selected from SEQ ID NO:

43 to 49, or with a sequence having at least 80% identity with one of SEQ ID NO;

43 to 49.

28. The antibody, functional fragment or derivative thereof according to claim 22, which has a light chain comprising a variable region with a sequence selected from SEQ ID NO:

50 to 56, or with a sequence having at least 80% identity with one of SEQ ID NO;

50 to 56.

29. The antibody, functional fragment or derivative thereof according to claim 22, which has heavy and light chains whose variable regions have the following amino acid sequences, or sequences having at least 80% identity with the following sequences:

a) Antibody 3E2;

heavy chain;

SEQ ID NO;

43, light chain;

SEQ ID NO;

50,

b) Antibody 14C11;

heavy chain;

SEQ ID NO;

44, light chain;

SEQ ID NO;

51,

c) Antibody 15C11;

heavy chain;

SEQ ID NO;

45, light chain;

SEQ ID NO;

52,

d) Antibody 22F6;

heavy chain;

SEQ ID NO;

46, light chain;

SEQ ID NO;

53,

e) Antibody 25C10;

heavy chain;

SEQ ID NO;

47, light chain;

SEQ ID NO;

54,

f) Antibody 11E10;

heavy chain;

SEQ ID NO;

48, light chain;

SEQ ID NO;

55, and

g) Antibody 16G8;

heavy chain;

SEQ ID NO;

49, light chain;

SEQ ID NO;

56.

30. The antibody, functional fragment or derivative thereof according to claim 29, which has heavy and light chains whose variable regions have the following amino acid sequences, or sequences having at least 80%-identity with the following sequences:

a) Antibody 3E2;

heavy chain;

SEQ ID NO;

43, light chain;

SEQ ID NO;

50, and

b) Antibody 22F6;

heavy chain;

SEQ ID NO;

46, light chain;

SEQ ID NO;

53.

31. The antibody, functional fragment or derivative thereof according to claim 22, which is of isotype IgG or IgM.

32. The antibody, functional fragment or derivative thereof according to claim 22, which is a chimeric or humanized antibody.

33. The functional fragment of antibody according to claim 22, which is selected from fragments Fv, ScFv, Fab, F(ab′

)2, Fab′

, scFv-Fc or diabodies.

34. The antibody, functional fragment or derivative thereof according to claim 22, wherein said antibody, functional fragment or derivative thereof is not bound to a cytotoxic molecule.

35. A nucleic acid encoding the antibody according to claim 22.

36. A vector comprising a nucleic acid according to claim 35.

37. A host cell comprising the nucleic acid according to claim 35.

40. A method for treating a disease associated with angiogenesis in a subject in need thereof, comprising the administration of an effective quantity of an antibody directed against the membrane glycosphingolipid Gb3 and not coupled to a therapeutic molecule, wherein said antibody directed against the membrane glycosphingolipid Gb3 and not coupled to a therapeutic molecule is the antibody according to claim 35.

43. A host cell comprising the vector according to claim 36.

38. A method for treating a disease associated with angiogenesis in a subject in need thereof, comprising the administration of an effective quantity of an antibody directed against the membrane glycosphingolipid Gb3 and not coupled to a therapeutic molecule.

39. The method of claim 38, wherein said disease associated with angiogenesis is selected from solid tumors, psoriasis, angiomas, proliferative eye diseases, and autoimmune diseases.

41. The method according to claim 38, wherein said antibody directed against the membrane glycosphingolipid Gb3 and not coupled to a therapeutic molecule recognizes the upper band but not the lower band of the Gb3 doublet expressed by HMEC-1 cells.

42. A method to inhibit angiogenesis in a subject in need thereof, comprising the administration of an effective quantity of an antibody directed against the membrane glycosphingolipid Gb3 and not coupled to a therapeutic molecule.