# US 7,612,035 B2 · Inhibition of mitogen-activated protein kinase (MAPK) pathway: a selective therapeutic strategy against melanoma

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- Number: US 7,612,035 B2
- Document ID: US7612035B2
- Status: Granted
- Kind: B2
- Application number: 11/155,691
- Filed: 2005-06-20
- Published: 2005-12-01
- Granted: 2009-11-03
- Earliest claimed: 2000-09-01
- Assignees: Van Andel Research Institute
- Applicants: Eunmi (Kay) Koo, legal representative
- Inventors: Han-Mo Koo; George F. Vande Woude; Nicholas S. Duesbery
- Web page: https://patentgrep.com/patent/US7612035B2

## CPC

- A61K 38/4886: {Metalloendopeptidases (3.4.24), e.g. collagenase}
- A61K 31/166: having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
- A61K 31/275: Nitriles; Isonitriles
- A61K 31/352: condensed with carbocyclic rings, e.g. methantheline {(cannabinoids A61K31/658)}
- 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

Inhibitors of the MAPK pathway, including MEK-directed proteases and small molecule inhibitors, are cytotoxic to human melanoma cells in vitro and in vivo via apoptotic mechanisms. These compounds are used to kill melanoma cells and to treat subjects with melanoma, either alone or in combination with other therapeutic modalities.

## Claims

### Claim 1

A method of killing melanoma cells comprising contacting melanoma cells for an effective time with an effective amount of Bacillus anthracis lethal factor (LF), thereby killing the melanoma cells.

### Claim 2 (depends on 1)

The method of claim 1, wherein said contacting is in vivo.

### Claim 3 (depends on 2)

The method of claim 2, wherein said killing results in measurable regression of a melanoma tumor or attenuation of melanoma tumor growth.

### Claim 4

A method of inducing an antitumor response in a mammal having melanoma, comprising administering to a mammal having melanoma an effective amount of Bacillus anthracis lethal factor, wherein administration of the Bacillus anthracis lethal factor results in a cytotoxic effect on melanoma cells, thereby inducing an antitumor response.

### Claim 5 (depends on 4)

The method of claim 4 wherein the antitumor response is:
(a) a partial antitumor response characterized by
(i) at least 50% decrease in the sum of maximal perpendicular diameters of all measurable lesions;
(ii) no evidence of new lesions, and
(iii) no progression of any preexisting lesions, or
(b) a complete antitumor response characterized by the disappearance of all evidence of melanoma disease for at least one month.

### Claim 6 (depends on 5)

The method of claim 5 wherein said antitumor response is a partial antitumor response.

### Claim 7 (depends on 5)

The method of claim 5 wherein said mammal is a human.

### Claim 8

A method of inhibiting the primary growth of melanoma in a mammal which has melanoma, comprising administering to said mammal an effective amount of Bacillus anthracis lethal factor, thereby inhibiting said primary growth of said melanoma.

### Claim 9 (depends on 8)

The method of claim 8 wherein said mammal is a human.