# US 9,040,500 B2 · Method for treating hematopoietic neoplasms

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- Number: US 9,040,500 B2
- Document ID: US9040500B2
- Status: Granted
- Kind: B2
- Application number: 13/305,612
- Filed: 2011-11-28
- Published: 2012-10-25
- Granted: 2015-05-26
- Earliest claimed: 2007-11-21
- Assignees: OXiGENE, Inc.
- Applicants: David Chaplin; Bronwyn G. Siim
- Inventors: David Chaplin; Bronwyn G. Siim
- Web page: https://patentgrep.com/patent/US9040500B2

## CPC

- A61K 31/6615: Compounds having two or more esterified phosphorus acid groups, e.g. inositol triphosphate, phytic acid
- A61K 31/52: Purines, e.g. adenine
- A61K 31/661: Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion {or mevinphos}
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- 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

This invention relates to methods for treating a hematopoietic neoplasm comprising administering a therapeutically effective amount of a combretastatin compound, or a pharmaceutically acceptable salt thereof, to a subject having a hematological malignancy, wherein the combretastatin compound comprises a catechol or quinone moiety and is capable of forming a reactive oxygen species (ROS) in vivo. The method may further comprise co-administering a second chemotherapeutic agent.

## Claims

### Claim 1

A method of treating a myeloid neoplasm comprising administering a therapeutically effective amount of a combretastatin compound, or a pharmaceutically acceptable salt thereof, to a subject having a hematological malignancy, wherein the combretastatin compound is combretastatin A-1 diphosphate (CA1dP):
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The method of claim 1, wherein the combretastatin compound is a pharmaceutically acceptable salt of combretastatin A-1 diphosphate (CA1dP),-wherein the cation of the salt can be either a divalent cation or two monovalent cations.

### Claim 3 (depends on 2)

The method of claim 2, wherein, the divalent cation is a divalent metal cation.

### Claim 4 (depends on 2)

The method of claim 2, wherein, the monovalent cation is an alkali metal, an aliphatic amine or an ammonium.

### Claim 5 (depends on 2)

The method of claim 2, wherein, the monovalent cation is selected from the group consisting of sodium, TRIS, histidine, ethanolamine, diethanolamine, ethylenediamine, diethylamine, triethanolamine, glucamine, N-methylglucamine, ethylenediamine, 2-(4-imidazolyl)-ethylamine, choline, and hydrabamine.

### Claim 6 (depends on 1)

The method of claim 1, wherein the myeloid neoplasm is an acute myeloid leukemia (AML).

### Claim 7 (depends on 1)

The method of claim 1, wherein the myeloid neoplasm is a refractory organ-infiltrating leukemia.

### Claim 8 (depends on 1)

The method of claim 1, wherein the pharmaceutically acceptable salt is a potassium salt of combretastatin A-1 diphosphate.

### Claim 9 (depends on 1)

The method of claim 1, further comprising co-administering a chemotherapeutic agent to the subject having a myeloid neoplasm.

### Claim 10 (depends on 9)

The method of claim 9, wherein the chemotherapeutic agent is Ara-C, etoposide, thioguanine or cyclophosphamide.

### Claim 11 (depends on 3)

The method of claim 3, wherein the divalent metal cation is magnesium or calcium.