# US 2010/0166744 A1 · Use of anti-egfr antibodies in treatment of egfr mutant mediated disease

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

- Number: US 2010/0166744 A1
- Document ID: US20100166744A1
- Status: Published application
- Kind: A1
- Application number: 12/449,129
- Filed: 2008-01-24
- Published: 2010-07-01
- Earliest claimed: 2007-01-25
- Assignees: Dana-Farber Cancer Institute, Inc.
- Inventors: Kwok-Kin Wong
- Web page: https://patentgrep.com/patent/US20100166744A1

## CPC

- C07K 16/2863: {against receptors for growth factors, growth regulators}
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A61K 2039/505: {comprising antibodies}
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

The present invention relates to the treatment of EGFR-mediated disease, particularly cancer, which is resistant to tyrosine kinase inhibitor therapies. Methods for treatment of cancer and reduction of tumor growth in individuals with secondary EGFR mutations, particularly tyrosine kinase domain mutations, resistant to standard therapy are provided. The invention provides methods for the treatment of tyrosine kinase inhibitor resistant cancers with anti-EGFR antibodies. Methods for treatment of recurrent lung cancer, including non-small cell lung carcinoma which is resistant to tyrosine kinase inhibitors, with the antibody anti-EGFR mAb806 are described.

## Claims

### Claim 1

A method of treating tyrosine kinase inhibitor resistant EGFR-mediated disease in a mammal, wherein said resistant EGFR-mediated disease is a result of a secondary mutation in EGFR to generate a mutant EGFR and wherein said mutation is distinct from the EGFR vIII mutation, comprising administering to said mammal an effective amount of an anti-EGFR antibody capable of binding to and inhibiting the mutant EGFR.

### Claim 2 (depends on 1)

The method of claim 1 wherein the secondary EGFR mutation is an EGFR tyrosine kinase domain mutation.

### Claim 3 (depends on 2)

The method of claim 2 wherein the tyrosine kinase domain mutation is T790M.

### Claim 4 (depends on 1)

The method of claim 1 wherein the anti-EGFR antibody is mAb806 antibody or an active fragment thereof.

### Claim 5 (depends on 4)

The method of claim 4 wherein mAb806 is a recombinant antibody or a humanized antibody.

### Claim 6 (depends on 1)

The method of claim 1 wherein the anti-EGFR antibody is selected from ABX-EGF (panitumumab), DH8.3, L8A4, and or active fragments thereof.

### Claim 7 (depends on 1)

The method of claim 1 wherein the EGFR-mediated disease is cancer and is selected from glioblastoma, head and neck cancer, pancreatic cancer, lung cancer, cancer of the nervous system, gastrointestinal cancer, prostate cancer, ovarian cancer, breast cancer, kidney cancer, retina cancer, skin cancer, liver cancer, genital-urinary cancer, and bladder cancer.

### Claim 8 (depends on 7)

The method of claim 7 wherein the cancer is lung adenocarcinoma, lung squamous cell carcinoma or non-small cell lung cancer.

### Claim 9

A method for reducing EGFR-mediated tumor growth in a cancer patient, wherein said cancer patient has been previously treated with one or more tyrosine kinase inhibitor and has developed recurrent disease and tumor growth, comprising administering to said patient an effective amount of an anti-EGFR antibody such that the recurrent disease and tumor growth is inhibited and reduced.

### Claim 10 (depends on 9)

The method of claim 9 wherein the anti-EGFR antibody is mAb806 antibody or an active fragment thereof.

### Claim 11 (depends on 10)

The method of claim 10 wherein mAb806 is a recombinant antibody or a humanized antibody.

### Claim 12 (depends on 9)

The method of claim 9 wherein the anti-EGFR antibody is selected from ABX-EGF (panitumumab), DH8.3, L8A4, and or active fragments thereof.

### Claim 13 (depends on 9)

The method of claim 9 wherein the cancer patient has developed a secondary EGFR mutation which is an EGFR tyrosine kinase domain mutation.

### Claim 14 (depends on 13)

The method of claim 13 wherein the tyrosine kinase domain mutation is T790M.

### Claim 15

A method of treating EGFR-mediated cancer in a mammal comprising administering to said mammal a tyrosine kinase inhibitor and anti-EGFR antibody, wherein said anti-EGFR antibody is administered after treatment with the tyrosine kinase inhibitor as a second line of therapy to inhibit potential secondary mutant EGFRs resistant to tyrosine kinase inhibitors.

### Claim 16 (depends on 15)

The method of claim 15 wherein the EGFR-mediated cancer is selected from glioblastoma, head and neck cancer, pancreatic cancer, lung cancer, cancer of the nervous system, gastrointestinal cancer, prostate cancer, ovarian cancer, breast cancer, kidney cancer, retina cancer, skin cancer, liver cancer, genital-urinary cancer, and bladder cancer.

### Claim 17 (depends on 16)

The method of claim 16 wherein the cancer is lung adenocarcinoma, lung squamous cell carcinoma or non-small cell lung cancer.

### Claim 18 (depends on 15)

The method of claim 15 wherein the tyrosine kinase inhibitor is a reversible tyrosine kinase inhibitor.

### Claim 19 (depends on 18)

The method of claim 18 wherein the reversible tyrosine kinase inhibitor is an aniliniquinazoline and is selected from gefitinib, erlotinib, AG1478, ST1571 and SU-6668.

### Claim 20 (depends on 15)

The method of claim 15 wherein the tyrosine kinase inhibitor is an irreversible tyrosine kinase inhibitor.

### Claim 21 (depends on 20)

The method of claim 20 wherein the irreversible tyrosine kinase inhibitor is selected from EKB-569, EK1-569, HKI-272, HK1-357 and BIBW 2992.