Claims for Patent: 9,758,589

Summary for Patent: 9,758,589

Title:	Methods for enhancing anti-tumor antibody therapy
Abstract:	Methods are provided to enhance the efficacy of antibody therapy directed to tumor cells.
Inventor(s):	Kohrt; Holbrook (San Francisco, CA), Houot; Roch (Rennes, FR), Levy; Ronald (Stanford, CA), Alizadeh; Arash Ash (San Mateo, CA), Goldstein; Matthew J. (Hillsborough, CA), Torchia; James (Stanford, CA)
Assignee:	The Board of Trustees of the Leland Stanford Junior University (Stanford, CA)
Application Number:	14/542,233
Patent Claims:	1. A method of treating cancer, the method comprising: administering to a patient a composition comprising an agonistic antibody to CD137 which agonistic antibody is characterized as agonistic in that, when the NK cells with CD137 on their surface are contacted with the agonistic antibody, their ADCC is increased as compared with that observed absent such contact; the patient having received anti-tumor antibody therapy a period of time prior to the administering, such that the increase in expression of CD137 has occurred. 2. The method of claim 1, wherein the agonistic antibody is particularly characterized in that, when tumor cells coated with the anti-tumor antibody are contacted with NK cells in which CD137 is expressed on the surface together with the agonistic antibody, apoptosis of the tumor cells is increased relative to that observed in absence of the agonistic antibody. 3. The method of claim 2, wherein the increased apoptosis is evaluated by flow cytometry. 4. The method of claim 2, wherein the increased apoptosis is evaluated by apoptotic cell death. 5. The method of claim 1, wherein the agonistic antibody is particularly characterized in that, when tumor cells coated with the anti-tumor antibody are contacted with NK cells in which CD137 expressed on the surface together with the agonistic antibody, tumor growth is reduced relative to that observed in absence of the agonistic antibody. 6. The method of claim 5, wherein the tumor growth is determined by [.sup.3H]-thymidine incorporation, counting cell number over a period of time, or detecting and/or measuring a marker associated with the cancer of interest. 7. The method of claim 2, wherein the increased apoptosis is associated with a reduction in cancer cell population or tumor size. 8. The method of claim 1, wherein the agonistic antibody is specifically characterized in that, when NK cells in which CD137 is expressed on the surface are contacted with the agonistic antibody, cytokine release from the NK cells is increased relative to that observed in absence of the agonistic antibody. 9. The method of claim 1, wherein the antibody directed against a tumor antigen is directed against a specific cancer epitope, or combination of epitopes, that allows the targeting or depletion of cancer cell populations expressing said antigen. 10. The method of claim 1, wherein the antibody directed against a tumor antigen and/or the agonistic antibody is a monoclonal antibody. 11. The method of claim 10, wherein the agonistic antibody is a xenogeneic human antibody. 12. The method of claim 10, wherein the agonistic antibody is a humanized antibody. 13. The method of claim 10, wherein the agonistic antibody is a chimeric antibody. 14. The method of claim 1, further comprising a step of determining the level of CD137. 15. The method of claim 14, wherein the level of CD137 is determined prior to administering an antibody directed against a tumor antigen, and the increase in expression following administration of the antibody directed against a tumor antigen is determined. 16. The method of claim 14 wherein the step of determining the level of CD137 in the sample comprises: providing a patient sample; and determining the level of CD137 in the sample. 17. The method of claim 16, wherein the patient sample is a patient blood sample or cellular fraction thereof. 18. The method of claim 1, wherein the tumor is a B cell malignancy. 19. The method of claim 18, wherein the B cell malignancy is marginal zone lymphoma, Hodgkins lymphoma, non-Hodgkins lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, myelogenous leukemia, or chemotherapy-resistant hairy cell leukemia. 20. The method of claim 18, wherein the B cell malignancy is a CD20-positive tumor and the antibody directed against a tumor antigen is specific for CD20. 21. The method of claim 20, wherein the antibody specific for CD20 is Rituximab, Tositumomab, or Ibritumomab. 22. The method of claim 18, wherein the B cell malignancy is a CD52-positive B cell malignancy and the antibody directed against a tumor antigen is specific for CD52. 23. The method of claim 20, wherein the antibody specific for CD52 is Alemtuzumab. 24. The method of claim 1, wherein the tumor is a solid tumor. 25. The method of claim 24, wherein the solid tumor is a breast carcinoma, a squamous cell carcinoma, a colon cancer, a head and neck cancer, a lung cancer, a genitourinary cancer, a rectal cancer, a gastric cancer, or an esophageal cancer. 26. The method of claim 24, wherein the solid tumor is a HER2-positive tumor and the antibody selective for a cancer cell antigen is specific for HER2. 27. The method of claim 26, wherein the antibody specific for HER2 is Trastuzumab. 28. The method of claim 24, wherein the solid tumor is an EGFR-positive tumor and the antibody selective for a cancer cell antigen is specific for EGFR. 29. The method of claim 28, wherein the antibody specific for EGFR is Cetuximab. 30. The method of claim 24, wherein the solid tumor is a 17-1A antigen-positive solid tumor and the antibody selective for a cancer cell antigen is specific for 17-1A antigen. 31. The method of claim 30, wherein the antibody selective for 17-1A antigen is Edrecolomab. 32. The method of claim 1, wherein the tumor is a CD19-positive tumor and the antibody selective for a cancer cell antigen is specific for CD19. 33. The method of claim 1, wherein the tumor is a CD22-positive tumor and the antibody selective for a cancer cell antigen is specific for CD22. 34. In a method of treating cancer that comprises a step of administering anti-tumor antibody therapy, the improvement comprising: a period of time after the step of administering anti-tumor antibody therapy (the "first administering step"), performing a second administering step that comprises administering a composition comprising an agonistic antibody that targets CD137, the period of time being sufficient so that expression of CD137 has been increased on surfaces of NK cells at the time of the second administering step, so that ADCC is increased. 35. In a method of treating cancer that comprises a step of administering a composition comprising an agonistic antibody to CD137, the improvement comprising performing the step of administering on a patient who previously received anti-tumor antibody therapy, a period of time prior to the step of administering, which period of time is sufficient so that expression of CD137 has been increased on surfaces of NK cells in the patient relative to that observed prior to the anti-tumor antibody therapy, and ADCC is increased after the administering. 36. A method of enhancing the anti-tumor effect of an antibody directed against a tumor antigen in a patient, the method comprising sequential administration of the anti-tumor antibody and an agonistic antibody targeting CD137; the agonistic antibody being characterized as agonistic in that, when the NK cells with CD137 on their surface are contacted with the agonistic antibody, their ADCC is increased as compared with that observed absent such contact; and the agonistic antibody being administered a period of time after the administration of the anti-tumor antibody, the period of time being sufficiently long that increased expression of CD137 on the NK cells has occurred.

Details for Patent 9,758,589

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2039-02-26
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2039-02-26
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2039-02-26
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2039-02-26