# US 9,518,988 B2 · Antibodies and methods of using same for treating ErbB/ErbB ligands associated diseases

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- Number: US 9,518,988 B2
- Document ID: US9518988B2
- Status: Granted
- Kind: B2
- Application number: 13/641,174
- Filed: 2011-03-22
- Published: 2013-02-07
- Granted: 2016-12-13
- Earliest claimed: 2010-04-18
- Assignees: Yeda Research and Development Co. Ltd.
- Applicants: Moshit Lindzen; Yosef Yarden
- Inventors: Moshit Lindzen; Yosef Yarden
- Web page: https://patentgrep.com/patent/US9518988B2

## CPC

- G01N 33/5758: {involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites}
- A61K 31/7068: having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- 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}
- G01N 33/5011: {for testing antineoplastic activity}
- G01N 33/5752: of the lungs
- G01N 33/57525: of the liver or pancreas
- G01N 33/5759: {involving compounds localised on the membrane of tumour or cancer cells}
- G01N 33/577: involving monoclonal antibodies {binding reaction mechanisms characterised by the use of monoclonal antibodies (G01N33/5302 - G01N33/576 take precedence)}
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- 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
- G01N 2333/485: Epidermal growth factor [EGF] (urogastrone)
- G01N 2333/495: Transforming growth factor [TGF]
- G01N 2500/00: Screening for compounds of potential therapeutic value
- 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)
- 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
- 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

A method of selecting a target for treatment of a hyperproliferative disease in a subject in need thereof is disclosed. The method comprising analyzing an amount and/or activity of at least one ErbB ligand in a biological sample from the subject, wherein an ErbB ligand which shows an up-regulated amount and/or activity compared to a non-hyperproliferative cell or tissue above a predetermined level is selected as a target for treatment of the hyperproliferative disease. Methods of treating hyperproliferative diseases, monoclonal antibodies and pharmaceutical compositions are also disclosed.

## Claims

### Claim 1

A method of alleviating the progression of an ErbB-family expressing cancer in a subject in need thereof, the method comprising:
(a) administering a therapeutically effective amount of a first antibody or fragment thereof having the complementarity-determining regions (CDRs) of the monocloncal antibody deposit number CNCM I-4292 (Clone No. 551.6.103), deposited at the Collection Nationale De Cultures De Microorganismes (CNCM); and
(b) administering a therapeutically effective amount of a second antibody or fragment thereof having the CDRs of the monoclonal antibody deposit number CNCM I-4291 (Clone No. 898.47), deposited at CNCM, thereby alleviating the progression of an ErbB-family expressing cancer in said subject.

### Claim 2 (depends on 1)

The method of claim 1, further comprising administering to said subject a chemotherapeutic agent.

### Claim 3 (depends on 1)

The method of claim 1, wherein said cancer is a pancreatic cancer.

### Claim 4 (depends on 1)

The method of claim 1, wherein said cancer is a lung cancer.

### Claim 5 (depends on 1)

The method of claim 1, wherein said cancer is selected from the group consisting of breast cancer, ovarian cancer, epidermoid cancer and prostate cancer.

### Claim 6 (depends on 1)

The method of claim 1, wherein said subject is selected having increased levels of TGFα and HB-EGF in a biological sample comprising a fluid and/or cancer cells as compared to a control sample obtained from a healthy subject.
