# US 12,213,977 B2 · Methods and compositions for treating melanoma

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- Number: US 12,213,977 B2
- Document ID: US12213977B2
- Status: Granted
- Kind: B2
- Application number: 16/625,075
- Filed: 2018-06-27
- Published: 2020-05-28
- Granted: 2025-02-04
- Earliest claimed: 2017-06-28
- Assignees: The Regents of the University of California
- Applicants: The Regents of the University of California
- Inventors: Thomas G. Graeber; Jennifer Tsoi; Antoni Ribas; Lidia Robert; Nicolaos Palaskas
- Web page: https://patentgrep.com/patent/US12213977B2

## CPC

- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/437: the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
- A61K 35/17: Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes (when activated by a specific antigen A61K39/00)
- C07K 16/2818: {against CD28 or CD152}
- G01N 33/5751: of the skin, e.g. melanoma
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The current methods and compositions provide for a novel therapeutic method for treating patients diagnosed with melanoma, especially those that have become resistant to certain other therapies. Accordingly, certain aspects of the disclosure relate to a method for treating melanoma in a subject, the method comprising administering a composition comprising a ferroptosis-inducing agent or other dedifferentiated melanoma-targeting agent to the subject.

## Claims

### Claim 1

A method for treating or preventing BRAF inhibitor resistance in a subject having dedifferentiated melanoma, the method comprising administering a GPX4 inhibitor and a BRAF inhibitor in parallel.

### Claim 2 (depends on 1)

The method of claim 1, wherein the BRAF inhibitor comprises encorafenib, binimetinib, vemurafenib, or combinations thereof.

### Claim 3 (depends on 1)

The method of claim 1, wherein the GPX4 inhibitor comprises a direct GPX4 inhibitor.

### Claim 4 (depends on 1)

The method of claim 1, wherein the GPX4 inhibitor comprises one or more of RSL3, RSL5, ML162, ML210, DPI7, DPI10, DPI12, DPI13, DPI17, DPI18, DPI19, CIL56, FIN56, salts or derivatives thereof.

### Claim 5 (depends on 2)

The method of claim 2, wherein the BRAF inhibitor comprises vemurafenib.

### Claim 6

A method for treating a subject having dedifferentiated melanoma, the method comprising administering a GPX4 inhibitor to the subject, wherein the subject is being treated in parallel with a BRAF inhibitor.

### Claim 7 (depends on 6)

The method of claim 6, wherein the BRAF inhibitor comprises encorafenib, binimetinib, vemurafenib, or combinations thereof.

### Claim 8 (depends on 7)

The method of claim 7, wherein the BRAF inhibitor comprises vemurafenib.

### Claim 9 (depends on 6)

The method of claim 6, wherein the GPX4 inhibitor comprises a direct GPX4 inhibitor.

### Claim 10 (depends on 6)

The method of claim 6, wherein the GPX4 inhibitor comprises one or more of RSL3, RSL5, ML162, ML210, DPI7, DPI10, DPI12, DPI13, DPI17, DPI18, DPI19, CIL56, FIN56, salts or derivatives thereof.

### Claim 11 (depends on 6)

The method of claim 6, wherein the subject has been determined to have melanoma cells with reduced expression of MITF; wherein the reduced expression of MITF is reduced compared to the level of expression of MITF in a cancerous sample with a melanocytic phenotype.

### Claim 12 (depends on 6)

The method of claim 6, wherein the subject has been determined to have melanoma cells with reduced expression of MITF; wherein the reduced expression of MITF is reduced compared to the level of expression of MITF in a cancerous sample with a melanocytic phenotype.