Claims for Patent: 8,470,542

Summary for Patent: 8,470,542

Title:	Methods and assays for measuring p95 and/or p95 complexes in a sample and antibodies specific for p95
Abstract:	The invention provides methods of measuring and/or quantifying the presence and/or amount of p95 and/or p95 complex in a sample. The invention also provides antibodies specific for p95.
Inventor(s):	Sperinde; Jeff (El Granada, CA), Winslow; John William (El Granada, CA), Jin; Xueguang (Fremont, CA)
Assignee:	Laboratory Corporation of America Holdings (Burlington, NC)
Application Number:	12/629,037
Patent Claims:	1. A method for determining whether a subject with a Her-2 positive cancer is likely to respond to treatment with a Her-2 pathway targeted therapy, comprising the steps of: (a) measuring the amount of a p95Her-2 protein fragment having a first amino acid corresponding to methionine 611 of Her-2 protein in a biological sample of the subject's cancer using a p95Her-2-specific antibody raised against a peptide having a sequence as set forth in SEQ ID NO:5 and produced by a hybridoma cell line selected from the group consisting of hybridoma cell lines having ATCC accession number PTA-9738 (p95.D3.4), PTA-9739 (p95.D8.2), and PTA-9740 (p95.D9.1); (b) determining whether the amount of p95Her-2 in the subject's sample is below a p95Her-2 cutoff, wherein the p95Her-2 cutoff comprises at least one of (i) a level of p95Her-2 expression at least two-fold greater than control cancer cells lines having basal levels of p95Her-2 expression or (ii) a level of p95Her-2 expression corresponding to at least a top 30.sup.th-50.sup.th percentile of p95Her-2 expression in a reference cohort of subjects having the Her-2 positive cancer; and (c) indicating that the subject is more likely to respond to a Her-2 pathway targeted therapy targeted to the extracellular domain of Her-2 if the amount of p95Her-2 in the biological sample is below the p95Her-2 cutoff as compared to if the p95Her-2 in the biological sample is above the p95Her-2 cutoff. 2. The method of claim 1, wherein the p95Her-2-specific antibody comprises an antibody produced by hybridoma cell line having ATCC accession number PTA-9740 (p95.D9.1). 3. The method of claim 1, wherein the cancer comprises a carcinoma. 4. The method of claim 1, wherein the cancer comprises at least one of a bone cancer, a brain cancer, an endocrine system cancer, a gastrointestinal cancer, a gynecological cancer, an andrological cancer, a head and neck cancer, a respiratory cancer, a thyroid cancer, a urinary tract cancer, or a metastatic cancer. 5. The method of claim 1, wherein the subject's cancer is breast cancer. 6. The method of claim 5, wherein the subject's cancer is metastatic breast cancer. 7. The method of claim 1, wherein the control cancer cells comprise SKBR3 and/or MCF7. 8. The method of claim 1, wherein the Her-2 targeted therapy targeted to the extracellular domain of Her-2 comprises trastuzumab and/or pertuzumab. 9. The method of claim 1, wherein the Her-2 pathway targeted therapy comprises trastuzumab. 10. The method of claim 1, wherein the Her-2 pathway targeted therapy comprises trastuzumab as part of a combination therapy. 11. The method of claim 10, wherein the combination therapy further comprises at least one of cytarabine, melphalan, topotecan, fludarabine, etoposide, idarubicin, daunorubicin, mitoxantrone, cisplatin, paclitaxel, or cyclophosphamide. 12. The method of claim 1, wherein the sample comprises a tissue sample. 13. The method of claim 1, wherein the sample comprises a fixed tissue sample, a frozen tissue sample, or a tissue lysate. 14. The method of claim 1, wherein the sample comprises a biological fluid containing circulating tumor cells. 15. The method of claim 14, wherein the sample comprises blood, plasma, or lymph. 16. The method of claim 1, wherein the response to a Her-2 pathway targeted agent is measured as at least one of overall survival rate, time to progression, disease-free survival, progression-free survival, time to distant reoccurrence, hazard ratio, and/or objective tumor response or clinical benefit using the RECIST criteria. 17. The method of claim 1, wherein measuring the amount of p95Her-2 in the biological sample comprises using immunohistochemistry to quantitate the amount of p95Her-2 protein. 18. The method of claim 1, wherein step (a) of measuring the amount of p95Her-2 in the biological sample comprises the steps of: (i) contacting the biological sample with a p95Her-2 binding composition that specifically binds to p95Her-2 protein, wherein the p95Her-2 binding composition comprises a p95Her-2-specific antibody produced by a hybridoma cell line selected from the group consisting of hybridoma cell lines having ATCC accession number PTA-9738 (p95.D3.4), PTA-9739 (p95.D8.2), and PTA-9740 (p95.D9.1); (ii) contacting the p95Her-2 binding composition with a tagged binding composition, wherein the tagged binding composition comprises a molecular tag attached thereto via a cleavable linkage, and wherein the tagged binding composition specifically binds to the p95Her-2 binding composition; (iii) cleaving the cleavable linker of the tagged binding composition, thereby releasing the molecular tag; and (iv) quantitating the released molecular tag to determine the amount of p95Her-2 protein in the biological sample. 19. The method of claim 1, wherein the subject's cancer has been characterized as a Her-2 positive cancer based on the amount of Her-2 measured in the biological sample. 20. The method of claim 19, wherein measuring the amount of Her-2 in the biological sample comprises quantitation of Her-2 gene expression levels or Her-2 gene copy number. 21. The method of claim 19, wherein measuring the amount of Her-2 in the biological sample comprises using in situ hybridization, immunohistochemistry, quantitative mRNA analysis, or a hybridization array, to quantitate the amount of Her-2. 22. The method of claim 19, wherein measuring the amount of Her-2 in the biological sample comprises: a) contacting the biological sample with a Her-2-specific antibody; and b) quantitating the amount of the Her-2 specific antibody that binds to Her-2 in the biological sample. 23. The method of claim 19, wherein measuring the amount of Her-2 in the biological sample comprises measuring total Her-2 protein. 24. The method of claim 1, wherein the p95Her-2 cutoff comprises a level of p95Her-2 expression corresponding to at least a top 40.sup.th percentile of p95Her-2 expression in a reference cohort of subjects having the Her-2 positive cancer. 25. The method of claim 1, wherein the p95Her-2 cutoff comprises a level of p95Her-2 expression corresponding to at least a top 30.sup.th percentile of p95Her-2 expression in a reference cohort of subjects having the Her-2 positive cancer. 26. The method of claim 1, further comprising: (d) indicating that the subject is more likely to respond to a Her-2 pathway targeted therapy targeted to the intracellular domain of Her-2 if the amount of p95Her-2 in the biological sample is above the p95Her-2 cutoff as compared to a Her-2 pathway targeted therapy targeted to the extracellular domain of Her-2. 27. The method of claim 26, wherein the Her-2 pathway targeted agent targeted to the intracellular domain of Her-2 comprises a tyrosine kinase inhibitor. 28. The method of claim 26, wherein the Her-2 pathway targeted agent targeted to the intracellular domain of Her-2 comprises at least one of lapatinib, canertinib, mubritinib, AEE-788, HKI-272, BIBW-2992, or BMS-599626.

Details for Patent 8,470,542

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2028-12-01
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2028-12-01
Genentech, Inc.	PERJETA	pertuzumab	Injection	125409	06/08/2012		2028-12-01
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2028-12-01