Claims for Patent: 10,385,405

Summary for Patent: 10,385,405

Title:	Gene expression markers of tumor resistance to HER2 inhibitor treatment
Abstract:	The present invention concerns markers of resistance of HER2 expressing tumors to treatment with HER2 inhibitors, such as HER2 antibodies, including trastuzumab.
Inventor(s):	Lee-Hoeflich; Si Tuen (Millbrae, CA), Stern; Howard (San Carlos, CA)
Assignee:	Genentech, Inc. (South San Francisco, CA)
Application Number:	15/365,296
Patent Claims:	1. A method of increasing the likelihood of response of a mammalian subject diagnosed with a HER2 expressing tumor to treatment with a HER2 antibody binding to the 4D5 epitope of HER2, or an antigen-binding fragment thereof, comprising: (a) measuring in a tumor cell obtained from said mammalian subject, a lower expression level of the RNA transcript or expression product of a PTPN11 gene relative to the expression level of PTPN11 gene in a normal cell of the same cell type, wherein the identical or increased expression level identifies the subject as not likely to be resistant to treatment with said HER2 antibody or antigen-binding fragment, and (b) treating the subject with said HER2 antibody or antigen-binding fragment. 2. The method of claim 1 wherein the mammalian subject is a human patient. 3. The method of claim 2 wherein the tumor expresses HER2 at least at a 1+ level. 4. The method of claim 2 wherein the tumor expresses HER2 at least at a 2+ level. 5. The method of claim 2 wherein the tumor expresses HER at a 3+ level. 6. The method of claim 2 wherein the tumor is selected from the group consisting of breast cancer, squamous cell cancer, small-cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), adenocarcinoma of the lung and squamous carcinoma of the lung, cancer of the peritoneum, hepatocellular cancer, gastric or stomach cancer including gastrointestinal cancer, pancreatic cancer, glioblastoma, cervical cancer, ovarian cancer, liver cancer, bladder cancer, hepatoma, colon cancer, rectal cancer, colorectal cancer, endometrial or uterine carcinoma, salivary gland carcinoma, kidney or renal cancer, prostate cancer, vulval cancer, thyroid cancer, hepatic carcinoma, anal carcinoma, penile carcinoma, testicular cancer, esophageal cancer, tumors of the biliary tract, and head and neck cancer. 7. The method of claim 2 wherein the tumor is breast cancer. 8. The method of claim 7 wherein the tumor is metastatic breast cancer. 9. The method of claim 1 wherein the HER2 antibody or antigen-binding fragment is selected from the group consisting of humanized antibodies huMAb4D5-1, huMAb4D5-2, huMAb4D5-3, huMAb4D5-4, huMAb4D5-5, huMAb4D5-6, huMAb4D5-7 and trastuzumab, and fragments thereof. 10. The method of claim 9 wherein the HER2 antibody or antibody fragment is trastuzumab or an antigen-binding fragment thereof. 11. The method of claim 2 wherein the tumor cell is from a fixed, wax-embedded cancer tissue specimen of said patient. 12. The method of claim 2 wherein the tumor cell is from a core biopsy tissue. 13. The method of claim 1, wherein expression level of the RNA transcript or expression product of a PTPN11 gene in said tumor cell and said normal cell of the same cell type is determined using an apparatus adapted to determine the expression levels of said transcripts or their expression products. 14. The method of claim 13, wherein said determination of the expression levels is performed by using a software program executed by a suitable processor. 15. The method of claim 14, wherein the program is embodied in software stored on a tangible medium. 16. The method of claim 15, wherein the tangible medium is selected from the group consisting of a CD-ROM, a floppy disk, a hard drive, a DVD, and a memory associated with the processor.

Details for Patent 10,385,405

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2027-06-08
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2027-06-08
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2027-06-08