Claims for Patent: 9,861,633

Summary for Patent: 9,861,633

Title:	Methods of treating urothelial carcinoma
Abstract:	Methods and compositions for treating a urothelial and/or a micropapillary carcinoma, such as a micropapillary urothelial carcinoma are disclosed.
Inventor(s):	Ali; Siraj Mahamed (Cambridge, MA), Hawryluk; Matthew J. (Watertown, MA), Ross; Jeffrey S. (Lebanon Springs, NY), Stephens; Philip James (Lexington, MA)
Assignee:	FOUNDATION MEDICINE, INC. (Cambridge, MA)
Application Number:	14/333,368
Patent Claims:	1. A method of treating a subject having a micropapillary urothelial or a bladder carcinoma that lacks HER2 gene amplification, comprising: (i) identifying the carcinoma as having a HER2 kinase activating mutation in the extracellular domain at residue 310 or at residue 157 of HER2; (ii) identifying the carcinoma as having a micropapillary histology; and (iii) administering to the subject an effective amount of an agent that inhibits HER2 expression or activity, thereby treating the carcinoma. 2. The method of claim 1, wherein the subject is a human. 3. The method of claim 1, wherein the subject does not have, or is identified as not having, an elevated level of a HER2 gene product. 4. The method of claim 1, wherein the HER2 kinase activating mutation is chosen from: (i) a substitution at residue 310 of HER2; (ii) a substitution of a serine residue at position 310 (S310) of HER2 to phenylalanine; (iii) a substitution of a serine residue at position 310 (S310) of HER2 to tyrosine; (iv) a substitution at residue 157; or (v) a substitution of an arginine residue at position 157 (R157) of HER2 to tryptophan. 5. The method of claim 1, wherein the subject is undergoing or has undergone a treatment with a non-HER2 therapeutic agent or therapeutic modality. 6. The method of claim 5, wherein the non-HER2 therapeutic agent or therapeutic modality comprises one or more of: methotrexate, vinblastine, doxorubicin, or cisplatin. 7. The method of claim 5, wherein, responsive to a determination of the presence of the HER2 kinase activating mutation, the non-HER2 therapeutic agent or therapeutic modality is discontinued. 8. The method of claim 5, wherein the agent that inhibits HER2 expression or activity is administered after cessation of the non-HER2 therapeutic agent or therapeutic modality. 9. The method of claim 1, wherein the agent that inhibits HER2 expression or activity is chosen from one or more of: a kinase inhibitor; a multi-specific kinase inhibitor; a HER2-specific inhibitor; an EGFR inhibitor; a reversible or an irreversible HER2 inhibitor; a pan ERBB inhibitor; a small molecule inhibitor that is selective for HER2; an antibody molecule; a monoclonal or a bispecific antibody against HER2; an antibody to HER2 conjugated to a cytotoxic agent; or a HER2 cellular immunotherapy. 10. The method of claim 1, wherein the agent that inhibits HER2 expression or activity is an anti-HER2 antibody molecule, or a conjugate thereof. 11. The method of claim 1, wherein the agent that inhibits HER2 expression or activity is chosen from one or more of: AV-203, AMG 888, U3-1287, APC8024, DN24-02, Neuvenge, Lapuleucel-T, MM-111, MM-121, SAR256212, MM-141, LJM716, REGN1400, MEHD7945A, RG7597, RG7116, Trastuzumab, trastuzumab emtansine (T-DM1), pertuzumab, afatinib, TAK-285, Neratinib, Dacomitinib, BMS-690514, BMS-599626, Pelitinib, CP-724714, Lapatinib, TAK-165, ARRY-380, AZD8931, or Neratinib. 12. The method of claim 1, wherein the HER2 comprises the amino acid sequence of SEQ ID NO: 1. 13. The method of claim 3, wherein the subject does not have an elevated level of a HER2 gene product. 14. The method of claim 3, wherein the subject is identified as not having an elevated level of a HER2 gene product. 15. The method of claim 4, wherein the HER2 kinase activating mutation is a substitution at residue 157 of HER2. 16. A method of treating a subject having a micropapillary carcinoma that lacks HER2 gene amplification, comprising administering to the subject an effective amount of an agent that inhibits HER2 expression or activity, wherein: (i) the carcinoma has a HER2 kinase activating mutation at residue 310 or residue 157 of HER2; and (ii) the carcinoma is chosen from a cancer of the urinary tract, bladder, or urothelial cells, thereby treating the carcinoma. 17. The method of claim 16, wherein the subject does not have a gene amplification or overexpression of HER2 or a HER2 gene product. 18. The method of claim 16, wherein the subject is identified as not having a gene amplification or overexpression of HER2 or a HER2 gene product. 19. The method of claim 16, wherein the subject does not have, or is identified as not having, an elevated level of a HER2 gene product. 20. The method of claim 16, wherein the subject is a human. 21. The method of claim 16, wherein the subject is undergoing or has undergone treatment with a non-HER2 therapeutic agent or therapeutic modality that comprises one or more of: methotrexate, vinblastine, doxorubicin, or cisplatin. 22. The method of claim 21, wherein, responsive to the determination of the presence of one or both of the HER2 kinase activating mutation or a micropapillary histology in the carcinoma, the non-HER2 therapeutic agent or therapeutic modality is discontinued. 23. The method of claim 21, wherein the agent that inhibits HER2 expression or activity is administered after cessation of the non-HER2 therapeutic agent or therapeutic modality. 24. The method of claim 16, wherein the agent that inhibits HER2 expression or activity is chosen from one or more of: a kinase inhibitor; a multi-specific kinase inhibitor; a HER2-specific inhibitor; an EGFR inhibitor; a reversible or an irreversible HER2 inhibitor; a pan ERBB inhibitor; a small molecule inhibitor that is selective for HER2; an antibody molecule; a monoclonal or a bispecific antibody against HER2; an antibody to HER2 conjugated to a cytotoxic agent; or a HER2 cellular immunotherapy. 25. The method of claim 16, wherein the agent that inhibits HER2 expression or activity is an anti-HER2 antibody molecule, or a conjugate thereof. 26. The method of claim 16, wherein the agent that inhibits HER2 expression or activity is chosen from one or more of: AV-203, AMG 888, U3-1287, APC8024, DN24-02, Neuvenge, Lapuleucel-T, MM-111, MM-121, SAR256212, MM-141, LJM716, REGN1400, MEHD7945A, RG7597, RG7116, Trastuzumab, trastuzumab emtansine (T-DM1), pertuzumab, afatinib, TAK-285, Neratinib, Dacomitinib, BMS-690514, BMS-599626, Pelitinib, CP-724714, Lapatinib, TAK-165, ARRY-380, AZD8931, or Neratinib. 27. The method of claim 16, wherein the agent that inhibits HER2 expression or activity is chosen from an antisense molecule, a ribozyme, a double stranded RNA, or a triple helix molecule, wherein the agent hybridizes to and/or inhibits a HER2 nucleic acid, or a transcription regulatory region that blocks or reduces mRNA expression of the nucleic acid encoding a HER2 gene product with a HER2 kinase activating mutation. 28. The method of claim 16, wherein the HER2 kinase activating mutation is detected by sequencing. 29. The method of claim 16, wherein the HER2 kinase activating mutation is detected in a nucleic acid molecule acquired from the subject, wherein said nucleic acid molecule is present in a circulating cell; a urothelial or micropapillary carcinoma; or a blood or plasma sample. 30. The method of claim 16, wherein the HER2 kinase activating mutation is chosen from: (i) a substitution at residue 310 of HER2; (ii) a substitution of a serine residue at position 310 (S310) of HER2 to phenylalanine or tyrosine of HER2; (iii) a substitution at residue 157 of HER2; or (iv) a substitution of an arginine residue at position 157 (R157) of HER2 to tryptophan, wherein the HER2 comprises the amino acid sequence of SEQ ID NO:1. 31. The method of claim 30, wherein the HER2 kinase activating mutation is a substitution of a serine residue at position 310 (S310) of HER2 to phenylalanine or tyrosine. 32. The method of claim 31, wherein the HER2 kinase activating mutation is detected by sequencing. 33. The method of claim 30, wherein the agent that inhibits HER2 expression or activity is administered responsive to a determination of the presence of the HER2 kinase activating mutation in the carcinoma. 34. The method of claim 30, wherein the HER2 kinase activating mutation is detected in a nucleic acid molecule acquired from the subject, wherein said nucleic acid molecule is present in a circulating cell, a urothelial or micropapillary carcinoma, or a blood or plasma sample. 35. The method of claim 30, wherein the HER2 kinase activating mutation is a substitution at residue 310 of HER2. 36. The method of claim 16, wherein the HER2 kinase activating mutation is a substitution at residue 310 of HER2. 37. The method of claim 16, wherein the HER2 kinase activating mutation is a substitution at residue 157 of HER2. 38. A method of treating a subject having a micropapillary carcinoma chosen from a cancer of the urinary tract, bladder, or urothelial cells, said method comprising: (i) identifying the carcinoma as having a HER2 kinase activating mutation in the extracellular domain at residue 310 or at residue 157 of HER2; and (ii) administering to the subject an effective amount of an agent that inhibits HER2, wherein the agent is chosen from one or more of a kinase inhibitor, an antibody molecule, or a HER2 cellular immunotherapy; and wherein the carcinoma does not have an elevated level of a HER2 gene product, thereby treating the micropapillary carcinoma. 39. The method of claim 38, wherein the agent that inhibits HER2 is chosen from one or more of: AV-203, AMG 888, U3-1287, APC8024, DN24-02, Neuvenge, Lapuleucel-T, MM-111, MM-121, SAR256212, MM-141, LJM716, REGN1400, MEHD7945A, RG7597, RG7116, Trastuzumab, trastuzumab emtansine (T-DM1), pertuzumab, afatinib, TAK-285, Neratinib, Dacomitinib, BMS-690514, BMS-599626, Pelitinib, CP-724714, Lapatinib, TAK-165, ARRY-380, AZD8931, or Neratinib. 40. The method of claim 38, wherein the HER2 kinase activating mutation is chosen from: (i) a substitution at residue 310 of HER2; (ii) a substitution of a serine residue at position 310 (S310) of HER2 to phenylalanine; (iii) a substitution of a serine residue at position 310 (S310) of HER2 to tyrosine; (iv) a substitution at residue 157 of HER2; or (v) a substitution of an arginine residue at position 157 (R157) of HER2 to tryptophan. 41. The method of claim 40, wherein the HER2 kinase activating mutation is a substitution at residue 310 of HER2. 42. The method of claim 41, wherein the HER2 kinase activating mutation is a substitution of residue 5310 of HER2 to phenylalanine or tyrosine. 43. The method of claim 40, wherein the HER2 comprises the amino acid sequence of SEQ ID NO: 1. 44. The method of claim 38, wherein the HER2 comprises the amino acid sequence of SEQ ID NO: 1. 45. The method of claim 38, wherein the agent that inhibits HER2 is an anti-HER2 antibody molecule, or a conjugate thereof. 46. The method of claim 38, wherein the subject is a human. 47. The method of claim 38, wherein the carcinoma is identified as not having an elevated level of a HER2 gene product. 48. The method of claim 47, wherein the carcinoma is identified as having a micropapillary histology. 49. The method of claim 40, wherein the HER2 kinase activating mutation is a substitution at residue 157 of HER2.

Details for Patent 9,861,633

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2033-07-17
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2033-07-17
Genentech, Inc.	PERJETA	pertuzumab	Injection	125409	06/08/2012		2033-07-17
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2033-07-17