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1. (WO2018106645) β-1,6-GLUCAN THERAPEUTIC ANTIBODY CONJUGATES
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CLAIMS

What is claimed is:

1. A composition comprising a therapeutic antibody conjugated to between 1 and 6 β-1,6-glucan oligomers, wherein each β-Ι,ό-glucan oligomer is independently comprised of between 2 and 10 glucose monomer units.

2. The composition of any preceding claim, wherein the β-Ι,ό-glucan oligomers are independently comprised of between 2 and 7 glucose monomer units.

3. The composition of any preceding claim, wherein the β-Ι,ό-glucan oligomers are independently comprised of between 5 and 8 glucose monomer units.

4. The composition of any preceding claim, wherein the β-Ι,ό-glucan oligomers are independently comprised of between 4 and 6 glucose monomer units.

5. The composition of any preceding claim, wherein the β-Ι,ό-glucan oligomers are each comprised of 8 glucose monomer units.

6. The composition of any preceding claim, wherein the β-Ι,ό-glucan oligomers are each comprised of 7 glucose monomer units.

7. The composition of any preceding claim, wherein the β-Ι,ό-glucan oligomers are each comprised of 6 glucose monomer units.

8. The composition of any preceding claim, wherein the β-Ι,ό-glucan oligomers are each comprised of 5 glucose monomer units.

9. The composition of any preceding claim, wherein the β-Ι,ό-glucan oligomers are each comprised of 4 glucose monomer units.

10. The composition of any preceding claim, wherein the β-Ι,ό-glucan oligomers are each comprised of 3 glucose monomer units.

11. The composition of any preceding claim, wherein the β-Ι,ό-glucan oligomers are each comprised of 2 glucose monomer units.

13. The composition of any preceding claim, wherein the antibody is conjugated to between 2 and 4 β-Ι,ό-glucan oligomers.

14. The composition of any preceding claim, wherein the antibody is conjugated to 3 β-1,6-glucan oligomers.

15. The composition of any preceding claim, wherein the antibody is conjugated to between 2 and 4 β-Ι,ό-glucan oligomers, and the β-Ι,ό-glucan oligomers are independently comprised of between 2 and 7glucose monomer units.

16. The composition of any preceding claim, wherein the antibody is conjugated to between 2 and 4 β-Ι,ό-glucan oligomers, and the β-Ι,ό-glucan oligomers are independently comprised of between 2 and 6 glucose monomer units.

17. The composition of any preceding claim, wherein the antibody is conjugated to between 2 and 4 β-Ι,ό-glucan oligomers, and the β-Ι,ό-glucan oligomers are independently comprised of between 5 and 8 glucose monomer units.

18. The composition of any preceding claim, wherein the antibody is conjugated to between 2 and 4 β-Ι,ό-glucan oligomers, and the β-Ι,ό-glucan oligomers are independently comprised of between 4 and 6 glucose monomer units.

19. The composition of any preceding claim, wherein the antibody is conjugated to between 2 and 4 β-Ι,ό-glucan oligomers, and the β-Ι,ό-glucan oligomers are each comprised of 6 glucose monomer units.

20. The composition of any preceding claim, wherein the antibody is conjugated to between 2 and 4 β-Ι,ό-glucan oligomers, and the β-Ι,ό-glucan oligomers are each comprised of 5 glucose monomer units.

21. The composition of any preceding claim, wherein the antibody is conjugated to between 2 and 4 β-Ι,ό-glucan oligomers, and the β-Ι,ό-glucan oligomers are each comprised of 4 glucose monomer units.

22. The composition of any preceding claim, wherein the antibody is conjugated to between 2 and 4 β-Ι,ό-glucan oligomers, and the β-Ι,ό-glucan oligomers are each comprised of 3 glucose monomer units.

23. The composition of any preceding claim, wherein the antibody is conjugated to between 2 and 4 β-Ι,ό-glucan oligomers, and the β-Ι,ό-glucan oligomers are each comprised of 2 glucose monomer units.

24. The composition of any preceding claim, wherein the antibody is conjugated to 3 β-1,6-glucan oligomers, and the β-Ι,ό-glucan oligomers are independently comprised of between 5 and 8 glucose monomer units.

25. The composition of any ] preceding claim, wherein the antibody is conjugated to 3 β-1,6-glucan oligomers, and the β-1,6-■g: lucan oligomers are independently comprised of between 2 and 6 glucose monomer units.

26. The composition of any preceding claim, wherein the antibody is conjugated to 3 β-1,6-glucan oligomers, and the β-Ι,ό-glucan oligomers are independently comprised of between 4 and 6 glucose monomer units.

27. The composition of any preceding claim, wherein the antibody is conjugated to 3 β-1,6-glucan oligomers, and the β-Ι,ό-glucan oligomers are each comprised of 8 glucose monomer units.

28. The composition of any preceding claim, wherein the antibody is conjugated to 3 β-1,6-glucan oligomers, and the β-Ι,ό-glucan oligomers are each comprised of 7 glucose monomer units.

29. The composition of any preceding claim, wherein the antibody is conjugated to 3 β-1,6-glucan oligomers, and the β-Ι,ό-glucan oligomers are each comprised of 6 glucose monomer units.

30. The composition of any preceding claim, wherein the antibody is conjugated to 3 β-1,6-glucan oligomers, and the β-Ι,ό-glucan oligomers are each comprised of 5 glucose monomer units.

31. The composition of any preceding claim, wherein the antibody is conjugated to 3 β-1,6-glucan oligomers, and the β-Ι,ό-glucan oligomers are each comprised of 4 glucose monomer units.

32. The composition of any preceding claim, wherein the antibody is conjugated to 3 β-1,6-glucan oligomers, and the β-Ι,ό-glucan oligomers are each comprised of 3 glucose monomer units.

33. The composition of any preceding claim, wherein the antibody is conjugated to 3 β-1,6-glucan oligomers, and the β-Ι,ό-glucan oligomers are each comprised of 2 glucose monomer units.

34. The composition of any preceding claim, wherein the antibody is conjugated to the β-1,6-glucan oligomers according to Formula II:


II

wherein:

Lys is a lysine residue;

b is between 1 and 6; and

^ is a compound of Formula I:


wherein:

a is between 1 and 9;

L is a linker; and

" represents a point of attachment between two atoms.

35. The composition of claim 15, wherein ^ is a compound of Formula la:


wherein:

a1 is between 1 and 9; and

" ^uw " represents a point of attachment between two atoms.

36. The composition of any one of the preceding claims, wherein the antibody comprises a variable domain having at least 80% identity with at least a portion of a sequence listed in Table I.

37. The composition of any one of the preceding claims, wherein the antibody comprises a heavy chain variable domain having at least 80%> identity with at least a portion of a heavy chain sequence listed in Table I.

38. The composition of any one of the preceding claims, wherein the antibody comprises a heavy chain having at least 80%> identity with a heavy chain sequence listed in Table I.

39. The composition of any one of the preceding claims, wherein the antibody comprises a light chain variable domain having at least 80% identity with at least a portion of a light chain sequence listed in Table I.

40. The composition any one of the preceding claims, wherein the antibody comprises a light chain having at least 80% identity with a light chain sequence listed in Table I.

41. The composition of any one of the preceding claims, wherein the antibody is selected

from the group consisting of cergutuzumab; ibritumomab tiuxetan; rituximab; tositumomab; gemtuzumab; alemtuzumab; panitumumab; depatuxizumab; sibrotuzumab; codrituzumab;

trastuzumab; patritumab; figitumumab; ganitumab; cantuzumab; ABX-MAl; bavituximab; J591; palivizumab; and bevacizumab.

42. The composition of any one of claims 1-40, wherein the antibody is a cergutuzumab antibody; a ibritumomab tiuxetan antibody; a rituximab antibody; a tositumomab antibody; a gemtuzumab antibody; an alemtuzumab antibody; a panitumumab antibody; a depatuxizumab antibody; a sibrotuzumab antibody; a codrituzumab antibody; a trastuzumab antibody; a patritumab antibody; a figitumumab antibody; a ganitumab antibody; a cantuzumab antibody; an ABX-MAl antibody; a bavituximab antibody; a J591 antibody; a palivizumab antibody; or a bevacizumab antibody.

43. The composition of claim 42, wherein the antibody competes with its parent therapeutic antibody for binding to a target.

44. The composition of any one of the preceding claims, wherein the β-Ι,ό-glucan oligomers are chemically synthesized.

45. The composition of any one of the preceding claims, wherein at least 90% of the dry weight of glucan contained in the composition is β-Ι,ό-glucan.

46. The composition of any one of the preceding claims, wherein less than 10% of the dry weight of glucan contained in the composition is P-l,3-glucan.

47. The composition of any one of the preceding claims, wherein the composition is substantially free of P-l,3-glucan.

48. A method of treating a cancer associated with overexpression and/or amplification of a target moeity in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a composition of any one of the preceding claims.

49. The method of claim 48, wherein the target is selected from the group consisting of CEACAM5, CD20, CD33, CD52, EGFR, EGFRVIII, FAP, Glycipan-3, HER2/neu, Her3, IGFIR (insulin-like growth factor-1 receptor), Mucl (CanAg), MUC18, Phosphatidyl Serine (PS), PSMA (prostate specific membrane antigen), RSV (A antigenic site of the F protein ), and VEGF-A.

50. The method of claim 48 or 49, wherein the target is a cell surface target.

51. The method of any one of claims 48-50, wherein the cancer is a breast cancer.

52. The method of any one of claims 48-50, wherein the cancer is a prostate cancer.

53. The method of any one of claims 48-50, wherein the cancer is an endometrial cancer.

54. The method of any one of claims 48-50, wherein the cancer is a gastric cancer.

55. The method of any one of claims 48-50, wherein the cancer is a bladder cancer.

56. The method of any one of claims 48-50, wherein the cancer is a lung cancer.

57. The method of claim 56, wherein the lung cancer is a non-small-cell lung cancer.

58. The method of any one of claims 48-50, wherein the cancer is an ovarian cancer.

59. The method of any one of claims 48-50, wherein the cancer is salivary gland cancer.

The method of any one of claims 48-50, wherein the cancer is pancreatic cancer.

The method of any one of claims 48-50, wherein the cancer is a blood cancer.

The method of any one of claims 48-50, wherein the cancer is a skin cancer.