# US 9,518,130 B2 · Use of ERBB3 inhibitors in the treatment of triple negative and basal-like breast cancers

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- Number: US 9,518,130 B2
- Document ID: US9518130B2
- Status: Granted
- Kind: B2
- Application number: 14/518,900
- Filed: 2014-10-20
- Published: 2015-05-14
- Granted: 2016-12-13
- Earliest claimed: 2010-03-11
- Assignees: Merrimack Pharmaceuticals, Inc.
- Applicants: Merrimack Pharmaceuticals, Inc.
- Inventors: Victor Moyo; Gabriela Garcia
- Web page: https://patentgrep.com/patent/US9518130B2

## CPC

- C07K 16/32: against translation products of oncogenes
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 35/00: Antineoplastic agents
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07K 16/22: against growth factors {; against growth regulators}
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/3015: {Breast}
- C07K 16/40: against enzymes
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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

## Abstract

Provided are methods of suppressing growth of triple negative breast tumors and basal-like breast tumors by contacting tumor cells with an ErbB3 inhibitor, e.g., an anti-ErbB3 antibody. Also provided are methods for treating triple negative breast cancer or basal-like breast cancer in a patient by administering to the patient an ErbB3 inhibitor, e.g., an anti-ErbB3 antibody. The treatment methods can further comprise selecting a patient having a triple negative breast cancer or basal-like breast cancer and then administering an ErbB3 inhibitor to the patient. The treatment methods also can further comprise administering at least one additional anti-cancer agent to the patient in combination with the ErbB3 inhibitor.

## Claims

### Claim 1

A method of treating a patient having a tumor that expresses ErbB3and is identified as a triple negative breast cancer, the method comprising administering to the patient an effective amount of an anti-ErbB3 antibody, or antigen-binding fragment thereof, comprising a VH CDR1 sequence of SEQ ID NO:3, a VH CDR2 sequence of SEQ ID NO:4 and a VH CDR3 sequence of SEQ ID NO:5, and a VL CDR1 sequence of SEQ ID NO:6, a VL CDR2 sequence of SEQ ID NO:7 and a VL CDR3 sequence of SEQ ID NO:8, that binds to all or a portion of residues 92-104 of SEQ ID NO:41.

### Claim 2 (depends on 1)

The method of claim 1, wherein the anti-ErbB3 antibody binds to the same epitope as an antibody comprising a VH sequence as shown in SEQ ID NO:1 and a VLsequence as shown in SEQ ID NO:2.

### Claim 3 (depends on 1)

The method of claim 1, wherein administration of the effective amount of the anti-ErbB3 antibody suppresses growth of the triple negative breast cancer tumor.

### Claim 4 (depends on 1)

The method of claim 1, wherein the triple negative breast cancer is histopathologically characterized as having a basal-like phenotype.

### Claim 5 (depends on 1)

The method of claim 1, wherein the triple negative breast cancer is histopathologically characterized as having a phenotype other than basal-like.

### Claim 6 (depends on 1)

The method of claim 1, which further comprises administering to the patient an effective amount of at least one additional anti-cancer agent.

### Claim 7 (depends on 6)

The method of claim 6, wherein the at least one additional anti-cancer agent is selected from the group consisting of platinum-based chemotherapy drugs, taxanes, tyrosine kinase inhibitors, anti-EGFR antibodies, anti-ErbB2 antibodies, and combinations thereof.

### Claim 8 (depends on 7)

The method of claim 7, wherein the at least one additional anti cancer agent is a taxane and the taxane is paclitaxel.

### Claim 9 (depends on 6)

The method of claim 6, wherein the at least one additional anti-cancer agent comprises an EGFR inhibitor.

### Claim 10 (depends on 9)

The method of claim 9, wherein the EGFR inhibitor comprises an anti-EGFR antibody.

### Claim 11 (depends on 10)

The method of claim 10, wherein the anti-EGFR antibody is selected from the group consisting of cetuximab, matuzumab, panitumumab, nimotuzumab and mAb 806.

### Claim 12 (depends on 9)

The method of claim 9, wherein the EGFR inhibitor is a small molecule inhibitor of EGFR signaling selected from the group consisting of gefitinib, lapatinib, canertinib, pelitinib, and erlotinib HCL.

### Claim 13 (depends on 6)

The method of claim 6, wherein the at least one additional anti-cancer agent comprises a VEGF inhibitor.

### Claim 14 (depends on 13)

The method of claim 13, wherein the VEGF inhibitor comprises bevacizumab.

### Claim 15 (depends on 1)

The method of claim 1, wherein the triple negative breast cancer tumor is a tumor which scores negative for estrogen receptor (ER) and progesterone receptor and yields a test result of 0, 1+, or 2+ using a semi-quantitative immunohistochemical assay using a polyclonal anti-HER2 primary antibody.

### Claim 16 (depends on 15)

The method of claim 15, wherein the tumor is FISH negative for HER2 gene amplification.

### Claim 17

A method of treating a patient having a tumor that expresses ErbB3and is identified as a triple negative breast cancer which has a basal-like phenotype, the method comprising administering to the patient an effective amount of an anti-ErbB3 antibody, or antigen-binding fragment thereof, comprising a VH CDR1 sequence of SEQ ID NO:3, a VH CDR2 sequence of SEQ ID NO:4 and a VH CDR3 sequence of SEQ ID NO:5, and a VL CDR1 sequence of SEQ ID NO:6, a VL CDR2 sequence of SEQ ID NO:7 and a VL CDR3 sequence of SEQ ID NO:8 that binds to all or a portion of residues 92-104 of SEQ ID NO:41.

### Claim 18 (depends on 17)

The method of claim 17, wherein the anti-ErbB3 antibody binds to the same epitope as an antibody comprising a VH sequence as shown in SEQ ID NO:1 and a VLsequence as shown in SEQ ID NO:2.

### Claim 19 (depends on 17)

The method of claim 17, wherein the administration of the effective amount of the anti-ErbB3 antibody suppresses growth of the breast cancer tumor.

### Claim 20 (depends on 17)

The method of claim 17, which further comprises administering to the patient an effective amount of at least one additional anti-cancer agent.

### Claim 21 (depends on 20)

The method of claim 20, wherein the at least one additional anti-cancer agent is a taxane.

### Claim 22 (depends on 21)

The method of claim 21, wherein the taxane is paclitaxel.