Pd-1 / tigit binding proteins for cancer treatment

HK40137869APending Publication Date: 2026-09-18MEDIMMUNE LLC
View PDF 0 Cites 0 Cited by

Patent Information

Application Number
HK62026126944
Authority / Receiving Office
HK · HK
Patent Type
Applications
Current Assignee / Owner
Priority Date
2023-10-21
Filing Date
2026-07-31
Publication Date
2026-09-18
Estimated Expiration
2044-04-11

Smart Images

  • Figure 00000086_0000
    Figure 00000086_0000
  • Figure 00000087_0000
    Figure 00000087_0000
  • Figure 00000088_0000
    Figure 00000088_0000
Patent Text Reader

Abstract

The disclosure relates to methods of treating cancer by administering binding proteins, including antibodies, that bind to Programmed Death-1 ("PD-1") and T cell immunoreceptor with Ig and ITIM domains ("TIGIT") to a subject in an amount from about 70 mg to about 1500 mg.
Need to check novelty before this filing date? Find Prior Art

Description

This disclosure relates to a method of treating cancer by administering binding proteins (including antibodies) to a subject in doses of approximately 70 mg to approximately 1500 mg, these binding proteins binding to programmed death receptor-1 ("PD-1") and a T-cell immune receptor ("TIGIT") having Ig and ITIM domains. Abstract

Claims

CLAIMS1. A method for treating cancer in a subject, comprising administering to the subject a bispecific binding protein that specifically binds to Programed Death-1 (PD-1) and T cell immunoreceptor with Ig and ITIM domain (TIGIT) in an amount from about 70 mg to about 1500 mg, the bispecific binding protein comprising: a) a first binding domain that specifically binds to PD-1, wherein the first binding domain comprises a heavy chain variable domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 1, a HCDR2 having the amino acid sequence of SEQ ID NO: 2, and a HCDR3 having the amino acid sequence of SEQ ID NO: 3, and a light chain variable domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 4, a LCDR2 having the amino acid sequence of SEQ ID NO: 5 and a LCDR3 having the amino acid sequence of SEQ ID NO: 6; and b) a second binding domain that specifically binds to TIGIT, wherein the second binding domain comprises a heavy chain variable domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 11, a HCDR2 having the amino acid sequence of SEQ ID NO: 12, and a HCDR3 having the amino acid sequence of SEQ ID NO: 13, and a light chain variable domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 14, a LCDR2 having the amino acid sequence of SEQ ID NO: 15, and a LCDR3 having the amino acid sequence of SEQ ID NO: 16.

2. The method of claim 1, wherein the amount of bispecific binding protein administered is about 70 mg, about 150 mg, about 210 mg, about 450 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1250 mg, or about 1500 mg.

3. The method of claim 2, wherein the amount of bispecific binding protein administered is about 750 mg.

4. The method of claim 2, wherein the amount of bispecific binding protein administered is about 1500 mg.

5. The method of any of the previous claims, wherein the bispecific binding protein is administered once per treatment cycle.

6. The method of claim 5, wherein the treatment cycle is about 7 days, about 14 days, about 21 days, about 28 days, or about 35 days.

7. The method of claim 5, wherein the treatment cycle is about 7 days.

8. The method of any one of claims 5 to 7, wherein the treatment cycle is repeated for up to 35 cycles.

9. The method of any of the previous claims, wherein the bispecific binding protein is administered to the subject as a monotherapy.

10. The method of any one of the previous claims, wherein the bispecific binding protein is administered by an intravenous infusion (IV).

11. The method of any one of the previous claims, wherein the subject has not received a prior line of systemic therapy.

12. The method of any one of claims 1 to 10, wherein the subject has previously received a chemotherapy.

13. The method of any one of the previous claims, wherein the cancer comprises a cancer cell which expresses PD-L1.

14. The method of any one of claims 1 to 13, wherein the first binding domain of the bispecific binding protein that specifically binds to PD-1 comprises a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 7 and a light chain variable domain having the amino acid sequence of SEQ ID NO:9.

15. The method of any one of claims 1 to 13, wherein the first binding domain of the bispecific binding protein that specifically binds to PD-1 comprises a heavy chain variable domain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:7 and a light chain variable domain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:9.

16. The method of any one of claims 1 to 13, wherein the first binding domain of the bispecific binding protein that specifically binds to PD-1 comprises a heavy chain having the amino acid sequence of SEQ ID NO: 8 and a light chain having the amino acid sequence of SEQ ID NO: 10.

17. The method of any one of claims 1 to 13, wherein the first binding domain of the bispecific binding protein that specifically binds to PD-1 comprises a heavy chain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:8 and a light chain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 10.

18. The method of any one of claims 1 to 17, wherein the second binding domain of the bispecific binding protein that specifically binds to TIGIT comprises a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 17 and a light chain variable domain having the amino acid sequence of SEQ ID NO: 19.

19. The method of any one of claims 1 to 17, wherein the second binding domain of the bispecific binding protein that specifically binds to TIGIT comprises a heavy chain variable domain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 17 and a light chain variable domain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 19.

20. The method of any one of claims 1 to 17, wherein the second binding domain of the bispecific binding protein that specifically binds to TIGIT comprises a heavy chain having theamino sequence of SEQ ID NO: 18 and a light chain having the amino acid sequence of SEQ ID NO:20.

21. The method of any one of claims 1 to 17, wherein the second binding domain of the bispecific binding protein that specifically binds to TIGIT comprises a heavy chain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 18 and a light chain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:20.

22. The method of any one of the preceding claims, wherein the bispecific binding protein is a human or humanized bispecific antibody or antigen-binding fragment thereof.

23. The method of any of the preceding claims, wherein the bispecific binding protein comprises a variant Fc region.

24. The method of claim 23, wherein the variant Fc region of the bispecific binding protein comprises at least one substitution selected from 221K, 221Y, 225E, 225K, 225W, 228P, 234D, 234E, 234N, 234Q, 234T, 234H, 234Y, 2341, 234V, 234F, 235A, 235D, 235R, 235W, 235P, 235S, 235N, 235Q, 235T, 235H, 235Y, 2351, 235V, 235E, 235F, 236E, 237L, 237M, 237P, 239D, 239E, 239N, 239Q, 239F, 239T, 239H, 239Y, 2401, 240A, 240T, 240M, 241W, 241L, 241Y, 241E, 241R, 243W, 243L 243Y, 243R, 243Q, 244H, 245A, 247L, 247V, 247G, 250E, 250Q, 25 IF, 252L, 252Y, 254S, 254T, 255L, 256E, 256F, 256M, 257C, 257M, 257N, 2621, 262A, 262T, 262E, 2631, 263A, 263T, 263M, 264L, 2641, 264W, 264T, 264R, 264F, 264M, 264Y, 264E, 265A, 265G, 265N, 265Q, 265Y, 265F, 265V, 2651, 265L, 265H, 265T, 2661, 266A, 266T, 266M, 267Q, 267L, 268E, 269H, 269Y, 269F, 269R, 270E, 280A, 284M, 292P, 292L, 296E, 296Q, 296D, 296N, 296S, 296T, 296L, 2961, 296H, 296G, 297S, 297D, 297E, 298A, 298H, 2981, 298T, 298F, 2991, 299L, 299A, 299S, 299V, 299H, 299F, 299E, 3051, 308F, 313F, 316D, 318A, 318S, 320A, 320S, 322A, 322S, 325Q, 325L, 3251, 325D, 325E, 325A, 325T, 325V, 325H, 326A, 326D, 326E, 326G, 326M, 326V, 327G, 327W, 327N, 327L, 328S, 328M, 328D, 328E, 328N, 328Q, 328F, 3281, 328V, 328T, 328H, 328A, 329F, 329H, 329Q, 330K, 330G, 33OT, 330C, 33OL, 330Y, 330V, 3301, 330F, 33OR, 330H, 331G, 331A, 331L, 331M, 331F, 331W, 331K, 331Q, 331E, 331S, 331V,3311, 331C, 331Y, 331H, 331R, 331N, 331D, 331T, 332D, 332S, 332W, 332F, 332E, 332N, 332Q, 332T, 332H, 332Y, 332A, 333A, 333D, 333G, 333Q, 333S, 333V, 334A, 334E, 334H, 334L, 334M, 334Q, 334V, 334Y, 339T, 370E, 370N, 378D, 392T, 396L, 416G, 419H, 421K, 428L, 428F, 433K, 433L, 434A, 434W, 434Y, 436H, 440Y and 443W as numbered by the EU index as set forth in Kabat.

25. The method of claim 23, wherein the variant Fc region of the bispecific binding protein comprises one or more amino acid substitutions at positions selected from 428 and 434 as numbered by the EU index as set forth in Kabat.

26. The method of any one of claims 23 to 25, wherein the variant Fc region of the bispecific binding protein comprises one or more amino acid substitutions selected from 428L, 428F, 434A, 424F, 434W, and 434Y.

27. The method of any one of claims 23 to 26, wherein the variant Fc region of the bispecific binding protein comprises a YTE mutation.

28. The method of claim 23 or 24, wherein the Fc variant region of the bispecific binding protein comprises a L234F / L235E / P331 S triple mutation (TM).

29. The method of any one of claims 23 to 28, wherein the Fc region of the bispecific binding protein is aglycosylated.

30. The method of any one of claims 23 to 28, wherein the Fc region of the bispecific binding protein is deglycosylated.

31. The method of any one of claims 23 to 28, wherein the Fc region of the bispecific binding protein has reduced fucosylation or is afucosylated.

32. The method of any one of the preceding claims, wherein the bispecific binding protein comprises a kappa light chain constant region.

33. The method of any one of claims 1 to 32, wherein the bispecific binding protein comprises a lambda light chain constant region.

34. The method of any one of the preceding claims, wherein the bispecific binding protein is an antibody.

35. The method of claim 34, wherein the antibody is an IgG antibody.

36. The method of claim 35, wherein the antibody is an IgGl antibody.

37. The method of any one of claims 34 to 36, wherein the antibody is humanized.

38. The method of any of the preceding claims, wherein the cancer is one or more of ovarian cancer, breast cancer, colorectal cancer, prostate cancer, cervical cancer, uterine cancer, testicular cancer, bladder cancer, head and neck cancer, melanoma, pancreatic cancer, renal cell carcinoma, and lung cancer.

39. The method of claim 38, wherein the cancer is non-small cell lung cancer (NSCLC).

40. The method of claim 39, wherein the NSCLC is advanced or metastatic.

41. The method of claim 39, wherein the subject has a PD-L1 tumor proportion score of greater than or equal to 1%.

42. The method of claim 39, wherein the subject has a PD-L1 tumor proportion score of greater than or equal to 50%.

43. The method of any one of claims 39 to 42, wherein the subject is checkpoint inhibitor (CPI) naive.

44. A pharmaceutical composition comprising a bispecific binding protein that specifically binds to PD-1 and TIGIT in an amount from about 70 mg to about 1500 mg, the bispecific binding protein comprising: a) a first binding domain that specifically binds to PD-1, wherein the first binding domain comprises a heavy chain variable domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 1, a HCDR2 having the amino acid sequence of SEQ ID NO: 2, and a HCDR3 having the amino acid sequence of SEQ ID NO: 3, and a light chain variable domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 4, a LCDR2 having the amino acid sequence of SEQ ID NO: 5 and a LCDR3 having the amino acid sequence of SEQ ID NO: 6; and b) a second binding domain that specifically binds to TIGIT, wherein the second binding domain comprises a heavy chain variable domain comprising a HCDR1 having the amino acid sequence of SEQ ID NO: 11, a HCDR2 having the amino acid sequence of SEQ ID NO: 12, and a HCDR3 having the amino acid sequence of SEQ ID NO: 13, and a light chain variable domain comprising a LCDR1 having the amino acid sequence of SEQ ID NO: 14, a LCDR2 having the amino acid sequence of SEQ ID NO: 15, and a LCDR3 having the amino acid sequence of SEQ ID NO: 16.

45. The pharmaceutical composition of claim 44, wherein the pharmaceutical composition comprises about 70 mg, about 150 mg, about 210 mg, about 450 mg, about 750 mg, about 800 mg, about 850 mg, about 900 mg, about 950 mg, about 1000 mg, about 1250 mg, or about 1500 mg bispecific binding protein.

46. The pharmaceutical composition of claim 44, wherein the pharmaceutical composition comprises about 750 mg bispecific binding protein.

47. The pharmaceutical composition of claim 44, wherein the pharmaceutical composition comprises about 1500 mg bispecific binding protein.

48. The pharmaceutical composition of any one of claims 44 to 47, wherein the first binding domain of the bispecific binding protein that specifically binds to PD-1 comprises a heavychain variable domain having the amino acid sequence of SEQ ID NO:7 and a light chain variable domain having the amino acid sequence of SEQ ID NO:9.

49. The pharmaceutical composition of any one of claims 44 to 47, wherein the first binding domain of the bispecific binding protein that specifically binds to PD-1 comprises a heavy chain variable domain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 7 and a light chain variable domain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:9.

50. The pharmaceutical composition of any one of claims 44 to 47, wherein the first binding domain of the bispecific binding protein that specifically binds to PD-1 comprises a heavy chain having the amino acid sequence of SEQ ID NO: 8 and a light chain having the amino acid sequence of SEQ ID NO: 10.

51. The pharmaceutical composition of any one of claims 44 to 47, wherein the first binding domain of the bispecific binding protein that specifically binds to PD-1 comprises a heavy chain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 8 and a light chain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 10.

52. The pharmaceutical composition of any one of claims 44 to 47, wherein the second binding domain of the bispecific binding protein that specifically binds to TIGIT comprises a heavy chain variable domain having the amino acid sequence of SEQ ID NO: 17 and a light chain variable domain having the amino acid sequence of SEQ ID NO: 19.

53. The pharmaceutical composition of any one of claims 44 to 47, wherein the second binding domain of the bispecific binding protein that specifically binds to TIGIT comprises a heavy chain variable domain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 17 and a light chain variable domain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 19.

54. The pharmaceutical composition of any one of claims 44 to 47, wherein the second binding domain of the bispecific binding protein that specifically binds to TIGIT comprises a heavy chain having the amino sequence of SEQ ID NO: 18 and a light chain having the amino acid sequence of SEQ ID NO:20.

55. The pharmaceutical composition of any one of claims 44 to 47, wherein the second binding domain of the bispecific binding protein that specifically binds to TIGIT comprises a heavy chain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 18 and a light chain having an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO:20.

56. A kit comprising the pharmaceutical composition of any one of claims 44 to 55.

57. The kit of claim 56, further comprising instructions for administering the pharmaceutical composition.

58. A pharmaceutical composition as defined in any one of claims 44 to 55, for use in treating cancer.

59. The pharmaceutical composition for use of claim 58, wherein the cancer is one or more of ovarian cancer, breast cancer, colorectal cancer, prostate cancer, cervical cancer, uterine cancer, testicular cancer, bladder cancer, head and neck cancer, melanoma, pancreatic cancer, renal cell carcinoma, and lung cancer.

60. The pharmaceutical composition for use of claim 59, wherein the cancer is nonsmall cell lung cancer (NSCLC).

61. The pharmaceutical composition for use of claim 60, wherein the NSCLC is advanced or metastatic.

62. The pharmaceutical composition for use of claim 60 or 61, wherein the cancer has a PD-L1 tumor proportion score of greater than or equal to 1%.

63. The pharmaceutical composition for use of claim 60 or 61, wherein the cancer has a PD-L1 tumor proportion score of greater than or equal to 50%.

64. The pharmaceutical composition for use of any one of claims 60 to 63, wherein the cancer has not previously been treated with a checkpoint inhibitor.