# US 7,744,881 B2 · Human DR4 antibodies and uses thereof

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- Number: US 7,744,881 B2
- Document ID: US7744881B2
- Status: Granted
- Kind: B2
- Application number: 11/819,575
- Filed: 2007-06-28
- Published: 2008-09-25
- Granted: 2010-06-29
- Earliest claimed: 2007-06-28
- Assignees: Genentech, Inc.
- Inventors: Anan Chuntharapai; Kyung Jin Kim
- Web page: https://patentgrep.com/patent/US7744881B2

## CPC

- C07K 16/2878: {against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95}
- 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 2317/21: from primates, e.g. man
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/75: Agonist effect on antigen
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- G01N 2510/00: Detection of programmed cell death, i.e. apoptosis
- 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)
- 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

Human Death Receptor 4 (DR4) antibodies are provided. The human DR4 antibodies may be included in pharmaceutical compositions, articles of manufacture, or kits. Methods of treatment and diagnosis using the DR4 antibodies are also provided.

## Claims

### Claim 1

A method of inducing apoptosis in mammalian cancer cells comprising exposing mammalian cancer cells expressing DR4 receptor to a therapeutically effective amount of an isolated, monoclonal human anti-DR4 receptor antibody that inhibits binding of Apo-2 ligand to the DR4 receptor, induces apoptosis upon binding to the DR4 receptor and binds to the same DR4 receptor epitope to which the monoclonal antibody produced by the hybridoma deposited as ATCC PTA-3359 binds, wherein said antibody binds to the DR4 receptor with a binding affinity of at least 108 M−1 to 1012 M−1.

### Claim 2

A method of inducing apoptosis in mammalian cancer cells comprising exposing mammalian cells expressing DR4 receptor to a therapeutically effective amount of an isolated, monoclonal human anti-DR4 receptor antibody that inhibits binding of Apo-2 ligand to the DR4 receptor, induces apoptosis upon binding to the DR4 receptor and binds to the same DR4 receptor epitope to which the monoclonal antibody produced by the hybridoma deposited as ATCC PTA-3360 binds, wherein said antibody binds to the DR4 receptor with a binding affinity of at least 108 M−1 to 1012 M−1.

### Claim 3

A method of inducing apoptosis in mammalian cancer cells comprising exposing mammalian cancer cells expressing DR4 receptor to a therapeutically effective amount of an isolated, monoclonal human anti-DR4 receptor antibody that inhibits binding of Apo-2 ligand to the DR4 receptor, induces apoptosis upon binding to the DR4 receptor and binds to the same DR4 receptor epitope to which the monoclonal antibody produced by the hybridoma deposited as ATCC PTA-3361 binds, wherein said antibody binds to the DR4 receptor with a binding affinity of at least 108 M−1 to 1012 M−1.

### Claim 4 (depends on 1)

The method of claim 1, wherein the isolated monoclonal human anti-DR4 receptor antibody is linked to one or more non-proteinaceous polymers selected from the group consisting of polyethylene glycol, polypropylene glycol, and polyoxyalkylene.

### Claim 5 (depends on 1)

The method of claim 1, wherein the isolated monoclonal human anti-DR4 receptor antibody is linked to a cytotoxic agent or enzyme.

### Claim 6 (depends on 1)

The method of claim 1, wherein the isolated monoclonal human anti-DR4 receptor antibody is linked to a radioisotope, fluorescent compound or chemiluminescent compound.

### Claim 7 (depends on 1)

The method of claim 1, wherein the isolated monoclonal human anti-DR4 receptor antibody is glycosylated.

### Claim 8 (depends on 1)

The method of claim 1, wherein the isolated monoclonal human anti-DR4 receptor antibody is unglycosylated.

### Claim 9

A method of inducing apoptosis in mammalian cancer cells comprising exposing mammalian cancer cells expressing DR4 receptor to a therapeutically effective amount of an isolated anti-DR4 receptor monoclonal antibody, wherein the anti-DR4 receptor antibody is produced by the hybridoma deposited as ATCC PTA-3359.

### Claim 10 (depends on 9)

The method of claim 9, wherein the anti-DR4 receptor antibody is linked to one or more non-proteinaceous polymers selected from the group consisting of polyethylene glycol, polypropylene glycol, and polyoxyalkylene.

### Claim 11 (depends on 9)

The method of claim 9, wherein the anti-DR4 receptor antibody is linked to a cytotoxic agent or enzyme.

### Claim 12 (depends on 9)

The method of claim 9, wherein the anti-DR4 receptor antibody is linked to a radioisotope, fluorescent compound or chemiluminescent compound.

### Claim 13 (depends on 9)

The method of claim 9, wherein the anti-DR4 receptor antibody is glycosylated.

### Claim 14 (depends on 9)

The method of claim 9, wherein the anti-DR4 receptor antibody is unglycosylated.

### Claim 15 (depends on 2)

The method of claim 2, wherein the isolated monoclonal human anti-DR4 receptor antibody is linked to one or more non-proteinaceous polymers selected from the group consisting of polyethylene glycol, polypropylene glycol, and polyoxyalkylene.

### Claim 16 (depends on 2)

The method of claim 2, wherein the isolated monoclonal human anti-DR4 receptor antibody is linked to a cytotoxic agent or enzyme.

### Claim 17 (depends on 2)

The method of claim 2, wherein the isolated monoclonal human anti-DR4 receptor antibody is linked to a radioisotope, fluorescent compound or chemiluminescent compound.

### Claim 18 (depends on 2)

The method of claim 2, wherein the isolated monoclonal human anti-DR4 receptor antibody is glycosylated.

### Claim 19 (depends on 2)

The method of claim 2, wherein the isolated monoclonal human anti-DR4 receptor antibody is unglycosylated.

### Claim 20

A method of inducing apoptosis in mammalian cancer cells comprising exposing mammalian cancer cells expressing DR4 receptor to a therapeutically effective amount of an isolated anti-DR4 receptor monoclonal antibody, wherein the anti-DR4 receptor antibody is produced by the hybridoma deposited as ATCC PTA-3360.

### Claim 21 (depends on 20)

The method of claim 20, wherein the anti-DR4 receptor antibody is linked to one or more non-proteinaceous polymers selected from the group consisting of polyethylene glycol, polypropylene glycol, and polyoxyalkylene.

### Claim 22 (depends on 20)

The method of claim 20, wherein the anti-DR4 receptor antibody is linked to a cytotoxic agent or enzyme.

### Claim 23 (depends on 20)

The method of claim 20, wherein the anti-DR4 receptor antibody is linked to a radioisotope, fluorescent compound or chemiluminescent compound.

### Claim 24 (depends on 20)

The method of claim 20, wherein the anti-DR4 receptor antibody is glycosylated.

### Claim 25 (depends on 20)

The method of claim 20, wherein the anti-DR4 receptor antibody is unglycosylated.

### Claim 26 (depends on 3)

The method of claim 3, wherein the isolated monoclonal human anti-DR4 receptor antibody is linked to one or more non-proteinaceous polymers selected from the group consisting of polyethylene glycol, polypropylene glycol, and polyoxyalkylene.

### Claim 27 (depends on 3)

The method of claim 3, wherein the isolated monoclonal human anti-DR4 receptor antibody is linked to a cytotoxic agent or enzyme.

### Claim 28 (depends on 3)

The method of claim 3, wherein the isolated monoclonal human anti-DR4 receptor antibody is linked to a radioisotope, fluorescent compound or chemiluminescent compound.

### Claim 29 (depends on 3)

The method of claim 3, wherein the isolated monoclonal human anti-DR4 receptor antibody is glycosylated.

### Claim 30 (depends on 3)

The method of claim 3, wherein the isolated monoclonal human anti-DR4 receptor antibody is unglycosylated.

### Claim 31

A method of inducing apoptosis in mammalian cancer cells comprising exposing mammalian cancer cells expressing DR4 receptor to a therapeutically effective amount of an isolated anti-DR4 receptor monoclonal antibody, wherein the anti-DR4 receptor antibody is produced by the hybridoma deposited as ATCC PTA-3361.

### Claim 32 (depends on 31)

The method of claim 31, wherein the anti-DR4 receptor antibody is linked to one or more non-proteinaceous polymers selected from the group consisting of polyethylene glycol, polypropylene glycol, and polyoxyalkylene.

### Claim 33 (depends on 31)

The method of claim 31, wherein the anti-DR4 receptor antibody is linked to a cytotoxic agent or enzyme.

### Claim 34 (depends on 31)

The method of claim 31, wherein the anti-DR4 receptor antibody is linked to a radioisotope, fluorescent compound or chemiluminescent compound.

### Claim 35 (depends on 31)

The method of claim 31, wherein the anti-DR4 receptor antibody is glycosylated.

### Claim 36 (depends on 31)

The method of claim 31, wherein the anti-DR4 receptor antibody is unglycosylated.