Claims for Patent: 9,913,901

Summary for Patent: 9,913,901

Title:	Combination therapy for treating HER2-positive cancers
Abstract:	Methods for treating cancer patients with HER2-positive tumors are disclosed. The methods comprise administering to a patient a therapeutically effective amount of a combination of (i) an anthracycline-loaded immunoliposome with a targeting moiety that is a first anti-HER2 antibody and (ii) an anti-cancer therapeutic comprising a second anti-HER2 antibody.
Inventor(s):	Moyo; Victor (Ringoes, NJ), Hendriks; Bart S. (Belmont, MA), Wickham; Thomas (Groton, MA), Geretti; Elena (Cambridge, MA), Reynolds; Joseph G. (North Andover, MA), Espelin; Christopher W. (Belmont, MA)
Assignee:	Merrimack Pharmaceuticals, Inc. (Cambridge, MA)
Application Number:	14/650,250
Patent Claims:	1. A method of treating a patient with gastric cancer that overexpresses HER2, the method comprising administering to the patient, a HER2 directed therapy consisting of: an initial dose of 30 mg/m.sup.2 (doxorubicin-HCl equivalent) of doxorubicin in MM302 doxorubicin HER-2 targeted immunoliposomes and 8 mg/kg trastuzumab, followed by the administration to the patient once every three weeks of 30 mg/m.sup.2 (doxorubicin-HCI equivalent) of doxorubicin in the MM302 doxorubicin HER-2 targeted immunoliposomes and 6 mg/kg trastuzumab, to treat the gastric cancer. 2. The method of claim 1, wherein the gastric cancer is a locally advanced/unresectable or metastatic advanced gastric cancer. 3. The method of claim 1, wherein the gastric cancer characterized by overexpression of HER2 receptor is further characterized as being HER2 2+, HER2 3+, or HER2 FISH positive. 4. The method of claim 1, wherein the gastric cancer characterized by overexpression of HER2 receptor is further characterized as expressing an average of at least 200,000 cell surface HER2 receptors per cell. 5. The method of claim 1, wherein the MM302 doxorubicin HER-2 targeted immunoliposomes are administered intravenously over 60 minutes. 6. The method of claim 1, wherein the MM302 doxorubicin HER-2 targeted immunoliposomes are administered before the trastuzumab. 7. The method of claim 1, further comprising one or more of the following: a. the gastric cancer is a locally advanced/unresectable gastric cancer; b. the gastric cancer is a metastatic advanced gastric cancer; c. the gastric cancer characterized by expression of HER2 receptor is further characterized as being HER2 2+ prior to administering the MM302 doxorubicin HER-2 targeted immunoliposomes; d. the gastric cancer characterized by expression of HER2 receptor is further characterized as being HER2 3+ prior to administering the MM302 doxorubicin HER-2 targeted immunoliposomes; e. the gastric cancer characterized by expression of HER2 receptor is further characterized as being HER2 FISH positive prior to administering the MM302 doxorubicin HER-2 targeted immunoliposomes; f. the gastric cancer characterized by overexpression of HER2 receptor is further characterized as expressing an average of at least 200,000 cell surface HER2 receptors per cell; g. the MM302 doxorubicin HER-2 targeted immunoliposomes are administered intravenously over 60 minutes; and h. the MM302 doxorubicin HER-2 targeted immunoliposome are administered before the trastuzumab. 8. A method of treating a patient diagnosed with locally advanced/unresectable gastric cancer or metastatic advanced gastric cancer having a HER2 imunohistochemistry (IHC) score of HER2 2+ or HER2 3+, the method comprising administering to the patient: a. 30 mg/m.sup.2 (doxorubicin-HCl equivalent) of doxorubicin in MM302 doxorubicin HER-2 targeted immunoliposomes in combination with 8 mg/kg trastuzumab, followed by b. administering to the patient once every three weeks 30 mg/m.sup.2 (doxorubicin-HCl equivalent) of doxorubicin in MM302 doxorubicin HER-2 targeted immunoliposomes in combination with 6 mg/kg trastuzumab, to treat the locally advanced/unresectable or metastatic advanced gastric cancer. 9. The method of claim 8, wherein the locally advanced/unresectable gastric cancer or metastatic advanced gastric cancer characterized by overexpression of HER2 receptor is further characterized as being HER2 FISH positive. 10. The method of claim 8, wherein the locally advanced/unresectable gastric cancer or metastatic advanced gastric cancer characterized by overexpression of HER2 receptor is further characterized as expressing an average of at least 200,000 cell surface HER2 receptors per cell. 11. The method of claim 8, wherein the MM302 doxorubicin HER-2 targeted immunoliposomes are administered intravenously over 60 minutes. 12. The method of claim 8, further comprising one or more of the following: a. the gastric cancer is a locally advanced/unresectable gastric cancer; b. the gastric cancer is a metastatic advanced gastric cancer; c. the gastric cancer characterized by expression of HER2 receptor is further characterized as being HER2 2+ prior to administering the MM302 doxorubicin HER-2 targeted immunoliposomes; d. the gastric cancer characterized by expression of HER2 receptor is further characterized as being HER2 3+ prior to administering the MM302 doxorubicin HER-2 targeted immunoliposomes; e. the gastric cancer characterized by expression of HER2 receptor is further characterized as being HER2 FISH positive prior to administering the MM302 doxorubicin HER-2 targeted immunoliposomes; f. the gastric cancer characterized by expression of HER2 receptor further characterized as expressing an average of at least 200,000 cell surface HER2 receptors per cell; g. the MM302 doxorubicin HER-2 targeted immunoliposomes are administered intravenously over 60 minutes; and h. the MM302 doxorubicin HER-2 targeted immunoliposome are administered before the trastuzumab. 13. A method of treating a patient diagnosed with gastric cancer, or locally advanced/unresectable gastric cancer or metastatic advanced gastric cancer, each of which is characterized as being HER2 FISH positive, the method comprising administering to the patient: a. 35 mg/m.sup.2 (doxorubicin-HCl equivalent) of doxorubicin in MM302 doxorubicin HER-2 targeted immunoliposomes in combination with 8 mg/kg trastuzumab, followed by b. administering to the patient once every three weeks 35 mg/m.sup.2 (doxorubicin-HCl equivalent) of doxorubicin in MM302 doxorubicin HER-2 targeted immunoliposomes in combination with 6 mg/kg trastuzumab, to treat the gastric cancer, or locally advanced/unresectable or metastatic advanced gastric cancer. 14. The method of claim 13, wherein the gastric cancer, or locally advanced/unresectable or metastatic advanced gastric cancer characterized as being HER2 FISH positive is further characterized by a HER2 imunohistochemistry (IHC) score of HER2 2+ or HER2 3+ prior to administration of the MM302 doxorubicin HER-2 targeted immunoliposomes. 15. The method of claim 13, wherein the gastric cancer, or locally advanced/unresectable gastric cancer or metastatic advanced gastric cancer characterized as being HER2 FISH positive expresses an average of at least 200,000 cell surface HER2 receptors per cell. 16. The method of claim 13, wherein the MM302 doxorubicin HER-2 targeted immunoliposomes are administered intravenously over 60 minutes. 17. The method of claim 13, wherein the gastric cancer, or locally advanced/unresectable gastric cancer is characterized by a HER2 imunohistochemistry (IHC) score of HER2 2+ or HER2 3+ prior to administration of the MM302 doxorubicin HER-2 targeted immunoliposomes. 18. The method of claim 17, wherein the gastric cancer, or locally advanced/unresectable gastric cancer is characterized by a HER2 imunohistochemistry (IHC) score of HER2 3+ prior to administration of the MM302 doxorubicin HER-2 targeted immunoliposome. 19. The method of claim 13, wherein the metastatic advanced gastric cancer is characterized by a HER2 imunohistochemistry (IHC) score of HER2 2+ or HER2 3+ prior to administration of the MM302 doxorubicin HER-2 targeted immunoliposomes. 20. The method of claim 19, wherein the metastatic advanced gastric cancer is characterized by a HER2 imunohistochemistry (IHC) score of HER2 3+ prior to administration of the MM302 doxorubicin HER-2 targeted immunoliposomes. 21. The method of claim 13, further comprising one or more of the following: a. the gastric cancer is a locally advanced/unresectable gastric cancer; b. the gastric cancer is a metastatic advanced gastric cancer; c. the gastric cancer characterized by expression of HER2 receptor is further characterized as being HER2 2+ prior to administering the MM302 doxorubicin HER-2 targeted immunoliposome; d. the gastric cancer characterized by expression of HER2 receptor is further characterized as being HER2 3+ prior to administering the MM302 doxorubicin HER-2 targeted immunoliposome; e. the gastric cancer characterized by expression of HER2 receptor is further characterized as being HER2 FISH positive prior to administering the MM302 doxorubicin HER-2 targeted immunoliposome; f. the gastric cancer characterized by expression of HER2 receptor further characterized as expressing an average of at least 200,000 cell surface HER2 receptors per cell; g. the MM302 doxorubicin HER-2 targeted immunoliposomes are administered intravenously over 60 minutes; and h. the MM302 doxorubicin HER-2 targeted immunoliposome are administered before the trastuzumab. 22. A method of treating a patient with gastric cancer that overexpresses HER2, the method comprising administering to the patient, a HER2 directed therapy consisting of: an initial dose of 30 mg/m.sup.2 (doxorubicin-HCl equivalent) of doxorubicin in MM302 doxorubicin HER-2 targeted immunoliposomes and 8 mg/kg trastuzumab, followed by the administration to the patient once every three weeks of 30 mg/m.sup.2 (doxorubicin-HCl equivalent) of doxorubicin in the MM302 doxorubicin HER-2 targeted immunoliposomes and 6 mg/kg trastuzumab, to treat the gastric cancer, wherein the doses of MM302 doxorubicin HER-2 targeted immunoliposomes are formulated to contain 10.1 mL of MM-302 doxorubicin HER-2 targeted immunoliposomes at a concentration of 25 mg/mL in 20 mM histidine, 150 mM sodium chloride, and a final solution pH of 6.5.

Details for Patent 9,913,901

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2032-12-03
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2032-12-03
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2032-12-03