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Last Updated: March 28, 2024

Claims for Patent: 7,696,320


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Summary for Patent: 7,696,320
Title:Ligands that have binding specificity for VEGF and/or EGFR and methods of use therefor
Abstract: Disclosed are ligands that have binding specificity for vascular endothelial growth factor (VEGF), for epidermal growth factor receptor (EGFR), or for VEGF and EGFR. Also disclosed are methods of using these ligands. In particular, the use of these ligands for cancer therapy is described.
Inventor(s): Ignatovich; Olga (Cambridge, GB), Holmes; Steve (Cambridge, GB), Beckmann; Roland (Geneva, CH), de Wildt; Rudolf M. T. (Cambridge, GB)
Assignee: Domantis Limited (GB)
Application Number:11/331,415
Patent Claims:1. A ligand that has binding specificity for vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR), comprising at least one immunoglobulin single variable domain that has a binding site with binding specificity for VEGF, wherein each said immunoglobulin single variable domain with binding specificity for VEGF comprises an amino acid sequence that has at least 95% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of TAR15-6 (SEQ ID NO:117), TAR15-8 (SEQ ID NO:119), and TAR15-26 (SEQ ID NO:123), and at least one immunoglobulin single variable domain that has a binding site with binding specificity for EGFR, wherein each said immunoglobulin single variable domain with binding specificity for EGFR comprises an amino acid sequence that has at least 95% amino acid sequence identity with the amino acid sequence of a dAb DOM16-39 (SEQ ID NO:345).

2. The ligand of claim 1, wherein each said immunoglobulin single variable domain that has a binding site with binding specificity for VEGF competes for binding to VEGF with bevacizumab.

3. The ligand of claim 1, wherein each said immunoglobulin single variable domain that has a binding site with binding specificity for EGFR competes for binding to EGFR with cetuximab.

4. A ligand that has binding specificity for vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR), comprising at least one immunoglobulin single variable domain with binding specificity for VEGF, wherein each said immunoglobulin single variable domain with binding specificity for VEGF competes for binding to VEGF with an anti-VEGF domain antibody (dAb) selected from the group consisting of TAR15-6 (SEQ ID NO:117), TAR15-8 (SEQ ID NO:119), and TAR15-26 (SEQ ID NO:123), and at least one immunoglobulin single variable domain with binding specificity for EGFR, wherein each said immunoglobulin single variable domain with binding specificity for EGFR competes for binding to EGFR with an anti-EGFR domain antibody (dAb) DOM16-39 (SEQ ID NO:345).

5. The ligand of claim 4, wherein each said immunoglobulin single variable domain with binding specificity for VEGF comprises an amino acid sequence that has at least 95% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of TAR15-6 (SEQ ID NO:117), TAR15-8 (SEQ ID NO:119), and TAR15-26 (SEQ ID NO:123).

6. The ligand of claim 1, wherein said ligand inhibits binding of epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) to EGFR.

7. The ligand of claim 1 wherein said ligand inhibits the activity of EGFR.

8. The ligand of claim 1, wherein said ligand inhibits the activity of EGFR without substantially inhibiting binding of epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) to EGFR.

9. The ligand of claim 1, wherein said ligand inhibits binding of VEGF to vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2).

10. The ligand of claim 1, wherein said ligand inhibits the activity of VEGF.

11. The ligand of claim 1, wherein said ligand inhibits the activity of VEGF without substantially inhibiting binding of VEGF to vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2).

12. The ligand of claim 1, wherein each said immunoglobulin single variable domain with binding specificity for VEGF is a V.sub.HH and wherein each said immunoglobulin single variable domain with binding specificity for EGFR is a V.sub.HH.

13. The ligand of claim 1, wherein each said immunoglobulin single variable domain with binding specificity for VEGF is selected from the group consisting of a human V.sub.H and a human V.sub.L and wherein each said immunoglobulin single variable domain with binding specificity for EGFR is selected from the group consisting of a human V.sub.H and a human V.sub.L.

14. The ligand of claim 1, wherein said ligand is an IgG-like format comprising two immunoglobulin single variable domains with binding specificity for VEGF, and two immunoglobulin single variable domains with binding specificity for EGFR.

15. The ligand of claim 1, wherein said ligand comprises an antibody Fc region.

16. A ligand that has binding specificity for vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR), comprising at least one immunoglobulin single variable domain with binding specificity for VEGF, wherein each said immunoglobulin single variable domain with binding specificity for VEGF competes for binding to VEGF with an anti-VEGF domain antibody (dAb) selected from the group consisting of TAR15-6 (SEQ ID NO:117), TAR15-8 (SEQ ID NO:119), and TAR15-26 (SEQ ID NO:123), and at least one immunoglobulin single variable domain with binding specificity for EGFR, wherein each said immunoglobulin single variable domain with binding specificity for EGFR competes for binding to EGFR with an anti-EGFR domain antibody (dAb) DOM16-39 (SEQ ID NO:345); and each said immunoglobulin single variable domain with binding specificity for EGFR competes for binding to EGFR with cetuximab.

17. The ligand of claim 16, wherein each said immunoglobulin single variable domain with binding specificity for VEGF comprises an amino acid sequence that has at least 95% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of TAR15-6 (SEQ ID NO:117), TAR15-8 (SEQ ID NO:119), and TAR15-26 (SEQ ID NO:123).

18. A ligand that has binding specificity for vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR), comprising a first immunoglobulin single variable domain with binding specificity for VEGF, wherein each said first immunoglobulin single variable domain with binding specificity for VEGF comprises an amino acid sequence that has at least 95% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of TAR15-6 (SEQ ID NO:117), TAR15-8 (SEQ ID NO:119), and TAR15-26 (SEQ ID NO:123), and a second immunoglobulin single variable domain with binding specificity for EGFR, wherein each said second immunoglobulin single variable domain with binding specificity for EGFR comprises an amino acid sequence that has at least 95% amino acid sequence identity with the amino acid sequence of a dAb DOM16-39 (SEQ ID NO:345), wherein said first immunoglobulin single variable domain competes for binding to VEGF with bevacizumab; and said second immunoglobulin single variable domain competes for binding to EGFR with cetuximab.

19. The ligand of claim 16, wherein said ligand inhibits binding of epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) to EGFR.

20. The ligand of claim 16, wherein said ligand inhibits the activity of EGFR.

21. The ligand of claim 16, wherein said ligand inhibits the activity of EGFR without substantially inhibiting binding of epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha) to EGFR.

22. The ligand of claim 16, wherein said ligand inhibits binding of VEGF to vascular endothelial growth factor receptor 1 (VEGFR 1) and vascular endothelial growth factor receptor 2 (VEGFR2).

23. The ligand of claim 16, wherein said ligand inhibits the activity of VEGF.

24. The ligand of claim 16, wherein said ligand inhibits the activity of VEGF without substantially inhibiting binding of VEGF to vascular endothelial growth factor receptor 1 (VEGFR1) and vascular endothelial growth factor receptor 2 (VEGFR2).

25. The ligand of claim 16, wherein each said immunoglobulin single variable domain with binding specificity for VEGF is a V.sub.HH and wherein each said an immunoglobulin single variable domain with binding specificity for EGFR is a V.sub.HH.

26. The ligand of claim 16, wherein each said immunoglobulin single variable domain with binding specificity for VEGF is selected from the group consisting of a human V.sub.H and a human V.sub.L, and each said immunoglobulin single variable domain with binding specificity for EGFR is selected from the group consisting of a human V.sub.H and a human V.sub.L.

27. The ligand of claim 16, wherein said ligand is an IgG-like format comprising two immunoglobulin single variable domains with binding specificity for VEGF, and two immunoglobulin single variable domains with binding specificity for EGFR.

28. The ligand of claim 16, wherein said ligand comprises an antibody Fc region.

29. A ligand that has binding specificity for vascular endothelial growth factor (VEGF), comprising at least one immunoglobulin single variable domain with binding specificity for VEGF, wherein each said immunoglobulin single variable domain with binding specificity for VEGF competes for binding to VEGF with an anti-VEGF domain antibody (dAb) selected from the group consisting of TAR15-6 (SEQ ID NO:117), TAR15-8 (SEQ ID NO:119), and TAR15-26 (SEQ ID NO:123).

30. The ligand of claim 29, wherein said ligand inhibits binding of VEGF to vascular endothelial growth factor receptor 1 (VEGFR 1) and vascular endothelial growth factor receptor 2 (VEGFR2).

31. The ligand of claim 29, wherein each said immunoglobulin single variable domain with binding specificity for VEGF is a V.sub.HH.

32. The ligand of claim 29, wherein each said immunoglobulin single variable domain with binding specificity for VEGF is selected from the group consisting of a human V.sub.H and a human V.sub.L.

33. The ligand of claim 29, wherein each said immunoglobulin single variable domain with binding specificity for VEGF comprises an amino acid sequence that has at least 95% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of TAR15-6 (SEQ ID NO:117), TAR15-8 (SEQ ID NO:119), and TAR15-26 (SEQ ID NO:123).

34. The ligand of claim 1, wherein said ligand further comprises a toxin.

35. The ligand of claim 34, wherein said toxin is a surface active toxin.

36. The ligand of claim 35, wherein said surface active toxin comprises a free radical generator or a radionuclide.

37. The ligand of claim 34, wherein said toxin is a cytotoxin, free radical generator, antimetabolite, protein, polypeptide, peptide, photoactive agent, chemotherapeutic, radionuclide or intrabody.

38. The ligand of claim 1, wherein said ligand further comprises a half-life extending moiety.

39. The ligand of claim 38, wherein said half-life extending moiety is a polyalkylene glycol moiety, serum albumin or a fragment thereof, transfeffin receptor or a transferrin-binding portion thereof, or a moiety comprising a binding site for a polypeptide that enhances half-life in vivo.

40. The ligand of claim 39, wherein said half-life extending moiety is a moiety comprising a binding site for a polypeptide that enhances half-life in vivo, said moiety being selected from the group consisting of an affibody, an SpA domain, an LDL receptor class A domain, an EGF domain, and an avimer.

41. The ligand of claim 39, wherein said half-life extending moiety is a polyethylene glycol moiety.

42. The ligand of claim 39, wherein said half-life extending moiety is an antibody or antibody fragment comprising a binding site for serum albumin or neonatal Fc receptor.

43. The ligand of claim 42, wherein said antibody or antibody fragment comprising a binding site for serum albumin or neonatal Fc receptor is an antibody fragment, and said antibody fragment is an immunoglobulin single variable domain comprising a binding site for serum albumin.

44. The ligand of claim 43, wherein said immunoglobulin single variable domain comprising a binding site for serum albumin competes for binding to human serum albumin with a dAb selected from the group consisting of DOM7m-16 (SEQ ID NO:473), DOM7m-12 (SEQ ID NO: 474), DOM7m-26 (SEQ ID NO: 475), DOM7r-1 (SEQ ID NO: 476), DOM7r-3 (SEQ ID NO: 477), DOM7r-4 (SEQ ID NO: 478), DOM7r-5 (SEQ ID NO: 479), DOM7r-7 (SEQ ID NO: 480), DOM7r-8 (SEQ ID NO: 481), DOM7h-2 (SEQ ID NO: 482), DOM7h-3 (SEQ ID NO: 483), DOM7h-4 (SEQ ID NO: 484), DOM7h-6 (SEQ ID NO: 485), DOM7h-1 (SEQ ID NO: 486), DOM7h-7 (SEQ ID NO: 487), DOM7h-22 (SEQ ID NO: 489), DOM7h-23 (SEQ ID NO: 490), DOM7h-24 (SEQ ID NO: 491), DOM7h-25 (SEQ ID NO: 492), DOM7h-26 (SEQ ID NO: 493), DOM7h-21 (SEQ ID NO: 494), DOM7h-27 (SEQ ID NO: 495), DOM7h-8 (SEQ ID NO: 496), DOM7r-13 (SEQ ID NO: 497), DOM7r-14 (SEQ ID NO: 498), DOM7r-15 (SEQ ID NO: 499), DOM7r-16 (SEQ ID NO: 500), DOM7r-17 (SEQ ID NO: 501), DOM7r-18 (SEQ ID NO: 502), DOM7r-19 (SEQ ID NO: 503), DOM7r-20 (SEQ ID NO: 504), DOM7r-21 (SEQ ID NO: 505), DOM7r-22 (SEQ ID NO: 506), DOM7r-23 (SEQ ID NO: 507), DOM7r-24 (SEQ ID NO: 508), DOM7r-25 (SEQ ID NO: 509), DOM7r-26 (SEQ ID NO: 510), DOM7r-27 (SEQ ID NO: 511), DOM7r-28 (SEQ ID NO: 512), DOM7r-29 (SEQ ID NO: 513), DOM7r-30 (SEQ ID NO: 514), DOM7r-31 (SEQ ID NO: 515), DOM7r-32 (SEQ ID NO: 516), and DOM7r-33 (SEQ ID NO: 517).

45. The ligand of claim 43, wherein said immunoglobulin single variable domain comprising a binding site for serum albumin comprises an amino acid sequence that has at least 95% amino acid sequence identity with the amino acid sequence of a dAb selected from the group consisting of DOM7m-16 (SEQ ID NO: 473), DOM7m-12 (SEQ ID NO: 474), DOM7m-26 (SEQ ID NO: 475), DOM7r-1 (SEQ ID NO: 476), DOM7r-3 (SEQ ID NO: 477), DOM7r-4 (SEQ ID NO: 478), DOM7r-5 (SEQ ID NO: 479), DOM7r-7 (SEQ ID NO: 480), DOM7r-8 (SEQ ID NO: 481), DOM7h-2 (SEQ ID NO: 482), DOM7h-3 (SEQ ID NO: 483), DOM7h-4 (SEQ ID NO: 484), DOM7h-6 (SEQ ID NO: 485), DOM7h-1 (SEQ ID NO: 486), DOM7h-7 (SEQ ID NO: 487), DOM7h-22 (SEQ ID NO: 489), DOM7h-23 (SEQ ID NO: 490), DOM7h-24 (SEQ ID NO: 491), DOM7h-25 (SEQ ID NO: 492), DOM7h-26 (SEQ ID NO: 493), DOM7h-21 (SEQ ID NO: 494), DOM7h-27 (SEQ ID NO: 495), DOM7h-8 (SEQ ID NO: 496), DOM7r-13 (SEQ ID NO: 497), DOM7r-14 (SEQ ID NO: 498), DOM7r-15 (SEQ ID NO: 499), DOM7r-16 (SEQ ID NO: 500), DOM7r-17 (SEQ ID NO: 501), DOM7r-18 (SEQ ID NO: 502), DOM7r-19 (SEQ ID NO: 503), DOM7r-20 (SEQ ID NO: 504), DOM7r-21 (SEQ ID NO: 505), DOM7r-22 (SEQ ID NO: 506), DOM7r-23 (SEQ ID NO: 507), DOM7r-24 (SEQ ID NO: 508), DOM7r-25 (SEQ ID NO: 509), DOM7r-26 (SEQ ID NO: 510), DOM7r-27 (SEQ ID NO: 511), DOM7r-28 (SEQ ID NO: 512), DOM7r-29 (SEQ ID NO: 513), DOM7r-30 (SEQ ID NO: 514), DOM7r-31 (SEQ ID NO: 515), DOM7r-32 (SEQ ID NO: 516), and DOM7r-33 (SEQ ID NO: 517).

46. A composition comprising a ligand of claim 1 or 29 and a physiologically acceptable carrier.

47. A composition comprising a single domain antibody polypeptide construct that antagonizes human VEGF binding to a receptor, wherein said single domain antibody polypeptide construct comprises a CDR1, CDR2, and CDR3 sequence that is the same as the sequence of CDR1, CDR2, and CDR3 of a dAb selected from the group consisting of TAR15-1 (SEQ ID NO:100), TAR15-3 (SEQ ID NO:101), TAR15-4 (SEQ ID NO:102), TAR15-9 (SEQ ID NO:103), TAR15-10 (SEQ ID NO:104), TAR15-11 (SEQ ID NO:105), TAR15-12 (SEQ ID NO:106), TAR15-13 (SEQ ID NO:107), TAR15-14 (SEQ ID NO:108), TAR15-15 (SEQ ID NO:109), TAR15-16 (SEQ ID NO:110), TAR15-17 (SEQ ID NO:111), TAR15-18 (SEQ ID NO:112), TAR15-19 (SEQ ID NO:113), TAR15-20 (SEQ ID NO:114), TAR15-22 (SEQ ID NO:115), TAR15-5 (SEQ ID NO:116), TAR15-6 (SEQ ID NO:117), TAR15-7 (SEQ ID NO:118), TAR15-8 (SEQ ID NO:119), TAR15-23 (SEQ ID NO:120), TAR15-24 (SEQ ID NO:121), TAR15-25 (SEQ ID NO:122), TAR15-26 (SEQ ID NO:123), TAR15-27 (SEQ ID NO:124), TAR15-29 (SEQ ID NO:125), and TAR15-30 (SEQ ID NO:126).

48. A composition comprising a single domain antibody polypeptide construct that antagonizes human VEGF binding to a receptor, wherein said single domain antibody polypeptide construct comprises an amino acid sequence selected from the group consisting of TAR15-1 (SEQ ID NO:100), TAR15-3 (SEQ ID NO:101), TAR15-4 (SEQ ID NO:102), TAR15-9 (SEQ ID NO:103), TAR15-10 (SEQ ID NO:104), TAR15-11 (SEQ ID NO:105), TAR15-12 (SEQ ID NO:106), TAR15-13 (SEQ ID NO:107), TAR15-14 (SEQ ID NO:108), TAR15-15 (SEQ ID NO:109), TAR15-16 (SEQ ID NO:110), TAR15-17 (SEQ ID NO:111), TAR15-18 (SEQ ID NO:112), TAR15-19 (SEQ ID NO:113), TAR15-20 (SEQ ID NO:114), TAR 15-22 (SEQ ID NO:115), TAR15-5 (SEQ ID NO:116), TAR15-6 (SEQ ID NO:117), TAR15-7 (SEQ ID NO:118), TAR15-8 (SEQ ID NO:119), TAR15-23 (SEQ ID NO:120), TAR15-24 (SEQ ID NO:121), TAR15-25 (SEQ ID NO:122), TAR15-26 (SEQ ID NO:123), TAR15-27 (SEQ ID NO:124), TAR15-29 (SEQ ID NO:125), and TAR15-30 (SEQ ID NO:126) or a sequence at least 95% identical thereto.

49. A composition of claim 47 wherein said single domain antibody polypeptide construct comprises a tetravalent, dual-specific antibody polypeptide construct comprising: a) a first copy of a first fusion protein comprising a single domain antibody polypeptide that binds a first epitope, fused to an IgG heavy chain constant domain; b) a second copy of said first fusion protein; c) a first copy of a second fusion protein comprising a single domain antibody polypeptide that binds a second epitope, fused to a light chain constant domain; d) a second copy of said second fusion protein; wherein said first and said second copies of said first fusion protein are disulfide bonded to each other via their respective IgG heavy chain constant domains, and wherein said light chain constant domain of said first copy of said second fusion protein is disulfide bonded to the IgG heavy chain constant domain of said first copy of said first fusion protein, and wherein said light chain constant domain of said second copy of second fusion protein is disulfide bonded to the IgG heavy chain constant domain of said second copy of said first fusion protein, and wherein said polypeptide construct binds said first and said second epitopes.

50. The composition of claim 49 wherein said first and said second epitope is a VEGF epitope.

51. The ligand and of claim 4, wherein each said immunoglobulin single variable domain with binding specificity for EGFR comprises an amino acid sequence that has at least 95% amino acid sequence identity with the amino acid sequence of a dAb DOM16- 39 (SEQ ID NO:345).

52. The ligand of claim 1, wherein said ligand inhibits binding of epidermal growth factor (EGF) or transforming growth factor alpha (TGFalpha) to EGFR.

53. The ligand of claim 1, wherein said ligand inhibits the activity of EGFR without substantially inhibiting binding of epidermal growth factor (EGF) or transforming growth factor alpha (TGFalpha) to EGFR.

54. The ligand of claim 1, wherein said ligand inhibits binding of VEGF to vascular endothelial growth factor receptor 1 (VEGFR1) or vascular endothelial growth factor receptor 2 (VEGFR2).

55. The ligand of claim 1, wherein said ligand inhibits the activity of VEGF without substantially inhibiting binding of VEGF to vascular endothelial growth factor receptor 1 (VEGFR1) or vascular endothelial growth factor receptor 2 (VEGFR2).

56. The ligand of claim 1, wherein each said immunoglobulin single variable domain with binding specificity for VEGF is a V.sub.HH or wherein each said immunoglobulin single variable domain with binding specificity for EGFR is a V.sub.HH.

57. The ligand of claim 16, wherein said ligand inhibits binding of epidermal growth factor (EGF) or transforming growth factor alpha (TGFalpha) to EGFR.

58. The ligand of claim 16, wherein said ligand inhibits the activity of EGFR without substantially inhibiting binding of epidermal growth factor (EGF) or transforming growth factor alpha (TGFalpha) to EGFR.

59. The ligand of claim 16, wherein said ligand inhibits binding of VEGF to vascular endothelial growth factor receptor 1 (VEGFR1) or vascular endothelial growth factor receptor 2 (VEGFR2).

60. The ligand of claim 16, wherein said ligand inhibits the activity of VEGF without substantially inhibiting binding of VEGF to vascular endothelial growth factor receptor 1 (VEGFR1) or vascular endothelial growth factor receptor 2 (VEGFR2).

61. The ligand of claim 16, wherein each said immunoglobulin single variable domain with binding specificity for VEGF is a V.sub.HH or wherein each said an immunoglobulin single variable domain with binding specificity for EGFR is a V.sub.HH.

62. The ligand of claim 29, wherein said ligand inhibits binding of VEGF to vascular endothelial growth factor receptor 1 (VEGFR1) or vascular endothelial growth factor receptor 2 (VEGFR2).

63. The composition of claim 49 wherein said first or said second epitope is a VEGF epitope.

64. A composition comprising a single domain antibody polypeptide construct that antagonizes human VEGF binding to a receptor, wherein said single domain antibody polypeptide construct competes for binding to VEGF with a single domain antibody polypeptide construct selected from the group consisting of: TAR15-1 (SEQ ID NO:100), TAR15-3 (SEQ ID NO:101), TAR15-4 (SEQ ID NO:102), TAR15-9 (SEQ ID NO:103), TAR15-10 (SEQ ID NO:104), TAR15-11 (SEQ ID NO:105), TAR15-12 (SEQ ID NO:106), TAR15-13 (SEQ ID NO:107), TAR15-14 (SEQ ID NO:108), TAR15-15 (SEQ ID NO:109), TAR15-16 (SEQ ID NO:110), TAR15-17 (SEQ ID NO:111), TAR15-18 (SEQ ID NO:112), TAR15-19 (SEQ ID NO:113), TAR15-20 (SEQ ID NO:114), TAR15-22 (SEQ ID NO:115), TAR15-5 (SEQ ID NO:116), TAR15-6 (SEQ ID NO:117), TAR15-7 (SEQ ID NO:118), TAR15-8 (SEQ ID NO:119), TAR15-23 (SEQ ID NO:120), TAR15-24 (SEQ ID NO:121), TAR15-25 (SEQ ID NO:122), TAR15-26 (SEQ ID NO:123), TAR15-27 (SEQ ID NO:124), TAR15-29 (SEQ ID NO:125), and TAR15-30 (SEQ ID NO:126).

65. A composition comprising a single domain antibody polypeptide construct that antagonizes human VEGF binding to a receptor, wherein said single domain antibody polypeptide construct competes for binding to VEGF with a single domain antibody polypeptide construct selected from the group consisting of: TAR15-6-500 (SEQ ID NO:127), TAR15-6-501 (SEQ ID NO:128), TAR15-6-502 (SEQ ID NO:129), TAR15-6-503 (SEQ ID NO:130), TAR15- 6-504 (SEQ ID NO:13 1), TAR15-6-505 (SEQ ID NO:132), TAR15-6-506 (SEQ ID NO:133), TAR15-6-507 (SEQ ID NO:134), TAR15-6-508 (SEQ ID NO:135), TAR15-6-509 (SEQ ID NO:136), TAR15-6-510 (SEQ ID NO:137), TAR15-8-500 (SEQ ID NO:138), TAR15-8-501 (SEQ ID NO:139), TAR15-8-502 (SEQ ID NO:140), TAR15-8-503 (SEQ ID NO:141), TAR15- 8-505 (SEQ ID NO:142), TAR15-8-506 (SEQ ID NO:143), TAR15-8-507 (SEQ ID NO:144), TAR15-8-508 (SEQ ID NO:145), TAR15-8-509 (SEQ ID NO:146), TAR15-8-510 (SEQ ID NO:147), TAR15-8-511 (SEQ ID NO:148), TAR15-26-500 (SEQ ID NO:149), TAR15-26-501 (SEQ ID NO:150), TAR15-26-502 (SEQ ID NO:15 1), TAR15-26-503 (SEQ ID NO:152), TAR15-26-504 (SEQ ID NO:153), TAR15-26-505 (SEQ ID NO:154), TAR15-26-506 (SEQ ID NO:155), TAR15-26-507 (SEQ ID NO:156), TAR15-26-508 (SEQ ID NO:157), TAR15-26-509 (SEQ ID NO:158), TAR15-26-510 (SEQ ID NO:159), TAR15-26-511 (SEQ ID NO:160), TAR15-26-512 (SEQ ID NO:161), TAR15-26-513 (SEQ ID NO:162), TAR15-26-514 (SEQ ID NO:163), TAR15-26-515 (SEQ ID NO:164), TAR15-26-516 (SEQ ID NO:165), TAR15-26-517 (SEQ ID NO:166), TAR15-26-518 (SEQ ID NO:167), TAR15-26-519 (SEQ ID NO:168), TAR15-26-520 (SEQ ID NO:169), TAR15-26-521 (SEQ ID NO: 170), TAR15-26-522 (SEQ ID NO:171), TAR15-26-523 (SEQ ID NO:172), TAR15-26-524 (SEQ ID NO:173), TAR15-26-525 (SEQ ID NO:174), TAR15-26-526 (SEQ ID NO:175), TAR15-26-527 (SEQ ID NO:176), TAR15-26-528 (SEQ ID NO:177), TAR15-26-529 (SEQ ID NO: 178), TAR15-26-530 (SEQ ID NO:179), TAR15-26-531 (SEQ ID NO:180), TAR15-26-532 (SEQ ID NO:181), TAR15-26-533 (SEQ ID NO:182), TAR15-26-534 (SEQ ID NO:183), TAR15-26-535 (SEQ ID NO:184), TAR15-26-536 (SEQ ID NO:185), TAR15-26-537 (SEQ ID NO:186), TAR15-26-538 (SEQ ID NO:187), TAR15-26-539 (SEQ ID NO:188), TAR15-26-540 (SEQ ID NO:189), TAR15-26-541 (SEQ ID NO:190), TAR15-26-542 (SEQ ID NO:191), TAR15-26-543 (SEQ ID NO:192), TAR15-26-544 (SEQ ID NO:193), TAR15-26-545 (SEQ ID NO:194), TAR15-26-546 (SEQ ID NO:195), TAR15-26-547 (SEQ ID NO:196), TAR15-26-548 (SEQ ID NO:197), TAR15-26-549 (SEQ ID NO:198), TAR15-26-550 (SEQ ID NO:539), and TAR15-26-551 (SEQ ID NO:540).

Details for Patent 7,696,320

Applicant Tradename Biologic Ingredient Dosage Form BLA Approval Date Patent No. Expiredate
Eli Lilly And Company ERBITUX cetuximab Injection 125084 02/12/2004 ⤷  Try a Trial 2024-08-24
Eli Lilly And Company ERBITUX cetuximab Injection 125084 03/28/2007 ⤷  Try a Trial 2024-08-24
Genentech, Inc. AVASTIN bevacizumab Injection 125085 02/26/2004 ⤷  Try a Trial 2024-08-24
>Applicant >Tradename >Biologic Ingredient >Dosage Form >BLA >Approval Date >Patent No. >Expiredate

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