Anti-Ly6E antibodies and methods of use

Patent metadata

Field	Value
Publication number	US-10066022-B2
Application number	US-201615018710-A
Country	US
Kind code	B2
Filing date	Feb 8, 2016
Priority date	Oct 21, 2013
Publication date	Sep 4, 2018
Grant date	Sep 4, 2018

Abstract

The invention provides anti-Ly6E antibodies, immunoconjugates and methods of using the same. In some embodiments, the anti-Ly6E antibodies comprise heavy chain HVRs comprising the amino acid sequences of SEQ ID NOs: 32-34 and/or light chain HVRs comprising the amino acid sequences of SEQ ID NOs: 29-31.

First claim

The invention claimed is:

1. A method of identifying a human Ly6E-positive cancer in a patient, comprising contacting a cancer sample from the patient with an isolated antibody that binds to human Ly6E, wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:32, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:33, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:34, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:29, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:30, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:31, and detecting whether a complex is formed between the anti-Ly6E antibody and a human Ly6E in the cancer sample, wherein the cancer patient is identified as having a human Ly6E-positive cancer if a complex between the anti-Ly6E antibody and the human Ly6E in the cancer sample is detected, and wherein the method comprises a control.

2. The method of claim 1 , wherein the antibody that binds to human Ly6E is an antibody comprising (a) a VH sequence of SEQ ID NO:28; (b) a VL sequence of SEQ ID NO:27; or (c) a VH sequence of SEQ ID NO:28 and a VL sequence of SEQ ID NO:27.

3. The method of claim 1 , wherein the cancer sample is a breast cancer sample, a pancreatic cancer sample, a colon cancer sample, a colorectal cancer sample, a melanoma cancer sample, an ovarian cancer sample, a non-small cell lung cancer sample, an esophageal cancer sample, a head and neck cancer sample, a kidney cancer sample, a soft tissue cancer sample, an endometrial cancer sample, or a gastric cancer sample.

4. The method of claim 1 , wherein the anti-Ly6E antibody is an antibody comprising (a) a VH sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:28; (b) a VL sequence having at least 95% sequence identity to the amino acid sequence of SEQ ID NO:27; or (c) a VH sequence as in (a) and a VL sequence as in (b).

5. The method of claim 1 , wherein the anti-Ly6E antibody is a monoclonal antibody.

6. The method of claim 5 , wherein the anti-Ly6E antibody is a rabbit, humanized, or chimeric antibody.

7. The method of claim 5 , wherein the anti-Ly6E antibody is an IgG selected from IgG1, IgG2a, IgG2b, IgG3, and IgG4.

8. The method of claim 3 , wherein the cancer sample is a breast cancer sample from a Her2 positive breast cancer, a Her2 negative breast cancer, a Her2 negative/hormone receptor positive (Her2−/ER+/PR+) breast cancer, or a triple negative (Her2−/ER−/PR−) breast cancer.

9. The method of claim 3 , wherein the cancer sample is a gastric cancer sample from a Her2 positive gastric cancer or a Her2 negative gastric cancer.

10. The method of claim 6 , wherein the anti-Ly6E antibody is a rabbit antibody or chimeric antibody.

11. The method of claim 1 , wherein the antibody that binds to human Ly6E is an antibody comprising a VH sequence of SEQ ID NO:28 and a VL sequence of SEQ ID NO:27.

12. The method of claim 11 , wherein the cancer sample is a breast cancer sample, a pancreatic cancer sample, a colon cancer sample, a colorectal cancer sample, a melanoma cancer sample, an ovarian cancer sample, a non-small cell lung cancer sample, an esophageal cancer sample, a head and neck cancer sample, a kidney cancer sample, a soft tissue cancer sample, an endometrial cancer sample, or a gastric cancer sample.

13. The method of claim 12 , wherein the cancer sample is a breast cancer sample from a Her2 positive breast cancer, a Her2 negative breast cancer, a Her2 negative/hormone receptor positive (Her2−/ER+/PR+) breast cancer, or a triple negative (Her2−/ER−/PR−) breast cancer.

14. The method of claim 12 , wherein the cancer sample is a gastric cancer sample from a Her2 positive gastric cancer or a Her2 negative gastric cancer.

15. The method of claim 11 , wherein the anti-Ly6E antibody is a monoclonal antibody.

16. The method of claim 15 , wherein the anti-Ly6E antibody is an IgG selected from IgG1, IgG2a, IgG2b, IgG3, and IgG4.

17. The method of claim 15 , wherein the anti-Ly6E antibody is a rabbit antibody or chimeric antibody.

18. A method of treating a cancer patient having a human Ly6E-positive cancer comprising:
a) identifying the cancer patient as having a human Ly6E-positive cancer, comprising
i) contacting a cancer sample from the patient with an isolated antibody that binds to human Ly6E, wherein the antibody comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:32, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:33, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:34, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO:29, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:30, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:31, and
ii) detecting whether a complex is formed between the anti-Ly6E antibody and a human Ly6E in the cancer sample, wherein the cancer patient is identified as having a human Ly6E-positive cancer if a complex between the anti-Ly6E antibody and the human Ly6E in the cancer sample is detected, and wherein the identifying step comprises a control; and

b) administering an anti-Ly6E antibody immunoconjugate to the cancer patient, wherein the anti-Ly6E antibody immunoconjugate comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:10, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:11, (c) HVR-H3 comprising the amino acid sequence of SEQ ID NO:12, (d) HVR-L1 comprising the amino acid sequence of SEQ ID NO: 7, (e) HVR-L2 comprising the amino acid sequence of SEQ ID NO:8, and (f) HVR-L3 comprising the amino acid sequence of SEQ ID NO:9.

19. The method of claim 18 , wherein the human Ly6E-positive cancer is a Her2 positive breast cancer, a Her2 negative breast cancer, a Her2 negative/hormone receptor positive (Her2−/ER+/PR+) breast cancer, or a triple negative (Her2−/ER−/PR−) breast cancer.

20. The method of claim 18 , wherein the human Ly6E-positive cancer is a Her2 positive gastric cancer or a Her2 negative gastric cancer.

21. The method of claim 18 , wherein the human Ly6E-positive cancer is a Her2 positive breast cancer, a triple negative (Her2−/ER−/PR−) breast cancer, or a pancreatic cancer.

22. The method of claim 18 , wherein the anti-Ly6E antibody immunoconjugate comprises hu9B12 v12.

23. The method of claim 22 , wherein the human Ly6E-positive cancer is a Her2 positive breast cancer, a triple negative (Her2−/ER−/PR−) breast cancer, or a pancreatic cancer.

24. A method of treating a cancer patient having a human Ly6E-positive cancer comprising:
a) identifying the cancer patient as having a human Ly6E-positive cancer, comprising
i) contacting a cancer sample from the patient with an isolated antibody that binds to human Ly6E, wherein the antibody comprises a VH sequence of SEQ ID NO:28 and a VL sequence of SEQ ID NO: 27, and
ii) detecting whether a complex is formed between the anti-Ly6E antibody and a human Ly6E in the cancer sample, wherein the cancer patient is identified as having a human Ly6E-positive cancer if a complex between the anti-Ly6E antibody and the human Ly6E in the cancer sample is detected, and wherein the identifying step comprises a control; and

b) administering an anti-Ly6E antibody immunoconjugate to the cancer patient, wherein the anti-Ly6E antibody immunoconjugate comprises (a) HVR-H1 comprising the amino acid sequence of SEQ ID NO:10, (b) HVR-H2 comprising the amino acid sequence of SEQ ID NO:11, (c)

Assignees

• Genentech Inc

Inventors

• Asundi Jyoti
• Firestein Ron
• Polakis Paul
• Sakanaka Chie
• Chang Peter
• Venook Rayna Takaki

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• G01N33/57545 Primary

  of the ovaries · CPC title

• G01N33/57535

  of the large intestine, e.g. colon, rectum or anus · CPC title

• G01N33/57525

  of the liver or pancreas · CPC title

• G01N33/57515

  of the breast · CPC title