Claims for Patent: 7,541,342

Summary for Patent: 7,541,342

Title:	Use of PKC-activating compounds as cardioprotectants and as apoptosis-inducing anti-tumor agents
Abstract:	Compounds for the inducing apoptosis in cancer cells are described. The described compounds induce the translocation of protein kinase C-.delta. to the mitochondria and the phosphorylation of mitochondrial phospholipid scramblase 3. The compounds also provide cardioprotection through the translocation and activation of protein kinase C-.epsilon. in cardiomyocytes, thereby inhibiting apoptosis in carciomyocytes.
Inventor(s):	Lothstein; Leonard (Eads, TN), Israel; Mervyn (Germantown, TN), Sweatman; Trevor (Memphis, TN), Hofmann; Polly A. (Memphis, TN)
Assignee:	University of Tennessee Research Foundation (Knoxville, TN)
Application Number:	11/369,225
Patent Claims:	1. A method for providing cardioprotection in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of Formula (I): ##STR00010## wherein: A comprises a C.sub.4-C.sub.8 alkanoate moiety; R.sub.1 is H; R.sub.2 is benzyl; and R.sub.3 is H or methoxy; or a pharmaceutically acceptable salt thereof. 2. The method of claim 1, wherein A is selected from the group consisting of: ##STR00011## 3. The method of claim 2, wherein the compound of Formula I is selected from the group consisting of: ##STR00012## 4. The method of claim 1, wherein the administering to the subject an effective amount of a compound of Formula (I) induces the activation of protein kinase C-epsilon (PKC-.epsilon.) in a cardiomyocyte, thereby inducing a cardioprotective effect. 5. A method of treating a cancer, the method comprising administering to a subject in need of treatment thereof an effective amount of a compound of Formula (I): ##STR00013## wherein: A comprises a C4-C8 alkanoate moiety; R1 is H; R2 is benzyl; and R3 is H or methoxy; or a pharmaceutically acceptable salt thereof; and administering to the subject in need of treatment thereof an additional therapeutic agent comprising one or more anti-cancer agents; wherein the administering of the compound of Formula (I) and the additional therapeutic agent provides a synergistic effect. 6. The method of claim 5, wherein the additional therapeutic agent comprises imatinib mesylate. 7. The method of claim 5, wherein the cancer is chronic myeloid leukemia (CML). 8. The method of claim 1, wherein the subject is undergoing treatment for a cancer. 9. The method of claim 1, wherein the compound of Formula (I) is administered in a dose that would be cardiotoxic for an anthracycline compound having a structure other than that of Formula (I). 10. The method of claim 1, further comprising administering the compound of Formula (I) in combination with at least one or more additional therapeutic agents. 11. The method of claim 10, wherein the one or more additional therapeutic agents comprise at least one or more anti-cancer agents. 12. The method of claim 11, wherein the at least one or more anti-cancer agents is selected from the group consisting of antimetabolites, antimicrotubules, alkylating agents, and antibodies. 13. The method of claim 12, wherein the at least one or more additional therapeutic agents comprises a monoclonal antibody. 14. The method of claim 13, wherein the monoclonal antibody comprises trastuzumab. 15. The method of claim 8, wherein the cancer comprises a human epidermal growth factor receptor 2 (HER2) positive breast cancer. 16. A method for treating a drug resistant cancer, wherein the drug resistant cancer is adult chronic myeloid leukemia (CML), the method comprising administering to a subject in need of treatment thereof an effective amount of a compound of Formula (I): ##STR00014## wherein: A comprises a C.sub.4-C.sub.8 alkanoate moiety; R.sub.1 is H; R.sub.2 is benzyl; and R.sub.3 is H or methoxy; or a pharmaceutically acceptable salt thereof. 17. The method of claim 16, wherein A is selected from the group consisting of: ##STR00015## 18. The method of claim 17, wherein the compound of Formula (I) is selected from the group consisting of: ##STR00016## 19. The method of claim 16, wherein the administering an effective amount of a compound of Formula (I) provides cardioprotection to the subject in need of treatment thereof. 20. The method of claim 16, wherein the drug-resistant cancer is resistant to imatinib mesylate.

Details for Patent 7,541,342

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2025-03-04
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2025-03-04
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2025-03-04