# US 11,026,933 B2 · Compositions and methods for treatment of cancer

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- Number: US 11,026,933 B2
- Document ID: US11026933B2
- Status: Granted
- Kind: B2
- Application number: 16/332,404
- Filed: 2017-09-20
- Published: 2021-01-28
- Granted: 2021-06-08
- Earliest claimed: 2016-09-20
- Assignees: Children's Hospital Medical Center
- Applicants: Children's Hospital Medical Center
- Inventors: Vladimir Kalinichenko; Tatiana Kalin
- Web page: https://patentgrep.com/patent/US11026933B2

## CPC

- A61K 31/4436: containing a heterocyclic ring having sulfur as a ring hetero atom
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 31/475: having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine (vincamine A61K31/4375)
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- 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

Disclosed are methods and compositions for the treatment of a proliferative disorder characterized by increased expression of the FOXM1 gene. Exemplary disorders include adenocarcinoma, melanoma, rhabdomyosarcoma, non-small cell lung cancer (NSCLC), head and neck squamous carcinoma, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma, colon carcinoma, basal cell carcinoma, infiltrating ductal breast carcinoma, anaplastic astrocytoma, glioblastoma, pancreatic carcinoma, gastric cancer, acute myeloid leukemia, lung cancer, liver cancer, breast cancer, prostate cancer, a brain cancer. Kits and articles of manufacture comprising compositions for such treatment are also disclosed.

## Claims

### Claim 1

A method of treating a proliferative disorder due to increased expression of the FOXM1 gene, comprising the step of administering a composition comprising
or a pharmaceutically acceptable salt thereof;
and a pharmaceutically acceptable excipient.

### Claim 2 (depends on 1)

The method of claim 1, wherein said proliferative disorder is selected from a RASopathy, a LAM disease, a fibrotic disorder, a chronic inflammatory disorder, or a cancer.

### Claim 3 (depends on 1)

The method of claim 1, wherein said proliferative disorder is cancer selected from an adenocarcinoma, a melanoma, a rhabdomyosarcoma, a non-small cell lung cancer (NSCLC), a head and neck squamous carcinoma, a hepatocellular carcinoma (HCC), an intrahepatic cholangiocarcinoma, a colon carcinoma, a basal cell carcinoma, an infiltrating ductal breast carcinoma, an anaplastic astrocytoma, a glioblastoma, a pancreatic carcinoma, a gastric cancer, an acute myeloid leukemia, a lung cancer, a liver cancer, a breast cancer, a prostate cancer, and a brain cancer.

### Claim 4 (depends on 1)

The method of claim 1, wherein said proliferative disorder is selected from A549 lung adenocarcinoma and KPC-2 pancreatic carcinoma.

### Claim 5 (depends on 1)

The method of claim 1, wherein said proliferative disorder or said cancer overexpresses FOXM1 and wherein said proliferative disorder or said cancer further contains a RAS mutation.

### Claim 6 (depends on 1)

The method of claim 1, wherein said composition is administered in an amount sufficient to cause one or more of the following: a decrease in tumor growth, a decrease in tumor cell proliferation, increased tumor cell apoptosis, inhibition of metastatic dissemination of cancer, improvement in patient survival, reduced ability of tumor cells to form colonies, and reduced ability of tumor cells to migrate.

### Claim 7 (depends on 1)

The method of claim 1, wherein said composition is administered to said individual in an amount sufficient to inhibit FOXM1 expression in cells overexpressing FOXM1 in said individual following administration of said composition to said individual.

### Claim 8 (depends on 1)

A method of reducing the amount of a chemotherapeutic agent administered to an individual in need thereof, comprising the step of administering a composition of claim 1 to said individual prior to, concurrently with, or following administration of said chemotherapeutic agent.

### Claim 9 (depends on 8)

The method of claim 8, wherein said chemotherapeutic agent is selected from a taxane, a platinum-based agent, an anthracycline, an alkylating agent, a vinca alkaloid, an epothilone, a histone deacetylase inhibitor, a topoisomerase I and II inhibitor, a kinase inhibitor, a nucleotide analog, a peptide antibiotic, and combinations thereof.

### Claim 10

A composition comprising RCM-1, or a pharmaceutically acceptable salt thereof, and one or more chemotherapeutic agents selected from a taxane, a platinum-based agent, an anthracycline, an alkylating agent, a vinca alkaloid, an epothilone, a histone deacetylase inhibitor, a topoisomerase I and II inhibitor, a kinase inhibitor, a nucleotide analog, a peptide antibiotic, and combinations thereof.

### Claim 11 (depends on 10)

The composition of claim 10, further comprising one or more chemotherapeutic agents selected from a taxane, a platinum-based agent, an anthracycline, an alkylating agent, a vinca alkaloid, an epothilone, a histone deacetylase inhibitor, a topoisomerase I and II inhibitor, a kinase inhibitor, a nucleotide analog, a peptide antibiotic, and combinations thereof.