# US 9,433,635 B2 · Effective treatment of ovarian cancer using triciribine and related compounds

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- Number: US 9,433,635 B2
- Document ID: US9433635B2
- Status: Granted
- Kind: B2
- Application number: 14/534,705
- Filed: 2014-11-06
- Published: 2015-07-30
- Granted: 2016-09-06
- Earliest claimed: 2007-09-07
- Assignees: University of South Florida
- Applicants: University of South Florida
- Inventors: Jin Q. Cheng
- Web page: https://patentgrep.com/patent/US9433635B2

## CPC

- A61K 31/7064: containing condensed or non-condensed pyrimidines
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/7056: containing five-membered rings with nitrogen as a ring hetero atom
- A61K 31/706: containing six-membered rings with nitrogen as a ring hetero atom
- A61P 35/00: Antineoplastic agents
- C07H 19/04: Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- G01N 33/57545: of the ovaries
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07H: SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS (derivatives of aldonic or saccharic acids C07C, C07D; aldonic acids, saccharic acids C07C59/105, C07C59/285; cyanohydrins C07C255/16; glycals C07D; compounds of unknown constitution C07G; polysaccharides, derivatives thereof C08B; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification C12N15/00; sugar industry C13)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The inventors have determined, contrary to the prior art and experience, how to successfully use triciribine to treat ovarian cancer by one or a combination of (i) administering triciribine only to patients which according to a diagnostic test described below, exhibit enhanced sensitivity to the drug; (ii) use of a described dosage level that minimizes the toxicity of the drug but yet still exhibits efficacy; or (iii) use of a described dosage regimen that minimizes the toxicity of the drug.

## Claims

### Claim 1

A method for treating ovarian cancer in a mammal comprising:
(i) determining whether the tumor or cancer cell overexpresses an Akt kinase, and
(ii) if the tumor or cancer cell overexpresses Akt kinase, treating the tumor or cancer with an effective amount of 10 mg/m2 or less of a compound of the formula:
wherein each R2′, R3′and R5 ′are independently hydrogen, optionally substituted phosphate or phosphonate; acyl; alkyl; amide, sulfonate ester including alkyl or arylalkyl; sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted with one or more substituents; optionally substituted arylsulfonyl; a lipid, including a phospholipid; an amino acid; a carbohydrate; a peptide; or cholesterol; or other pharmaceutically acceptable leaving group that, in vivo, provides a compound wherein R2′, R3′or R5 is independently H or mono-, di- or tri-phosphate;
wherein Rx and Ry are independently hydrogen, optionally substituted phosphate; acyl; amide, alkyl; aromatic, polyoxyalkylene such as polyethyleneglycol, optionally substituted arylsulfonyl; a lipid, including a phospholipid; an amino acid; a carbohydrate; a peptide; or cholesterol; or other pharmaceutically acceptable leaving group;
wherein R1 and R2 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, aralkylsulfonyl.

### Claim 2 (depends on 1)

The method of claim 1, wherein the subject has been diagnosed with ovarian cancer.

### Claim 3 (depends on 1)

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.

### Claim 4 (depends on 1)

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.

### Claim 5

A method of treating ovarian cancer in a mammal wherein the ovarian cancer overexpresses Akt kinase comprising administering to the mammal an effective amount of 10 mg/m2 or less of at least one compound selected from the group consisting of:
wherein each R2′, R3′and R5′ are independently hydrogen, optionally substituted phosphate or phosphonate; acyl; alkyl; amide, sulfonate ester including alkyl or arylalkyl; sulfonyl, including methanesulfonyl and benzyl, wherein the phenyl group is optionally substituted with one or more substituents; optionally substituted arylsulfonyl; a lipid, including a phospholipid; an amino acid; a carbohydrate; a peptide; or cholesterol; or other pharmaceutically acceptable leaving group that, in vivo, provides a compound wherein R2′, R3′or R5′ is independently H or mono-, di- or tri-phosphate;
wherein Rx and Ry are independently hydrogen, optionally substituted phosphate; acyl; amide, alkyl; aromatic, polyoxyalkylene such as polyethyleneglycol, optionally substituted arylsulfonyl; a lipid, including a phospholipid; an amino acid; a carbohydrate; a peptide; or cholesterol; or other pharmaceutically acceptable leaving group;
wherein R1 and R2 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, alkyl sulfonyl, aryl sulfonyl, aralkyl sulfonyl;
wherein the compound is administered one time per week for three weeks followed by a one week period wherein the compound is not administered.

### Claim 6 (depends on 5)

The method of claim 5, wherein the dosing schedule is repeated at least twice.

### Claim 7 (depends on 5)

The method of claim 5, wherein the dosing schedule is repeated at least 4 times.