# US 9,040,047 B2 · Combinations of anti ErbB antibodies for the treatment of cancer

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

- Number: US 9,040,047 B2
- Document ID: US9040047B2
- Status: Granted
- Kind: B2
- Application number: 14/118,243
- Filed: 2012-05-16
- Published: 2014-03-27
- Granted: 2015-05-26
- Earliest claimed: 2011-05-16
- Assignees: Yeda Research and Development Co. Ltd.
- Applicants: Michael Sela; Yosef Yarden; Bilha Schechter; Ruth Maron
- Inventors: Michael Sela; Yosef Yarden; Bilha Schechter; Ruth Maron
- Web page: https://patentgrep.com/patent/US9040047B2

## CPC

- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61N 5/10: X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence)
- A61P 35/00: Antineoplastic agents
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/32: against translation products of oncogenes
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- 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)
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

An article-of-manufacture is provided. The article-of-manufacture comprises a packaging material identified for treating cancer, packaging: (i) an anti-EGFR antibody comprising the CDR sequences of anti EGFR 565 (CNCM Deposit Number I-4262); and (ii) an anti-ErbB-2 antibody comprising the CDR sequences of anti ErbB-2 L431 (CNCM Deposit Number I-4115), anti ErbB-2 L26 (CNCM Deposit Number I-4113) or anti ErbB-2 N12 (CNCM Deposit Number I-4112), or (iii) an anti-EGFR antibody comprising the CDR sequences of anti EGFR 111 (CNCM Deposit Number I-4261); and (iv) an anti-ErbB-2 antibody comprising the CDR sequences of anti ErbB-2 L431 (CNCM Deposit Number I-4115). Also provided are pharmaceutical compositions and methods of using the above antibodies as well as other antibody combinations for the treatment of cancer.

## Claims

### Claim 1

An article-of-manufacture comprising a packaging material identified for treating cancer expressing EGFR and ErbB-2, packaging:
(i) an anti-EGFR antibody comprising the CDR sequences of anti EGFR 565 (CNCM Deposit Number I-4262); and
(ii) an anti-ErbB-2 antibody comprising the CDR sequences of anti ErbB-2 L431 (CNCM Deposit Number I-4115), anti ErbB-2 L26 (CNCM Deposit Number I-4113) or anti ErbB-2 N12 (CNCM Deposit Number I-4112);
or
(iii) an anti-EGFR antibody comprising the CDR sequences of anti EGFR 111 (CNCM Deposit Number I-4261); and
(iv) an anti-ErbB-2 antibody comprising the CDR sequences of anti ErbB-2 L431 (CNCM Deposit Number I-4115).

### Claim 2

A pharmaceutical composition comprising as active ingredients:
(i) an anti-EGFR antibody comprising the CDR sequences of anti EGFR 565 (CNCM Deposit Number I-4262); and
(ii) an anti-ErbB-2 antibody comprising the CDR sequences of anti ErbB-2 L431 (CNCM Deposit Number I-4115), anti ErbB-2 L26 (CNCM Deposit Number I-4113) or anti ErbB-2 N12 (CNCM Deposit Number I-4112);
or
(iii) an anti-EGFR antibody comprising the CDR sequences of anti EGFR 111 (CNCM Deposit Number I-4261); and
(iv) an anti-ErbB-2 antibody comprising the CDR sequences of anti ErbB-2 L431 (CNCM Deposit Number I-4115)
and a pharmaceutically acceptable carrier or diluent.

### Claim 3 (depends on 2)

The pharmaceutical composition of claim 2, wherein said active ingredients are in a co-formulation.

### Claim 4 (depends on 2)

The pharmaceutical composition of claim 2, wherein said active ingredients are in separate formulations.

### Claim 5

A method of treating cancer expressing EGFR and ErbB-2 in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of:
(i) an anti-EGFR antibody comprising the CDR sequences of anti EGFR 565 (CNCM Deposit Number I-4262); and
(ii) an anti-ErbB-2 antibody comprising the CDR sequences of anti ErbB-2 L431 (CNCM Deposit Number I-4115), anti ErbB-2 L26 (CNCM Deposit Number I-4113) or anti ErbB-2 N12 (CNCM Deposit Number I-4112), thereby treating cancer expressing EGFR and ErhB-2 in the subject.

### Claim 6

A method of treating pancreatic cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of:
(i) an anti-EGFR antibody comprising the CDR sequences of anti EGFR 565 (CNCM Deposit Number I-4262); and
(i) an anti-EGFR antibody comprising the CDR sequences of anti EGFR 111 (CNCM Deposit Number I-4261),
thereby treating cancer in the subject.

### Claim 7

A method of treating pancreatic cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a single anti ErbB-2 antibody comprising the CDR sequences of anti ErbB-2 N12 (CNCM Deposit Number I-4112), thereby treating cancer in the subject.

### Claim 8 (depends on 1)

The article-of-manufacture of claim 1, wherein at least one of said antibodies is a humanized or partially humanized antibody.

### Claim 9 (depends on 1)

The article-of-manufacture of claim 1, wherein said cancer is pancreatic cancer.

### Claim 10 (depends on 1)

The article-of-manufacture of claim 1, wherein said cancer expresses moderate to high levels of EGFR (above 2×105 molecules/cell) and low levels of ErbB-2 (below 1×105 molecules/cell).

### Claim 11 (depends on 10)

The article-of-manufacture of claim 10, wherein said cancer is selected from the group consisting of pancreatic cancer, prostate cancer, lung cancer and head and neck cancer.

### Claim 12 (depends on 5)

The method of claim 5, further comprising subjecting the subject to a therapy selected from the group consisting of a radiotherapy and a chemotherapy.

### Claim 13 (depends on 5)

The method of claim 5, wherein said administering comprises multiple administrations.

### Claim 14 (depends on 13)

The method of claim 13, wherein said multiple administrations comprise weekly administrations.

### Claim 15 (depends on 5)

The method of claim 5, wherein at least one of said antibodies is a humanized or partially humanized antibody.

### Claim 16 (depends on 6)

The method of claim 6, wherein at least one of said antibodies is a humanized or partially humanized antibody.

### Claim 17 (depends on 5)

The method of claim 5, wherein said cancer is pancreatic cancer.

### Claim 18 (depends on 5)

The method of claim 5, wherein said cancer expresses moderate to high levels of EGFR (above 2×105 molecules/cell) and low levels of ErbB-2 (below 1×105 molecules/cell).

### Claim 19 (depends on 18)

The method of claim 18, wherein said cancer is selected from the group consisting of pancreatic cancer, prostate cancer, lung cancer and head and neck cancer.