# US 9,517,244 B2 · Therapeutic combinations for use in neoplasia

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- Number: US 9,517,244 B2
- Document ID: US9517244B2
- Status: Granted
- Kind: B2
- Application number: 14/113,365
- Filed: 2012-04-20
- Published: 2014-05-15
- Granted: 2016-12-13
- Earliest claimed: 2011-04-22
- Assignees: University of Florida Research Foundation, Inc.
- Applicants: Satya Narayan; Aruna S. Jaiswal; David A. Ostrov; Sukwon Hong
- Inventors: Satya Narayan; Aruna S. Jaiswal; David A. Ostrov; Sukwon Hong
- Web page: https://patentgrep.com/patent/US9517244B2

## CPC

- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 31/282: Platinum compounds
- A61K 31/495: having six-membered rings with two {or more} nitrogen atoms as the only ring heteroatoms, e.g. piperazine {or tetrazines}(A61K31/48 takes precedence {; with three nitrogen atoms A61K31/53})
- A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495})
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 33/241: Lead; Compounds thereof
- A61K 33/243: Platinum; Compounds thereof
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- 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

## Abstract

The invention features compositions and methods that are useful for the treatment of neoplasia (e.g., pancreatic cancer, colon cancer, brain cancer) by increasing DNA damage, reducing nucleotide synthesis, and reducing base excision repair (BER).

## Claims

### Claim 1

A method for increasing cytotoxicity of a chemotherapeutic agent in a subject, the method comprising administering to the subject NSC-30049 or an analog thereof, an alkylating agent and an agent that binds to ribonucleotide reductase (RR) and reduces nucleotide synthesis relative to a reference;
wherein the analog is of formula:
wherein X is F, Cl, Br, or OH; and
NR3 is

### Claim 2 (depends on 1)

The method of claim 1, wherein NSC-30049 or an analog thereof and the alkylating agent are administered within about 7-14 days or are administered concurrently.

### Claim 3 (depends on 1)

The method of claim 1, wherein NSC-30049 or an analog thereof and the alkylating agent are administered within about 3-5 days or are administered concurrently.

### Claim 4 (depends on 1)

The method of claim 1, wherein the alkylating agent is cisplatin (CDDP).

### Claim 5 (depends on 1)

The method of claim 1, wherein the agent that binds to ribonucleotide reductase (RR) and reduces nucleotide synthesis relative to a reference is gemcitabine (dFdC).

### Claim 6

A method for increasing cytotoxicity of a chemotherapeutic agent in a subject, the method comprising administering to the subject NSC-30049, cisplatin (CDDP), and gemcitabine (dFdC).