# US 10,501,537 B2 · Methods for treating cancer

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- Number: US 10,501,537 B2
- Document ID: US10501537B2
- Status: Granted
- Kind: B2
- Application number: 15/325,036
- Filed: 2015-07-07
- Published: 2017-07-13
- Granted: 2019-12-10
- Earliest claimed: 2014-07-07
- Assignees: Dana-Farber Cancer Institute, Inc.
- Applicants: Dana-Farber Cancer Institute, Inc.
- Inventors: Kwok-Kin Wong
- Web page: https://patentgrep.com/patent/US10501537B2

## CPC

- C07K 16/2803: {against the immunoglobulin superfamily}
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 39/39533: {against materials from animals}
- A61P 35/00: Antineoplastic agents
- C07K 16/2818: {against CD28 or CD152}
- G01N 33/575: for cancer
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/31: multispecific
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- G01N 2333/70503: Immunoglobulin superfamily, e.g. VCAMs, PECAM, LFA-3
- 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)
- 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
- 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 present invention provides methods of treating cancer, particularly cancers that had developed resistance to PD-1 and PDL-1 blockade. Also included are methods of identifying therapeutic targets for the treatment of cancer.

## Claims

### Claim 1

A method of treating a subject with a cancer that has acquired resistance to a PD-1 or PDL-1 immunotherapy, comprising administering to said subject an antibody that inhibits the expression or activity of a T cell immunoglobulin and mucin protein 3 (Tim3) and a PD-1 or PDL-1 immunotherapy.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cancer is a KRAS or EGFR mutant cancer.

### Claim 3 (depends on 2)

The method of claim 2, wherein the cancer has a EGFR T790M L858R mutation.

### Claim 4 (depends on 1)

The method of claim 1, wherein said cancer is a lung cancer, melanoma, kidney cancer, a head and neck cancer, bladder cancer or an upper gastrointestinal cancer.

### Claim 5 (depends on 4)

The method of claim 4, wherein the kidney cancer is a renal cell cancer.

### Claim 6 (depends on 4)

The method of claim 4, wherein the lung cancer is a non-small-cell lung cancer.

### Claim 7 (depends on 1)

The method of claim 1, wherein the antibody that inhibits the expression or activity of Tim3 is bi-specific.

### Claim 8 (depends on 1)

The method of claim 1, wherein the PD-1 or PDL-1 immunotherapy is administered concurrently or sequentially with the antibody that inhibits the expression or activity of Tim3.

### Claim 9 (depends on 1)

The method of claim 1, further comprising administering a chemotherapeutic agent or radiation therapy.

### Claim 10 (depends on 9)

The method of claim 9, wherein the chemotherapeutic agent is a targeted therapy.

### Claim 11 (depends on 9)

The method of claim 9, wherein the chemotherapeutic agent is an EGFR tyrosine kinase inhibitor.

### Claim 12 (depends on 11)

The method of claim 11, wherein the EGFR tyrosine kinase inhibitor is WZ4002.

### Claim 13

A method of deriving a clinical benefit from a PD-1 or PDL-1 immunotherapy in a subject with a cancer that has acquired resistance to PD-1 or PDL-1 immunotherapy, comprising administering to said subject an antibody that inhibits the expression or activity of a T cell immunoglobulin and mucin protein 3 (Tim3) and a PD-1 or PDL-1 immunotherapy.