Claims for Patent: 8,623,834

Summary for Patent: 8,623,834

Title:	Compositions including triciribine and trastuzumab and methods of use thereof
Abstract:	This application relates to combination therapies including triciribine and related compounds and trastuzumab or a salt thereof and compositions with reduced toxicity for the treatment and prevention of tumors, cancer, and other disorders associated with abnormal cell proliferation.
Inventor(s):	Cheng; Jin Q. (Tampa, FL), Sebti; Said M. (Tampa, FL)
Assignee:	University of South Florida (Tampa, FL)
Application Number:	13/453,778
Patent Claims:	1. A method for identifying and treating a subject having a tumor or cancer cell with enhanced sensitivity to triciribine (TCN) comprising: (a) determining whether a patient has a tumor or cancer cell with enhanced sensitivity to triciribine or triciribine phosphate comprising: (i) obtaining a biological sample of the tumor or cancer cell from the subject; (ii) measuring the expression level of Akt kinase from the tumor or cancer cell from the subject; and (iii) comparing the expression level of Akt kinase from the tumor or cancer cell to the expression level in a control tissue, wherein a 1.5 fold greater expression of Akt in the tumor or cancer cell compared to a control tissue is indicative of a patient having a tumor or cancer cell with enhanced sensitivity to triciribine or triciribine phosphate; and (b) administering to the patient having a tumor or cancer cell with enhanced sensitivity triciribine or triciribine phosphate: (i) at least one triciribine compound of the formula: ##STR00011## wherein each R.sub.2', R.sub.3', and R.sub.5' are independently hydrogen, optionally substituted phosphate or phosphonate; acyl; alkyl; amide, sulfonate ester; sulfonyl, wherein the phenyl group is optionally substituted with halo, hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, or phosphonate; optionally substituted arylsulfonyl; a lipid; a phospholipid; an amino acid; a carbohydrate; a peptide; or cholesterol; or other pharmaceutically acceptable leaving group that, in vivo, provides a compound wherein R.sub.2', R.sub.3' or R.sub.5' is independently H or mono-, di- or tri-phosphate; wherein R.sup.x and R.sup.y are independently hydrogen, optionally substituted phosphate; acyl; amide, alkyl; aromatic, polyoxyalkylene, optionally substituted arylsulfonyl; a lipid; a phospholipid; an amino acid; a carbohydrate; a peptide; or cholesterol; or other pharmaceutically acceptable leaving group; and R.sub.1 and R.sub.2 each are independently H, optionally substituted straight chained, branched or cyclic alkyl, alkenyl, or alkynyl, CO-alkyl, CO-alkenyl, CO-alkynyl, CO-aryl or heteroaryl, CO-alkoxyalkyl, CO-aryloxyalkyl, CO-substituted aryl, sulfonyl, alkylsulfonyl, arylsulfonyl, or aralkylsulfonyl; (ii) trastuzumab or a salt thereof; and (iii) a pharmaceutically acceptable carrier, wherein said treatment comprises administering 45 mg/m.sup.2 or less of at least one triciribine compound over a one-hour intravenous infusion on days 1, 8, and 15 every 28 days until regression of the tumor or cancer cell is evident. 2. The method of claim 1, wherein the biological sample is taken from breast, pancreas, ovary, colon, or rectum. 3. The method of claim 1, wherein the level of Akt kinase expression is determined by assaying the cancer for the presence of a phosphorylated Akt kinase. 4. The method of claim 1, wherein the level of Akt kinase expression is determined by assaying the cancer for the presence of a phosphorylated Akt kinase with an antibody. 5. The method of claim 1, wherein the administration is repeated at least twice. 6. The method of claim 1, wherein the administration is repeated at least 4 times. 7. The method of claim 1, wherein at least 10 mg/m.sup.2 of the triciribine compound is administered. 8. The method of claim 1, wherein 10 mg/m.sup.2 or less of the triciribine compound is administered. 9. The method of claim 1, wherein the administration is repeated until regression of the cancer is achieved. 10. The method of claim 1, wherein the subject has been diagnosed with a carcinoma, sarcoma, lymphoma, leukemia, or myeloma. 11. The method of claim 1 wherein the subject is mammal. 12. The method of claim 1 wherein the subject is human. 13. The method of claim 1, wherein the triciribine compound is: ##STR00012## 14. The method of claim 1, wherein the triciribine compound is: ##STR00013## 15. The method of claim 1, wherein at least 100 mg of trastuzumab or a salt thereof is administered. 16. The method of claim 1, wherein at least 200 mg of trastuzumab or a salt thereof is administered. 17. The method of claim 1, wherein at least 400 mg of trastuzumab or a salt thereof is administered.

Details for Patent 8,623,834

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	09/25/1998		2024-03-29
Genentech, Inc.	HERCEPTIN	trastuzumab	For Injection	103792	02/10/2017		2024-03-29
Genentech, Inc.	HERCEPTIN HYLECTA	trastuzumab and hyaluronidase-oysk	Injection	761106	02/28/2019		2024-03-29