IP Library › Granted Patent US 12,215,161
Granted Patent B2
US 12,215,161 · App. 17/817,295 · Granted Feb 4, 2025

Combination therapies and patient stratification with bispecific anti-EGFR/c-Met antibodies

Inventors: Sheri Moores (Wayne, PA); Smruthi Vijayaraghavan (Spring House, PA)
Assignee: Janssen Biotech, Inc.
C07K16/2863A61K45/06C07K2317/31C07K2317/565
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,215,161
App. No.
17/817,295
Granted
Feb 4, 2025
Kind
B2
Abstract

The present invention relates to combination therapies and patient stratification with bispecific anti-EGFR/c-Met antibodies.

Claims (89)

1. A method of inducing trogocytosis from a donor cancer cell that expresses EGFR, c-Met, or EGFR and c-Met to an acceptor macrophage cell or an acceptor monocyte cell, the method comprising contacting the donor cancer cell with a bispecific anti-EGFR/c-Met antibody for a time sufficient to induce trogocytosis from the donor cancer cell to the acceptor macrophage cell or the acceptor monocyte cell,

wherein the bispecific anti-EGFR/c-Met antibody comprises:

a first domain that binds EGFR, wherein the first domain comprises a heavy chain complementarity determining region (HCDR1) comprising the amino acid sequence of SEQ ID NO: 1, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 2, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 3, a light chain complementarity determining region 1 (LCDR1) comprising the amino acid sequence of SEQ ID NO: 4, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 5, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 6; and

a second domain that binds c-Met, wherein the second domain comprises a HCDR1 comprising the amino acid sequence of SEQ ID NO: 7, a HCDR2 comprising the amino acid sequence of SEQ ID NO: 8, a HCDR3 comprising the amino acid sequence of SEQ ID NO: 9, a LCDR1 comprising the amino acid sequence of SEQ ID NO: 10, a LCDR2 comprising the amino acid sequence of SEQ ID NO: 11, and a LCDR3 comprising the amino acid sequence of SEQ ID NO: 12.

2. The method of claim 1 , wherein

the first domain that binds EGFR comprises a VH comprising the amino acid sequence of SEQ ID NO: 13 and a VL comprising the amino acid sequence of SEQ ID NO: 14; and

the second domain that binds c-Met comprises a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 16.

3. The method of claim 2 , wherein the bispecific anti-EGFR/c-Met antibody is an IgG1 isotype.

4. The method of claim 3 , wherein the bispecific anti-EGFR/c-Met antibody comprises a HC1 comprising the amino acid sequence of SEQ ID NO: 17, a LC1 comprising the amino acid sequence of SEQ ID NO: 18, a HC2 comprising the amino acid sequence of SEQ ID NO: 19, and a LC2 comprising the amino acid sequence of SEQ ID NO: 20.

5. The method of claim 4 , wherein the donor cancer cell has a wild-type EGFR, an EGFR activating mutation, an EGFR gene amplification, increased levels of circulating HGF, a wild-type c-Met, a c-Met activating mutation, a c-Met gene amplification, or a mutant KRAS.

6. The method of claim 5 , wherein the EGFR activating mutation comprises a L718Q, G719A, G719X (X being any amino acid), L861X (X being any amino acid), L858R, E746K, L747S, E749Q, A750P, A755V, V765M, C797S, L858P, or T790M substitution, deletion of E746-A750, deletion of R748-P753, insertion of Ala (A) between M766 and A767, insertion of Ser, Val, and Ala (SVA) between S768 and V769, insertion of Asn and Ser (NS) between P772 and H773, insertion of one or more amino acids between D761 and E762, A763 and Y764, Y764 and Y765, M766 and A767, A767 and V768, S768 and V769, V769 and D770, D770 and N771, N771 and P772, P772 and H773, H773 and V774, V774 and C775, one or more deletions in EGFR exon 20, one or more insertions in EGFR exon 20, or any combination thereof.

7. The method of claim 5 , wherein the mutant KRAS comprises a G12V, G12C, or G12A substitution.

8. The method of claim 1 , wherein the contacting step is done in vitro.

9. The method of claim 1 , wherein the contacting step comprises administering the bispecific anti-EGFR/c-Met antibody to a subject.

10. The method of claim 9 , wherein the subject has an EGFR, c-Met, or EGFR and c-Met expressing cancer.

11. The method of claim 10 , wherein the subject has a newly diagnosed EGFR, c-Met, or EGFR and c-Met expressing cancer.

12. The method of claim 10 , wherein the subject is resistant or has acquired resistance to treatment with a prior anti-cancer therapy.

13. The method of claim 12 , wherein the prior anti-cancer therapy is a chemotherapy, a targeted anti-cancer therapy, or a kinase inhibitor.

14. The method of claim 13 , wherein the kinase inhibitor is an inhibitor of EGFR, c-Met, HER2, HER3, HER4, VEGFR, or AXL.

15. The method of claim 13 , wherein the kinase inhibitor is erlotinib, gefitinib, lapatinib, vandetanib, afatinib, osimertinib, lazertinib, poziotinib, criotinib, cabozantinib, capmatinib, axitinib, lenvatinib, nintedanib, regorafenib, pazopanib, sorafenib, or sunitinib.

16. The method of claim 10 , wherein the cancer cell expressing EGFR, c-Met, or EGFR and c-Met is derived from epithelial cell cancer, breast cancer, ovarian cancer, lung cancer, non-small cell lung cancer (NSCLC), lung adenocarcinoma, small cell lung cancer, colorectal cancer, anal cancer, prostate cancer, kidney cancer, bladder cancer, head and neck cancer, pharynx cancer, cancer of the nose, pancreatic cancer, skin cancer, oral cancer, cancer of the tongue, esophageal cancer, vaginal cancer, cervical cancer, cancer of the spleen, testicular cancer, gastric cancer, cancer of the thymus, colon cancer, thyroid cancer, liver cancer, HCC, or sporadic or hereditary papillary renal cell carcinoma PRCC.

17. The method of claim 16 , comprising further administering one or more anti-cancer therapies to the subject.

18. The method of claim 17 , wherein the one or more anti-cancer therapies comprise a chemotherapy, a targeted anti-cancer therapy, or a kinase inhibitor.

19. The method of claim 18 , wherein the kinase inhibitor is an inhibitor of EGFR, c-Met, HER2, HER3, HER4, VEGFR, or AXL.

20. The method of claim 19 , wherein the kinase inhibitor is erlotinib, gefitinib, lapatinib, vandetanib, afatinib, osimertinib, lazertinib, poziotinib, criotinib, cabozantinib, capmatinib, axitinib, lenvatinib, nintedanib, regorafenib, pazopanib, sorafenib, or sunitinib.

21. The method of claim 20 , wherein the kinase inhibitor is lazertinib.

22. The method of claim 1 , wherein the acceptor cell is the macrophage cell.

23. The method of claim 1 , wherein the acceptor cell is the monocyte cell.

24. The method of claim 6 , wherein the EGFR activating mutation comprises one or more insertions in EGFR exon 20.

25. The method of claim 6 , wherein the EGFR activating mutation comprises L858R, deletion of E746-A750, or deletion of R748-P753.

26. The method of claim 25 , wherein the EGFR activating mutation comprises L858R.

27. The method of claim 25 , wherein the EGFR activating mutation comprises deletion of E746-A750, or deletion of R748-P753.

28. The method of claim 16 , wherein the cancer cell expressing EGFR, c-Met, or EGFR and c-Met is derived from non-small cell lung cancer (NSCLC).

29. A method of inducing trogocytosis from a donor cancer cell that expresses EGFR, c-Met, or EGFR and c-Met to an acceptor macrophage cell or an acceptor monocyte cell, the method comprising contacting the donor cancer cell with a bispecific anti-EGFR/c-Met antibody for a time sufficient to induce trogocytosis from the donor cancer cell to the acceptor macrophage cell or the acceptor monocyte cell,

wherein the bispecific anti-EGFR/c-Met antibody comprises:

a first domain that binds EGFR, wherein the first domain comprises a VH comprising the amino acid sequence of SEQ ID NO: 13 and a VL comprising the amino acid sequence of SEQ ID NO: 14; and a second domain that binds c-Met, wherein the second domain comprises a VH comprising the amino acid sequence of SEQ ID NO: 15 and a VL comprising the amino acid sequence of SEQ ID NO: 16.

30. The method of claim 29 , wherein the bispecific anti-EGFR/c-Met antibody is an IgG1 isotype.

31. The method of claim 29 , wherein the acceptor cell is the macrophage cell.

32. The method of claim 29 , wherein the acceptor cell is the monocyte cell.

33. The method of claim 29 , wherein the donor cancer cell has a wild-type EGFR, an EGFR activating mutation, an EGFR gene amplification, increased levels of circulating HGF, a wild-type c-Met, a c-Met activating mutation, a c-Met gene amplification, or a mutant KRAS.

34. The method of claim 29 , wherein the EGFR activating mutation comprises a L718Q, G719A, G719X (X being any amino acid), L861X (X being any amino acid), L858R, E746K, L747S, E749Q, A750P, A755V, V765M, C797S, L858P, or T790M substitution, deletion of E746-A750, deletion of R748-P753, insertion of Ala (A) between M766 and A767, insertion of Ser, Val, and Ala (SVA) between S768 and V769, insertion of Asn and Ser (NS) between P772 and H773, insertion of one or more amino acids between D761 and E762, A763 and Y764, Y764 and Y765, M766 and A767, A767 and V768, S768 and V769, V769 and D770, D770 and N771, N771 and P772, P772 and H773, H773 and V774, V774 and C775, one or more deletions in EGFR exon 20, one or more insertions in EGFR exon 20, or any combination thereof.

35. The method of claim 34 , wherein the EGFR activating mutation comprises one or more insertions in EGFR exon 20.

36. The method of claim 34 , wherein the EGFR activating mutation comprises L858R, deletion of E746-A750, or deletion of R748-P753.

37. The method of claim 36 , wherein the EGFR activating mutation comprises L858R.

38. The method of claim 36 , wherein the EGFR activating mutation comprises deletion of E746-A750, or deletion of R748-P753.

39. The method of claim 33 , wherein the mutant KRAS comprises a G12V, G12C, or G12A substitution.

40. The method of claim 29 , wherein the contacting step is done in vitro.

41. The method of claim 29 , wherein the contacting step comprises administering the bispecific anti-EGFR/c-Met antibody to a subject.

42. The method of claim 41 , wherein the subject has an EGFR, c-Met, or EGFR and c-Met expressing cancer.

43. The method of claim 41 , wherein the subject has a newly diagnosed EGFR, c-Met, or EGFR and c-Met expressing cancer.

44. The method of claim 41 , wherein the subject is resistant or has acquired resistance to treatment with a prior anti-cancer therapy.

45. The method of claim 44 , wherein the prior anti-cancer therapy is a chemotherapy, a targeted anti-cancer therapy, or a kinase inhibitor.

46. The method of claim 45 , wherein the kinase inhibitor is an inhibitor of EGFR, c-Met, HER2, HER3, HER4, VEGFR, or AXL.

47. The method of claim 46 , wherein the kinase inhibitor is erlotinib, gefitinib, lapatinib, vandetanib, afatinib, osimertinib, lazertinib, poziotinib, criotinib, cabozantinib, capmatinib, axitinib, lenvatinib, nintedanib, regorafenib, pazopanib, sorafenib, or sunitinib.

48. The method of claim 42 , wherein the cancer cell expressing EGFR, c-Met, or EGFR and c-Met is derived from epithelial cell cancer, breast cancer, ovarian cancer, lung cancer, non-small cell lung cancer (NSCLC), lung adenocarcinoma, small cell lung cancer, colorectal cancer, anal cancer, prostate cancer, kidney cancer, bladder cancer, head and neck cancer, pharynx cancer, cancer of the nose, pancreatic cancer, skin cancer, oral cancer, cancer of the tongue, esophageal cancer, vaginal cancer, cervical cancer, cancer of the spleen, testicular cancer, gastric cancer, cancer of the thymus, colon cancer, thyroid cancer, liver cancer, HCC, or sporadic or hereditary papillary renal cell carcinoma PRCC.

49. The method of claim 48 , wherein the cancer cell expressing EGFR, c-Met, or EGFR and c-Met is derived from non-small cell lung cancer (NSCLC).

50. The method of claim 48 , comprising further administering one or more anti-cancer therapies to the subject.

51. The method of claim 50 , wherein the one or more anti-cancer therapies comprise a chemotherapy, a targeted anti-cancer therapy, or a kinase inhibitor.

52. The method of claim 51 , wherein the kinase inhibitor is an inhibitor of EGFR, c-Met, HER2, HER3, HER4, VEGFR, or AXL.

53. The method of claim 52 , wherein the kinase inhibitor is erlotinib, gefitinib, lapatinib, vandetanib, afatinib, osimertinib, lazertinib, poziotinib, criotinib, cabozantinib, capmatinib, axitinib, lenvatinib, nintedanib, regorafenib, pazopanib, sorafenib, or sunitinib.

54. The method of claim 53 , wherein the kinase inhibitor is lazertinib.

55. A method of inducing trogocytosis from a donor cancer cell that expresses EGFR, c-Met, or EGFR and c-Met to an acceptor macrophage cell or an acceptor monocyte cell, the method comprising contacting the donor cancer cell with a bispecific anti-EGFR/c-Met antibody for a time sufficient to induce trogocytosis from the donor cancer cell to the acceptor macrophage cell or the acceptor monocyte cell,

wherein the bispecific anti-EGFR/c-Met antibody comprises:

a HC1 comprising the amino acid sequence of SEQ ID NO: 17, a LC1 comprising the amino acid sequence of SEQ ID NO: 18, a HC2 comprising the amino acid sequence of SEQ ID NO: 19, and a LC2 comprising the amino acid sequence of SEQ ID NO: 20.

56. The method of claim 55 , wherein the bispecific anti-EGFR/c-Met antibody is an IgG1 isotype.

57. The method of claim 55 , wherein the acceptor cell is the macrophage cell.

58. The method of claim 55 , wherein the acceptor cell is the monocyte cell.

59. The method of claim 55 , wherein the donor cancer cell has a wild-type EGFR, an EGFR activating mutation, an EGFR gene amplification, increased levels of circulating HGF, a wild-type c-Met, a c-Met activating mutation, a c-Met gene amplification, or a mutant KRAS.

60. The method of claim 55 , wherein the EGFR activating mutation comprises a L718Q, G719A, G719X (X being any amino acid), L861X (X being any amino acid), L858R, E746K, L747S, E749Q, A750P, A755V, V765M, C797S, L858P, or T790M substitution, deletion of E746-A750, deletion of R748-P753, insertion of Ala (A) between M766 and A767, insertion of Ser, Val, and Ala (SVA) between S768 and V769, insertion of Asn and Ser (NS) between P772 and H773, insertion of one or more amino acids between D761 and E762, A763 and Y764, Y764 and Y765, M766 and A767, A767 and V768, S768 and V769, V769 and D770, D770 and N771, N771 and P772, P772 and H773, H773 and V774, V774 and C775, one or more deletions in EGFR exon 20, one or more insertions in EGFR exon 20, or any combination thereof.

61. The method of claim 60 , wherein the EGFR activating mutation comprises one or more insertions in EGFR exon 20.

62. The method of claim 60 , wherein the EGFR activating mutation comprises L858R, deletion of E746-A750, or deletion of R748-P753.

63. The method of claim 62 , wherein the EGFR activating mutation comprises L858R.

64. The method of claim 62 , wherein the EGFR activating mutation comprises deletion of E746-A750, or deletion of R748-P753.

65. The method of claim 59 , wherein the mutant KRAS comprises a G12V, G12C, or G12A substitution.

66. The method of claim 55 , wherein the contacting step is done in vitro.

67. The method of claim 55 , wherein the contacting step comprises administering the bispecific anti-EGFR/c-Met antibody to a subject.

68. The method of claim 67 , wherein the subject has an EGFR, c-Met, or EGFR and c-Met expressing cancer.

69. The method of claim 67 , wherein the subject has a newly diagnosed EGFR, c-Met, or EGFR and c-Met expressing cancer.

70. The method of claim 67 , wherein the subject is resistant or has acquired resistance to treatment with a prior anti-cancer therapy.

71. The method of claim 70 , wherein the prior anti-cancer therapy is a chemotherapy, a targeted anti-cancer therapy, or a kinase inhibitor.

72. The method of claim 71 , wherein the kinase inhibitor is an inhibitor of EGFR, c-Met, HER2, HER3, HER4, VEGFR, or AXL.

73. The method of claim 72 , wherein the kinase inhibitor is erlotinib, gefitinib, lapatinib, vandetanib, afatinib, osimertinib, lazertinib, poziotinib, criotinib, cabozantinib, capmatinib, axitinib, lenvatinib, nintedanib, regorafenib, pazopanib, sorafenib, or sunitinib.

74. The method of claim 69 , wherein the cancer cell expressing EGFR, c-Met, or EGFR and c-Met is derived from epithelial cell cancer, breast cancer, ovarian cancer, lung cancer, non-small cell lung cancer (NSCLC), lung adenocarcinoma, small cell lung cancer, colorectal cancer, anal cancer, prostate cancer, kidney cancer, bladder cancer, head and neck cancer, pharynx cancer, cancer of the nose, pancreatic cancer, skin cancer, oral cancer, cancer of the tongue, esophageal cancer, vaginal cancer, cervical cancer, cancer of the spleen, testicular cancer, gastric cancer, cancer of the thymus, colon cancer, thyroid cancer, liver cancer, HCC, or sporadic or hereditary papillary renal cell carcinoma PRCC.

75. The method of claim 74 , wherein the cancer cell expressing EGFR, c-Met, or EGFR and c-Met is derived from non-small cell lung cancer (NSCLC).

76. The method of claim 74 , comprising further administering one or more anti-cancer therapies to the subject.

77. The method of claim 76 , wherein the one or more anti-cancer therapies comprise a chemotherapy, a targeted anti-cancer therapy, or a kinase inhibitor.

78. The method of claim 77 , wherein the kinase inhibitor is an inhibitor of EGFR, c-Met, HER2, HER3, HER4, VEGFR, or AXL.

79. The method of claim 78 , wherein the kinase inhibitor is erlotinib, gefitinib, lapatinib, vandetanib, afatinib, osimertinib, lazertinib, poziotinib, criotinib, cabozantinib, capmatinib, axitinib, lenvatinib, nintedanib, regorafenib, pazopanib, sorafenib, or sunitinib.

80. The method of claim 79 , wherein the kinase inhibitor is lazertinib.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 3, 2022
From: MOORES, SHERI; VIJAYARAGHAVAN, SMRUTHI
To: JANSSEN BIOTECH, INC.
Reel/Frame 060713/0277 →
Continuity (4)
Division 16798662 · Feb 24, 2020
Provisional Application 62930190 · Nov 4, 2019
Provisional Application 62810716 · Feb 26, 2019
Related Publication 20230130600A1 · Apr 27, 2023
References Cited (162)
US 7615529B2 · Kong-Beltran et al. · 2009 [cited by applicant]
US 7767792B2 · Johns et al. · 2010 [cited by applicant]
US 7892770B2 · Cao et al. · 2011 [cited by applicant]
US 7981605B2 · Freeman et al. · 2011 [cited by applicant]
US 8067175B2 · Varmus et al. · 2011 [cited by applicant]
US 8242247B2 · Klein et al. · 2012 [cited by applicant]
US 8323962B2 · Dall'Acqua et al. · 2012 [cited by applicant]
US 8501171B2 · Bourel et al. · 2013 [cited by applicant]
US 8536118B2 · Kong-Beltran et al. · 2013 [cited by applicant]
US 8562985B2 · Michaud et al. · 2013 [cited by applicant]
US 8652473B2 · Johns et al. · 2014 [cited by applicant]
US 8715665B2 · Janne et al. · 2014 [cited by applicant]
US 8821869B2 · Michaud et al. · 2014 [cited by applicant]
US 8962808B2 · Chan et al. · 2015 [cited by applicant]
US 9394367B2 · Cheong et al. · 2016 [cited by applicant]
US 9580508B2 · Chiu et al. · 2017 [cited by applicant]
US 9593098B2 · Suh et al. · 2017 [cited by applicant]
US 9593164B2 · Chiu et al. · 2017 [cited by applicant]
US 9683052B2 · Blein et al. · 2017 [cited by applicant]
US 9683053B2 · Blein et al. · 2017 [cited by applicant]
US 10626189B2 · Giese et al. · 2020 [cited by applicant]
US 10813933B2 · Katayama et al. · 2020 [cited by applicant]
US 11459391B2 · Moores et al. · 2022 [cited by applicant]
US 20050272083A1 · Seshagiri · 2005 [cited by applicant]
US 20070287170A1 · Davis et al. · 2007 [cited by applicant]
US 20090182127A1 · Kjaergaard et al. · 2009 [cited by applicant]
US 20090226455A1 · Filvaroff · 2009 [cited by applicant]
US 20100015133A1 · Igawa et al. · 2010 [cited by applicant]
US 20100028637A1 · Tavsanli et al. · 2010 [cited by applicant]
US 20100286374A1 · Kannan et al. · 2010 [cited by applicant]
US 20110123532A1 · Gurney et al. · 2011 [cited by applicant]
US 20120149876A1 · Von Kreudenstein et al. · 2012 [cited by applicant]
US 20130195849A1 · Von Kreudenstein et al. · 2013 [cited by applicant]
US 20140141000A1 · Chiu et al. · 2014 [cited by applicant]
US 20140255408A1 · Chiu et al. · 2014 [cited by applicant]
US 20170073414A1 · Weiskopf et al. · 2017 [cited by applicant]
US 20170275367A1 · Chiu et al. · 2017 [cited by applicant]
US 20180312604A1 · Throsby et al. · 2018 [cited by applicant]
US 20190248907A1 · Doerner et al. · 2019 [cited by applicant]
US 20190315873A1 · Michieli · 2019 [cited by applicant]
US 20190046641A1 · Patel et al. · 2019 [cited by applicant]
US 20200087405A1 · Sidhu et al. · 2020 [cited by applicant]
US 20200239595A1 · Allison et al. · 2020 [cited by applicant]
US 20200270351A1 · Moores et al. · 2020 [cited by applicant]
US 20200316071A1 · Robichaux et al. · 2020 [cited by applicant]
US 20200317792A1 · Griswold et al. · 2020 [cited by applicant]
US 20200325243A1 · Tikhomirov et al. · 2020 [cited by applicant]
US 20200360394A1 · Oh et al. · 2020 [cited by applicant]
US 20210017285A1 · Laquerre et al. · 2021 [cited by applicant]
US 20220041704A1 · D'Hondt et al. · 2022 [cited by applicant]
US 20220372581A1 · Curtin · 2022 [cited by applicant]
CN 104955838A · 2015 [cited by applicant]
CN 107949401A · 2018 [cited by applicant]
EP 1868648B1 · 2015 [cited by applicant]
EP 1851339B1 · 2016 [cited by applicant]
EP 3611273A1 · 2020 [cited by applicant]
WO WO1988001649A1 · 1988 [cited by applicant]
WO WO1992001047A1 · 1992 [cited by applicant]
WO WO1994013804A1 · 1994 [cited by applicant]
WO WO1998044001A1 · 1998 [cited by applicant]
WO WO2006028936A2 · 2006 [cited by applicant]
WO WO2006028936A3 · 2006 [cited by applicant]
WO WO2008077546A1 · 2008 [cited by applicant]
WO WO2009018386A1 · 2009 [cited by applicant]
WO WO2009080251A1 · 2009 [cited by applicant]
WO WO2009080252A1 · 2009 [cited by applicant]
WO WO2009080254A1 · 2009 [cited by applicant]
WO WO2009085462A1 · 2009 [cited by applicant]
WO WO2011131746A2 · 2011 [cited by applicant]
WO WO2011131746A3 · 2011 [cited by applicant]
WO WO2015043614A1 · 2015 [cited by applicant]
WO WO2015188777A1 · 2015 [cited by applicant]
WO WO2016081423A1 · 2016 [cited by applicant]
WO 2016090174A1 · 2016 [cited by applicant]
WO WO2018094225A1 · 2018 [cited by applicant]
WO WO2018194356A1 · 2018 [cited by applicant]
WO WO2020055643A2 · 2020 [cited by applicant]
WO WO2020055643A3 · 2020 [cited by applicant]
WO WO2020205521A1 · 2020 [cited by applicant]
WO WO2020214824A1 · 2020 [cited by applicant]
WO WO2020214831A1 · 2020 [cited by applicant]
WO WO2020230091A1 · 2020 [cited by applicant]
Cho et al., 2018, “Poster #356: YH25448, a 3rd generation EGFR-TKI, in patients with EGFR-TK1-resistant NSCLC: Phase I/II study results,” American Society of Clinical Oncology (ASCO) Annual Meeting, Jun. 1-5, 2018 (5 pa… [cited by applicant]
Cho et al., 2018, “YH25448, a 3rd generation EGFR-TKI, in patients with EGFR-TK1-resistant NSCLC: Phase I/II study results,” American Society of Clinical Oncology (ASCO) Annual Meeting, Jun. 3, 2018, Abstract (2 pages). [cited by applicant]
ClinicalTrials.gov archive, “Study NCT03046992: A Phase I/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of YH25448 in Patients With EGFR Mutation Positi… [cited by applicant]
ClinicalTrials.gov archive, “Study NCT03046992: A Phase I/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of YH25448 in Patients With EGFR Mutation Positi… [cited by applicant]
ClinicalTrials.gov archive, “Study NCT03046992: A Phase I/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of YH25448 in Patients With EGFR Mutation Positi… [cited by applicant]
ClinicalTrials.gov archive, “Study NCT03046992: A Phase I/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of YH25448 in Patients With EGFR Mutation Positi… [cited by applicant]
ClinicalTrials.gov archive, “Study NCT03046992: A Phase I/II, Open-Label, Multicenter Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Anti-Tumor Activity of YH25448 in Patients With EGFR Mutation Positi… [cited by applicant]
Genosco, 2018, “Abstract 9033: Genosco/Yuhan Announce Results from Phase 1/2 Study of Lazertinib (YH25448, GNS-1480), a 3rd-Generation EGFR-TKI, in Advanced NSCLC,” American Society of Clinical Oncology (ASCO) Annual Me… [cited by applicant]
Shields et al., 2001, “High resolution mapping of the binding site on human IgG1 for Fc gamma RI, Fc gamma RII, Fc gamma RIII, and FcRn and design of IgG1 variants with improved binding to the Fc gamma R,” J. Biol. Chem… [cited by applicant]
Yun et al., 2019, “YH25448, an Irreversible EGFR-TKI with Potent Intracranial Activity in EGFR Mutant Non-Small Cell Lung Cancer,” Clin. Cancer Res., 25(8):2575-2587. [cited by applicant]
Weiskopf et al., 2015, “Macrophages are critical effectors of antibody therapies for cancer,” MAbs, 7(2):303-310. [cited by applicant]
Almatroodi et al., 2016, “Characterization of M1/M2 Tumour-Associated Macrophages (TAMs) and Th1/Th2 Cytokine Profiles in Patients with NSCLC,” Cancer Microenviron, 9(1):1-11 (Epub 2015). [cited by applicant]
Arenberg et al., 2000, “Macrophage infiltration in human non-small-cell lung cancer: the role of CC chemokines,” Cancer Immunol. Immunother., 49(2):63-70. [cited by applicant]
Arend et al., 2000, “Biological role of interleukin 1 receptor antagonist isoforms,” Ann. Rheum. Dis., 59 Suppl 1(Suppl 1):160-64. [cited by applicant]
Balkwill, 2004, “Cancer and the chemokine network,” Nat. Rev. Cancer, 4(7):540-550. [cited by applicant]
Bean et al., 2007, “MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib,” Proc. Natl. Acad. Sci. USA, 104(52):20932-20937. [cited by applicant]
Cappuzzo et al., 2005, “Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer,” J. Natl. Cancer Inst., 97(9):643-655. [cited by applicant]
Chen et al., 2009, “Clinicopathologic and molecular features of epidermal growth factor receptor T790M mutation and c-MET amplification in tyrosine kinase inhibitor-resistant Chinese non-small cell lung cancer,” Pathol.… [cited by applicant]
Cho et al., 2018 “Abstract MA26.09: Lazertinib, a 3rd Generation EGFR-TKI, in Patients with EGFR-TKI-Resistant NSCLC: Updated Results of a Phase I/II Study,” Journal of Thoracic Oncology, 13(10S):S453. [cited by applicant]
Chothia et al., 1987, “Canonical structures for the hypervariable regions of immunoglobulins,” J. Mol. Biol., 196(4):901-917. [cited by applicant]
Eisenhauer et al., 2009, “New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1),” Eur. J. Cancer, 45(2):228-247. [cited by applicant]
Engelman et al., 2007, “MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling,” Science, 316(5827):1039-1043. [cited by applicant]
Ferrara et al., 2006, “Modulation of therapeutic antibody effector functions by glycosylation engineering: influence of Golgi enzyme localization domain and co-expression of heterologous beta1, 4-N-acetylglucosaminyltra… [cited by applicant]
Ferrara et al., 2006, “The carbohydrate at FegammaRIIIa Asn-162. An element required for high affinity binding to non-fucosylated IgG glycoforms” J. Biol. Chem., 281(8):5032-5036 (Epub 2005). [cited by applicant]
GenBank Accession No. NP_001120972.1, “hepatocyte growth factor receptor isoform a preproprotein [ [cited by applicant]
GenBank Accession No. NP_005219.2, “epidermal growth factor receptor isoform a precursor [ [cited by applicant]
Graves et al., 1995, “Chemokines, a family of chemotactic cytokines,” Crit. Rev. Oral Biol. Med., 6(2):109-118. [cited by applicant]
Grugan et al., 2017, “Fc-mediated activity of EGFR x c-Met bispecific antibody JNJ-61186372 enhanced killing of lung cancer cells,” MAbs, 9(1):114-126 (Epub 2016). [cited by applicant]
Hardbower et al., 2017, “EGFR-mediated macrophage activation promotes colitis-associated tumorigenesis,” Oncogene., 36(27):3807-3819. [cited by applicant]
Honegger et al., 2001, “Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool,” J. Mol. Biol., 309(3):657-670. [cited by applicant]
Hong et al., 2017, “P3.02b-119: YH25448, a Highly Selective 3rd Generation EGFR TKI, Exhibits Superior Survival over Osimertinib in Animal Model with Brain Metastases from NSCLC,” Journal of Thoracic Oncology, 12(1S):S1… [cited by applicant]
Hynes et al., 2005, “ERBB receptors and cancer: the complexity of targeted inhibitors,” Nat. Rev. Cancer, 5(5):341-354. [cited by applicant]
International Search Report and Written Opinion for International Patent Application No. PCT/IB2020/051559 (Pub No. WO 2020174370) mailed Oct. 6, 2020 (16 pages). [cited by applicant]
International Search Report and Written Opinion for International Patent Application No. PCT/IB2020/054594 (Pub No. WO 2020230091) mailed Sep. 4, 2020 (11 pages). [cited by applicant]
Janne et al., 2006, “Effect of epidermal growth factor receptor tyrosine kinase domain mutations on the outcome of patients with non-small cell lung cancer treated with epidermal growth factor receptor tyrosine kinase i… [cited by applicant]
Janson et al., 1991, “Production of IL-1 receptor antagonist by human in vitro-derived macrophages. Effects of lipopolysaccharide and granulocyte-macrophage colony-stimulating factor,” J. Immunol., 147(12):4218-4223. [cited by applicant]
Jeffers et al., 1996, “Hepatocyte growth factor/scatter factor-Met signaling in tumorigenicity and invasion/metastasis,” J. Mol. Med. (Berl), 74(9):505-513. [cited by applicant]
Jia et al., 2008, “Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection,” J. Immunol., 180(10):6846-6853. [cited by applicant]
Kinder et al., 2015, “An Fc engineering approach that modulates antibody-dependent cytokine release without altering cell-killing functions,” MAbs, 7(3):494-504. [cited by applicant]
Knappik et al., 2000, “Fully synthetic human combinatorial antibody libraries (HuCAL) based on modular consensus frameworks and CDRs randomized with trinucleotides,” J. Mol. Biol., 296(1):57-86. [cited by applicant]
Kobayashi et al., 2005, “EGFR mutation and resistance of non-small-cell lung cancer to gefitinib,” N. Engl. J. Med., 352(8):786-792. [cited by applicant]
Konno et al., 2012, “Fucose content of monoclonal antibodies can be controlled by culture medium osmolality for high antibody-dependent cellular cytotoxicity,” Cytotechnology, 64(3):249-265 (Epub 2011). [cited by applicant]
Lefranc et al., 2003, “IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains,” Dev. Comp. Immunol., 27(1):55-77. [cited by applicant]
Loetscher et al., 1994, “Monocyte chemotactic proteins MCP-1, MCP-2, and MCP-3 are major attractants for human CD4+ and CD8+ T lymphocytes,” FASEB J., 8(13):1055-1060. [cited by applicant]
Martin et al., 1996, “Structural families in loops of homologous proteins: automatic classification, modelling and application to antibodies,” J. Mol. Biol., 263(5):800-815. [cited by applicant]
Martinelli et al., 2009, “Anti-epidermal growth factor receptor monoclonal antibodies in cancer therapy,” Clin. Exp. Immunol., 158(1):1-9. [cited by applicant]
Metlung et al., 2018, “Neutrophils Kill Antibody-Opsonized Cancer Cells by Trogoptosis,” Cell Rep., 23(13):3946-3959.e1-e6. [cited by applicant]
Moores et al., 2016, “A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors,” Cancer Res., 76(13):3942-3953. [cited by applicant]
Mori et al., 2004, “Engineering Chinese hamster ovary cells to maximize effector function of produced antibodies using FUT8 siRNA,” Biotechnol. Bioeng., 88(7):901-908. [cited by applicant]
Nakata et al., 2012, “Recent understanding of the molecular mechanisms for the efficacy and resistance of EGF receptor-specific tyrosine kinase inhibitors in non-small cell lung cancer,” Expert Opin. Ther. Targets, 16(8… [cited by applicant]
Olivier et al., 2010, “EB66 cell line, a duck embryonic stem cell-derived substrate for the industrial production of therapeutic monoclonal antibodies with enhanced ADCC activity,” MAbs, 2(4):405-415. [cited by applicant]
Pao et al., 2005, “Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain,” PLoS Med., 2(3):e73 (11 pages). [cited by applicant]
Perez-Soler et al., 2004, “Determinants of tumor response and survival with erlotinib in patients with non--small-cell lung cancer,” J. Clin. Oncol., 22(16):3238-3247. [cited by applicant]
Pham et al., 2011, “Dynamics of macrophage trogocytosis of rituximab-coated B cells,” PLoS One, 6(1):e14498 (11 pages). [cited by applicant]
PubChem. CID 121269225, Aug. 6, 2016, pp. 1-19; retreived from the internet <URL:https://pubchem.ncbi.nim.nih.gov/compound/121269225>; p. 2, formula (19 pages). [cited by applicant]
Sequist et al., 2011, “Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors,” Sci. Transl. Med., 3(75):75ra26 (13 pages). [cited by applicant]
Shi et al., 2010, “De novo selection of high-affinity antibodies from synthetic fab libraries displayed on phage as pIX fusion proteins,” J. Mol. Biol., 397(2):385-396. [cited by applicant]
Shields et al., 2002, “Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity,” J. Biol. Chem., 277(30):26733-26740. [cited by applicant]
Shinkawa et al., 2003, “The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellul… [cited by applicant]
Taylor et al., 2015, “Fcγ-receptor-mediated trogocytosis impacts mAb-based therapies: historical precedence and recent developments,” Blood, 125(5):762-766 (Epub 2014). [cited by applicant]
Turke et al., 2010, “Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC,” Cancer Cell, 17(1):77-88. [cited by applicant]
U.S. National Library of Meicine, “Study of JNJ-61186372, a Human Bispecific EGFR and cMet Antibody, in Subjects With Advanced Non-Small Cell Lung Cancer,” Aug. 14, 2020, ClinicalTrials.gov Identifier: NCT02609776 (14 p… [cited by applicant]
Uguccioni et al., 1995, “Actions of the chemotactic cytokines MCP-1, MCP-2, MCP-3, RANTES, MIP-1 alpha and MIP-1 beta on human monocytes,” Eur. J. Immunol., 25(1):64-68. [cited by applicant]
Ullrich et al., 1984, “Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells,” Nature, 309(5967):418-425. [cited by applicant]
Velmurugan et al., 2016, “Macrophage-Mediated Trogocytosis Leads to Death of Antibody-Opsonized Tumor Cells,” Mol. Cancer Ther., 15(8):1879-1889. [cited by applicant]
Vijayaraghavan et al., 2020, “Amivantamab (JNJ-61186372), an Fc Enhanced EGFR/cMet Bispecific Antibody, Induces Receptor Downmodulation and Antitumor Activity by Monocyte/Macrophage Trogocytosis,” Mol. Cancer Ther., 19(… [cited by applicant]
Wu et al., 1970, “An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity,” J. Exp. Med., 132(2):211-250. [cited by applicant]
Yano et al., 2008, “Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations,” Cancer Res., 68(22):9479-9487. [cited by applicant]
Yun et al., 2008, “The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP,” Proc. Natl. Acad. Sci. USA, 105(6):2070-2075. [cited by applicant]
Zhou et al., 2008, “Development of a simple and rapid method for producing non-fucosylated oligomannose containing antibodies with increased effector function,” Biotechnol. Bioeng., 99(3):652-665. [cited by applicant]
U.S. Appl. No. 15/931,726, (filed May 14, 2020), 20210017285 (Jan. 21, 2021), Combination Therapies With Bispecific Anti-EGFR/C-MET Antibodies and Third Generation EGFR Tyrosine Kinase Inhibitors, Pending. [cited by applicant]
Fury et al., “A phase-I trial of the epidermal growth factor receptor directed bispecific antibody MDX-447 without and with recombinant human granulocyte-colony stimulating factor in patients with advanced solid tumors”… [cited by applicant]
Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, Md., 1991. [cited by applicant]
Lefranc et al., “IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains”, 2003, Development Comparative Immunology, 27, 55-77. [cited by applicant]
Moores et al., “A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors”, Cancer Research 76(13), 2016, 3942-3953. [cited by applicant]
Moores et al., A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors. Cancer Res. 76(13):3942-3953, Jul. 1, 2016. [cited by applicant]
Olivier et al., “EB66 cell line, a duck embryonic stem cell-derived substrate for the industrial production of therapeutic monoclonal antibodies with enhanced ADCC activity”, MAbs, 2:4, 405-415. [cited by applicant]
Shi et al., “Trastuzumab Triggers Phagocytic Killing of High HER2 Cancer Cells In Vitro and In Vivo by Interaction with Fey Receptors on Macrophages”, J Immunol., Mar. 20, 2015, vol. 194, pp. 4379-4386. [cited by applicant]
Ullrich et al., “Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells”, Nature 309: 1984, pp. 418-425. [cited by applicant]
Vicencio et al., “Osimertinib and anti-HER3 combination therapy engages immune dependent tumor toxicity via STING activation in trans”, Cell Death & Disease vol. 13, Article 274, Mar. 28, 2022, pp. 1-14. [cited by applicant]