# US 9,040,497 B2 · Treatment and diagnosis of colon cancer

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- Number: US 9,040,497 B2
- Document ID: US9040497B2
- Status: Granted
- Kind: B2
- Application number: 14/480,098
- Filed: 2014-09-08
- Published: 2014-12-25
- Granted: 2015-05-26
- Earliest claimed: 2012-10-31
- Assignees: The Rockefeller University
- Applicants: The Rockefeller University
- Inventors: Sohail F. Tavazoie; Jia M. Loo
- Web page: https://patentgrep.com/patent/US9040497B2

## CPC

- A61K 31/197: the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid (carnitine A61K31/205)
- 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 31/337: having four-membered rings, e.g. taxol
- A61K 31/4168: having a nitrogen attached in position 2, e.g. clonidine
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol
- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 31/7072: having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 1/00: Drugs for disorders of the alimentary tract or the digestive system
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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 present invention discloses novel agents and methods for diagnosis and treatment of colon cancer. Also disclosed are related arrays, kits, and screening methods.

## Claims

### Claim 1

A method for treating a metastatic gastrointestinal cancer in a subject in need thereof, comprising administering to the subject beta-guanidinopropionic acid in an effective amount to suppress metastatic colonization of said gastrointestinal cancer.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cancer is even colorectal cancer or pancreatic cancer.

### Claim 3 (depends on 1)

The method of claim 1, wherein the cancer is gastric cancer.

### Claim 4 (depends on 1)

The method of claim 1, wherein said method comprises the suppression of metastatic colonization of gastrointestinal cancer in the liver in a subject in need thereof.

### Claim 5 (depends on 1)

The method of claim 1, further comprising administering to the subject an additional therapeutic agent.

### Claim 6 (depends on 5)

The method of claim 5, wherein the additional therapeutic agent is selected from the group consisting of cyclocreatine, a RNAi agent, a nucleic acid, a vector, 5-fluorouracil, Oxaliplatin, Irinotecan, Capecitabine, Gemcitabine, Cetuximab, Taxol, Avastin, folinic acid (leucovorin), Regorafenib, Zaltrap, topoisomerase I inhibitors, NKTR-102, Tivantinib, PX-866, Sorafenib, Linifanib, kinase inhibitors, Telatinib, XL281 (BMS-908662), Robatumumab, and IGF1-R inhibitors.

### Claim 7 (depends on 6)

The method of claim 6, wherein the additional therapeutic agent is 5-fluorouracil.

### Claim 8 (depends on 6)

The method of claim 6, wherein the additional therapeutic agent is Capecitabine.

### Claim 9 (depends on 6)

The method of claim 6, wherein the additional therapeutic agent is Gemcitabine.

### Claim 10

A method of treating metastatic cancer in a subject in need thereof comprising:
(a) providing a subject identified to have, or to be at risk of having, metastatic cancer on the basis of the expression level of miR-483-5p and/or miR-551a is below a predetermined reference value or the expression level of CKB and/or SLC6a8 is above a predetermined reference value; and
(b) administering to said subject an effective amount of beta-guanidinopropionic acid.

### Claim 11 (depends on 10)

The method of claim 10, wherein said cancer is selected from the group consisting of colorectal cancer, pancreatic cancer, gastric cancer, esophageal cancer, liver cancer, breast cancer, prostate cancer, lung cancer, and melanoma.

### Claim 12 (depends on 11)

The method of claim 11, wherein said cancer is one of colorectal cancer and gastric cancer.

### Claim 13 (depends on 10)

The method of claim 10, further comprising administering to the subject an additional therapeutic agent.

### Claim 14 (depends on 13)

The method of claim 13, wherein the additional therapeutic agent is selected from the group consisting of cyclocreatine, a RNAi agent, a nucleic acid, a vector, 5-fluorouracil, Oxaliplatin, Irinotecan, Capecitabine, Gemcitabine, Cetuximab, Taxol, Avastin, folinic acid (leucovorin), Regorafenib, Zaltrap, topoisomerase I inhibitors, NKTR-102, Tivantinib, PX-866, Sorafenib, Linifanib, kinase inhibitors, Telatinib, XL281 (BMS-908662), Robatumumab, and IGF1-R inhibitors.

### Claim 15 (depends on 14)

The method of claim 14, wherein the additional therapeutic agent is 5-fluorouracil.

### Claim 16 (depends on 14)

The method of claim 14, wherein the additional therapeutic agent is Capecitabine.

### Claim 17 (depends on 14)

The method of claim 14, wherein the additional therapeutic agent is Gemcitabine.

### Claim 18

A method for treating metastatic cancer in a subject in need thereof, comprising contacting creatine transport channel SLC6a8 with beta-guanidinopropionic acid in an amount effective to suppress metastatic colonization of said cancer.

### Claim 19 (depends on 18)

The method of claim 18, wherein said method comprises the suppression of metastatic colonization of said cancer in the liver.

### Claim 20 (depends on 18)

The method of claim 18, wherein said cancer is selected from the group consisting of colorectal cancer, pancreatic cancer, gastric cancer, esophageal cancer, liver cancer, breast cancer, prostate cancer, lung cancer, and melanoma.

### Claim 21 (depends on 20)

The method of claim 20, wherein said cancer is one of colorectal cancer and gastric cancer.

### Claim 22 (depends on 18)

The method of claim 18, further comprising administering to the subject an additional therapeutic agent.

### Claim 23 (depends on 22)

The method of claim 22, wherein the additional therapeutic agent is selected from the group consisting of cyclocreatine, a RNAi agent, a nucleic acid, a vector, 5-fluorouracil, Oxaliplatin, Irinotecan, Capecitabine, Gemcitabine, Cetuximab, Taxol, Avastin, folinic acid (leucovorin), Regorafenib, Zaltrap, topoisomerase I inhibitors, NKTR-102, Tivantinib, PX-866, Sorafenib, Linifanib, kinase inhibitors, Telatinib, XL281 (BMS-908662), Robatumumab, and IGF1-R inhibitors.

### Claim 24 (depends on 23)

The method of claim 23, wherein the additional therapeutic agent is 5-fluorouracil.

### Claim 25 (depends on 23)

The method of claim 23, wherein the additional therapeutic agent is Capecitabine.

### Claim 26 (depends on 23)

The method of claim 23, wherein the additional therapeutic agent is Gemcitabine.