Claims for Patent: 7,981,418

Summary for Patent: 7,981,418

Title:	Predicting response to a HER inhibitor
Abstract:	The present application describes the use of low HER3 as a selection criterion for treating patients with a HER inhibitor, such as pertuzumab. It also describes the use of high HER2:HER3 ratio as a selection criterion for treating cancer patients, such as ovarian cancer patients, with a HER inhibitor, such as pertuzumab. In addition, the application describes the use of high HER3 as a selection criterion for treating cancer patients with a chemotherapeutic agent, for instance gemcitabine.
Inventor(s):	Amler; Lukas C. (Foster City, CA), Birkner; Merrill (Menlo Park, CA), Lin; Chin-Yu (Redwood City, CA), Moecks; Joachim (Mannheim, DE), Strauss; Andreas (Penzberg, DE)
Assignee:	Genentech, Inc. (South San Francisco, CA) Hoffmann-La Roche Inc. (Nutley, NJ)
Application Number:	12/074,229
Patent Claims:	1. A method for treating a patient with ovarian, peritoneal, or fallopian tube cancer, comprising administering to the patient a therapeutically effective amount of a HER2 dimerization inhibitor antibody that binds to a heterodimeric binding site of HER2, wherein the patient's cancer has been determined to express HER3 at a level less than the median level for HER3 expression in the cancer type. 2. The method of claim 1 wherein the patient's cancer has been determined to express HER3 at a level which is less than the 25.sup.th percentile for HER3 expression in the cancer type. 3. The method of claim 1 or claim 2 wherein HER3 expression has been determined using polymerase chain reaction (PCR). 4. The method of claim 3 wherein the PCR is quantitative reverse transcription polymerase chain reaction (qRT-PCR). 5. The method of claim 1 wherein the antibody has been determined to bind to a junction between domains I, II and III of HER2 extracellular domain. 6. The method of claim 1 wherein the HER2 antibody comprises the variable light and variable heavy amino acid sequences in SEQ ID Nos. 3 and 4, respectively. 7. The method of claim 6 wherein the HER2 antibody is pertuzumab. 8. The method of claim 1 or claim 7 wherein the HER2 antibody is a naked antibody. 9. The method of claim 1 or claim 7 wherein the HER2 antibody is an intact antibody. 10. The method of claim 1 or claim 7 wherein the HER2 antibody is an antibody fragment comprising an antigen binding region. 11. The method of claim 1 or claim 7 wherein the cancer type is platinum-resistant. 12. The method of claim 1 or claim 7 wherein the cancer type is advanced, refractory, or recurrent ovarian cancer. 13. The method of claim 1 or claim 7 which extends progression free survival (PFS) in the patient. 14. The method of claim 1 or claim 7 which extends overall survival (OS) in the patient. 15. The method of claim 1 or claim 7 wherein the HER2 dimerization inhibitor antibody is administered as a single anti-tumor agent. 16. The method of claim 1 or claim 7 comprising administering a second therapeutic agent to the patient. 17. The method claim 16 wherein the second therapeutic agent is selected from the group consisting of chemotherapeutic agent, HER antibody, antibody directed against a tumor associated antigen, anti-hormonal compound, cardioprotectant, cytokine, EGFR-targeted drug, anti-angiogenic agent, tyrosine kinase inhibitor, COX inhibitor, non-steroidal anti-inflammatory drug, farnesyl transferase inhibitor, antibody that binds oncofetal protein CA 125, HER2 vaccine, HER targeting therapy, Raf or ras inhibitor, liposomal doxorubicin, topotecan, taxane, dual tyrosine kinase inhibitor, TLK286, EMD-7200, a medicament that treats nausea, a medicament that prevents or treats skin rash or standard acne therapy, a medicament that treats or prevents diarrhea, a body temperature-reducing medicament, and a hematopoietic growth factor. 18. The method of claim 17 wherein the second therapeutic agent is a chemotherapeutic agent. 19. The method of claim 18 wherein the chemotherapeutic agent is selected from the group consisting of gemcitabine, carboplatin, paclitaxel, docetaxel, topotecan, and liposomal doxorubicin. 20. The method of claim 18 wherein the chemotherapeutic agent is an antimetabolite. 21. The method of claim 20 wherein the antimetabolite chemotherapeutic agent is gemcitabine. 22. The method of claim 16 wherein the second therapeutic agent is trastuzumab, erlotinib, or bevacizumab. 23. The method of claim 1 or claim 7 wherein the patient's cancer expresses HER2:HER3 at a level which is greater than the 25.sup.th percentile for HER2:HER3 expression in the cancer type. 24. The method of claim 23 wherein the patient's cancer expresses HER2:HER3 at a level which is greater than the median level for HER2:HER3 expression in the cancer type. 25. The method of claim 24 wherein the patient's cancer expresses HER2:HER3 at a level which is greater than the 75.sup.th percentile for HER2:HER3 expression in the cancer type. 26. A method for treating a patient with ovarian, peritoneal, or fallopian tube cancer comprising administering a therapeutically effective amount of pertuzumab to the patient, wherein the patient's cancer expresses has been determined to express HER3 at a level less than the median level for HER3 expression in ovarian, peritoneal, or fallopian tube cancer. 27. The method of claim 26 wherein the patient's cancer has been determined to express HER3 at a level which is less than the 25.sup.th percentile for HER3 expression in ovarian, peritoneal, or fallopian tube cancer. 28. The method of claim 26 or claim 27 wherein HER3 expression has been determined using polymerase chain reaction (PCR). 29. The method of claim 28 wherein the PCR is quantitative reverse transcription polymerase chain reaction (qRT-PCR). 30. The method of claim 26 or claim 27 which extends progression free survival (PFS). 31. The method of claim 26 or claim 27 which extends overall survival (OS). 32. The method of claim 26 or claim 27 wherein the patient has ovarian cancer. 33. The method of claim 32 wherein the ovarian cancer is platinum-resistant ovarian cancer. 34. The method of claim 32 wherein the patient has advanced, refractory, or recurrent ovarian cancer. 35. The method of claim 26 or claim 27 further comprising administering a chemotherapeutic agent to the patient. 36. The method of claim 35 wherein the chemotherapeutic agent is selected from the group consisting of gemcitabine, carboplatin, paclitaxel, docetaxel, topotecan, and liposomal doxorubicin. 37. The method of claim 36 wherein the chemotherapeutic agent is an antimetabolite chemotherapeutic agent. 38. The method of claim 37 wherein the antimetabolite chemotherapeutic agent is gemcitabine. 39. The method of claim 26 or claim 27 wherein the patient's cancer expresses HER2:HER3 at a level which is greater than the 25.sup.th percentile for HER2:HER3 expression in the cancer type. 40. The method of claim 39 wherein the patient's cancer expresses HER2:HER3 at a level which is greater than the median level for HER2:HER3 expression in the cancer type. 41. The method of claim 40 wherein the patient's cancer expresses HER2:HER3 at a level which is greater than the 75.sup.th percentile for HER2:HER3 expression in ovarian, peritoneal, or fallopian tube cancer. 42. A method for treating a patient with a type of ovarian, peritoneal, or fallopian tube cancer, comprising administering a therapeutically effective amount of a HER2 dimerization inhibitor antibody that binds to a heterodimeric binding site of HER2 to the patient, wherein the patient's cancer has been determined to express HER2:HER3 at a level which is greater than the 25.sup.th percentile for HER2:HER3 expression in the cancer type. 43. The method of claim 42 wherein the patient's cancer has been determined to express HER2:HER3 at a level which is greater than the median level for HER2:HER3 expression in the cancer type. 44. The method of claim 43 wherein the patient's cancer has been determined to express HER2:HER3 at a level which is greater than the 75.sup.th percentile for HER2:HER3 expression in the cancer type. 45. The method of claim 42, 43 or 44 wherein HER2 and HER3 expression has been determined using polymerase chain reaction (PCR). 46. The method of claim 45 wherein the PCR is quantitative reverse transcription polymerase chain reaction (qRT-PCR). 47. The method of claim 42 wherein the HER2 antibody binds to a junction between domains I, II and III of HER2 extracellular domain. 48. The method of claim 47 wherein the HER2 antibody comprises the variable light and variable heavy amino acid sequences in SEQ ID Nos. 3 and 4, respectively. 49. The method of claim 48 wherein the HER2 antibody is pertuzumab. 50. The method of claim 42 or claim 49 wherein the HER2 antibody is a naked antibody. 51. The method of claim 42 or claim 49 wherein the HER2 antibody is an intact antibody. 52. The method of claim 42 or claim 49 wherein the HER2 antibody is an antibody fragment comprising an antigen binding region. 53. The method of claim 42 or claim 49 wherein the cancer type is platinum-resistant. 54. The method of claim 42 or claim 49 wherein the cancer type is advanced, refractory, or recurrent ovarian cancer. 55. The method of claim 42 or claim 49 which extends progression free survival (PFS) in the patient. 56. The method of claim 42 or claim 49 which extends overall survival (OS) in the patient. 57. The method of claim 42 or claim 49 wherein the HER2 dimerization inhibitor antibody is administered as a single anti-tumor agent. 58. The method of claim 42 or claim 49 comprising administering a second therapeutic agent to the patient. 59. The method claim 58 wherein the second therapeutic agent is selected from the group consisting of chemotherapeutic agent, HER antibody, antibody directed against a tumor associated antigen, anti-hormonal compound, cardioprotectant, cytokine, EGFR-targeted drug, anti-angiogenic agent, tyrosine kinase inhibitor, COX inhibitor, non-steroidal anti-inflammatory drug, farnesyl transferase inhibitor, antibody that binds oncofetal protein CA 125, HER2 vaccine, HER targeting therapy, Raf or ras inhibitor, liposomal doxorubicin, topotecan, taxane, dual tyrosine kinase inhibitor, TLK286, EMD-7200, a medicament that treats nausea, a medicament that prevents or treats skin rash or standard acne therapy, a medicament that treats or prevents diarrhea, a body temperature-reducing medicament, and a hematopoietic growth factor. 60. The method of claim 58 wherein the second therapeutic agent is a chemotherapeutic agent. 61. The method of claim 60 wherein the chemotherapeutic agent is selected from the group consisting of gemcitabine, carboplatin, paclitaxel, docetaxel, topotecan, and liposomal doxorubicin. 62. The method of claim 60 wherein the chemotherapeutic agent is an antimetabolite. 63. The method of claim 62 wherein the antimetabolite chemotherapeutic agent is gemcitabine. 64. The method of claim 58 wherein the second therapeutic agent is trastuzumab, erlotinib, or bevacizumab.

Details for Patent 7,981,418

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2027-03-02
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2027-03-02
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2027-03-02
Genentech, Inc.	PERJETA	pertuzumab	Injection	125409	06/08/2012		2027-03-02