# US 2013/0156764 A1 · Neutralization of flt3 ligand as a leukemia therapy

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2013/0156764 A1
- Document ID: US20130156764A1
- Status: Published application
- Kind: A1
- Application number: 13/634,439
- Filed: 2011-03-14
- Published: 2013-06-20
- Earliest claimed: 2010-03-12
- Assignees: The Johns Hopkins University
- Inventors: Mark J. Levis; Donald Small
- Web page: https://patentgrep.com/patent/US20130156764A1

## CPC

- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 31/136: having the amino group directly attached to the aromatic ring, e.g. benzeneamine
- A61K 31/403: condensed with carbocyclic rings, e.g. carbazole
- A61K 31/404: Indoles, e.g. pindolol
- A61K 31/416: condensed with carbocyclic ring systems, e.g. indazole
- A61K 31/44: Non condensed pyridines; Hydrogenated derivatives thereof
- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/553: having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- 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 38/1793: {for cytokines; for lymphokines; for interferons}
- A61K 38/45: Transferases (2)
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- 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
- 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 herein are methods and compositions for treating leukemia and preventing leukemia relapse related to the administration of agents that inhibit the binding of FLT3 ligand to FLT3.

## Claims

### Claim 1

A method of treating leukemia in a subject comprising administering to the subject a therapeutically effective amount of a first agent that inhibits the tyrosine kinase activity of FLT3 and administering to the subject a therapeutically effective amount of a second agent that inhibits the binding of FLT3L to FLT3.

### Claim 2 (depends on 1)

The method of claim 1, wherein the first agent is a small molecule.

### Claim 3 (depends on 2)

The method of claim 2, wherein the first agent is lestaurtinib, midostaurin, sorafenib, KW-2449, or AC220.

### Claim 4 (depends on 1)

The method of claim 1, wherein the second agent is an antibody or antibody fragment that specifically binds to FLT3L.

### Claim at position 5

5-7. (canceled)

### Claim 8 (depends on 1)

The method of claim 1, wherein the second agent is a polypeptide comprising a portion of the FLT3 extracellular domain.

### Claim 9 (depends on 8)

The method of claim 8, wherein the polypeptide further comprises an immunoglobulin constant domain or portion thereof.

### Claim 10 (depends on 1)

The method of claim 1, further comprising administering a chemotherapy to the subject.

### Claim 11 (depends on 10)

The method of claim 10, wherein the chemotherapy comprises:
administering mitoxatrone, etoposide and cytarabine to the subject;
administering high dose cytarabine to the subject; or
administering cytarabine, daunorubicin and etoposide to the subject.

### Claim 12 (depends on 1)

The method of claim 1, wherein leukemia cells in the subject comprise a FLT3 activating mutation.

### Claim 13 (depends on 12)

The method of claim 12, wherein the FLT3 activating mutation is an internal tandem duplication in the FLT3 juxtamembrane region or a point mutation in the FLT3 tyrosine kinase domain.

### Claim 14 (depends on 1)

The method of claim 1, wherein the leukemia is AML, ALL or CML.

### Claim 15 (depends on 1)

The method of claim 1, wherein the administration of the second agent occurs after the administration of the first agent.

### Claim 16

A method of preventing a leukemia relapse in a subject who had previously been treated for leukemia with a first agent that inhibits the tyrosine kinase activity of FLT3, the method comprising administering to the subject a therapeutically effective amount of a second agent that inhibits the binding of FLT3L to FLT3.

### Claim 17 (depends on 16)

The method of claim 16, wherein the first agent is a small molecule.

### Claim 18 (depends on 17)

The method of claim 17, wherein the first agent is lestaurtinib, midostaurin, sorafenib, KW-2449, or AC220.

### Claim 19 (depends on 16)

The method of claim 16, wherein the second agent is an antibody or antibody fragment that specifically binds to FLT3L.

### Claim 20

(canceled)

### Claim 21 (depends on 16)

The method of claim 16, wherein the second agent is an antibody or antibody fragment that specifically binds to FLT3.

### Claim at position 20

22-24. (canceled)

### Claim 25 (depends on 16)

The method of claim 16, wherein the previous leukemia treatment further comprised administration of a chemotherapy to the subject.

### Claim 26

(canceled)

### Claim 27 (depends on 16)

The method of claim 16, wherein the leukemia cells of the subject comprise a FLT3 activating mutation.

### Claim at position 24

28-29. (canceled)

### Claim 30

A kit for treating leukemia in a subject comprising a therapeutically effective amount of a first agent that inhibits the tyrosine kinase activity of FLT3 and a therapeutically effective amount of a second agent that inhibits the binding of FLT3L to FLT3.

### Claim at position 26

31-40. (canceled)
