# US 2014/0154340 A1 · Methods to treat cancer using cyclosporine and cyclosporine derivatives

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- Number: US 2014/0154340 A1
- Document ID: US20140154340A1
- Status: Published application
- Kind: A1
- Application number: 14/057,780
- Filed: 2013-10-18
- Published: 2014-06-05
- Earliest claimed: 2011-04-18
- Assignees: The Trustees of Columbia University in the City of New York
- Applicants: The Trustees of Columbia University In the City of New York
- Inventors: John DITTMAR; Rodney J. ROTHSTEIN; Robert J.D. REID; Ramon PARSONS; Matthew MAURER; Jacquelyn SHAW
- Web page: https://patentgrep.com/patent/US20140154340A1

## CPC

- A61K 38/13: Cyclosporins
- A61K 31/501: not condensed and containing further heterocyclic rings
- A61K 38/12: Cyclic peptides {, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C (A61K38/043 - A61K38/046 take precedence)}
- 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

Methods to treat certain types of cancer with cyclophilin inhibitors.

## Claims

### Claim 1

A method to treat cancer in a subject in need of treatment therefor, the method comprising contacting a PTEN negative cancer in the subject with an agent which inhibits cyclophilin activity.

### Claim 2

A method to reduce growth of a cancer cell in a subject in need of treatment therefor, the method comprising: contacting a PTEN negative cancer cell in the subject with a therapeutic amount of an agent which inhibits cyclophilin activity, whereby the growth of the cancer is reduced compared to PTEN positive cancer cells.

### Claim 3

A method to induce apoptosis of a cancer cell in a subject in need of treatment therefor, the method comprising: contacting a PTEN negative cancer cell in the subject with a therapeutic amount of an agent which inhibits cyclophilin activity, whereby apoptosis of the cancer cell is induced and the subject is treated.

### Claim 4

A method to treat cancer in a subject in need of treatment therefor, the method comprising: administering to a subject diagnosed with a PTEN negative cancer a therapeutic amount of an agent which inhibits cyclophilin activity, whereby the cancer is treated.

### Claim 5 (depends on 4)

The method of claim 4, wherein the agent which inhibits cyclophilin activity is a cyclosporine.

### Claim 6 (depends on 5)

The method of claim 5, wherein the cyclosporine is a naturally occurring cyclosporine.

### Claim 7 (depends on 6)

The method of claim 6, wherein the cyclosporine is cyclosporine A.

### Claim 8 (depends on 5)

The method of claim 5, wherein the cyclosporine is a cyclosporine derivative.

### Claim 9 (depends on 8)

The method of claim 8, wherein the cyclosporine derivative is a non-immunosuppressive derivative.

### Claim 10 (depends on 5)

The method of claim 5 wherein the cyclosporine derivative is the agent of Formula I, the agent of Formula II, NIM-811, SCY-635, DEBIO-025, Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula VIII, or any combination thereof.

### Claim 11

The method of claim -4, wherein the agent which inhibits cyclophilin activity is sanglifehrin.

### Claim 12 (depends on 11)

The method of claim 11, wherein the sanglifehrin is sanglifehrinA, sanglifehrinB, sanglifehrinC, sanglifehrinD, or any combination thereof.

### Claim 13 (depends on 4)

The method of claim 4, wherein the cancer is breast cancer, prostate cancer, colon cancer, glioblastoma, endometrial cancer, lung cancer, thyroid cancer, lymphomas, ovarian cancer, or a combination thereof.

### Claim 14 (depends on 13)

The method of claim 13, wherein the cancer is a triple negative breast cancer.

### Claim 15 (depends on 13)

The method of claim 13, wherein the cancer is a hormone negative prostate cancer.

### Claim 16 (depends on 4)

The method of claim 4, wherein the therapeutic amount of the agent which inhibits cyclophilin activity is administered in a combination with a therapeutic amount of a PARP inhibitor or a DNA cross-linking agent, or a combination thereof.

### Claim 17 (depends on 16)

The method of claim 16, wherein the DNA cross-linking agent is cisplatin, mitomycin C, cyclophosphamide, chlorambucil, uramustine, ifosfamide, melphalan, bendamustine, carmustine, or any combination thereof.

### Claim 18 (depends on 17)

The method of claim 17, wherein the PARP inhibitor is olaparib.