# US 7,411,045 B2 · Autocrine growth factor receptor antibodies and methods

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- Number: US 7,411,045 B2
- Document ID: US7411045B2
- Status: Granted
- Kind: B2
- Application number: 10/298,540
- Filed: 2002-11-19
- Published: 2003-05-29
- Granted: 2008-08-12
- Earliest claimed: 2002-11-19
- Assignees: A&G Pharmaceutical, Inc.
- Inventors: Ginette Serrero; Le Sun
- Web page: https://patentgrep.com/patent/US7411045B2

## CPC

- C07K 14/475: Growth factors; Growth regulators
- A61P 35/00: Antineoplastic agents
- C07K 16/22: against growth factors {; against growth regulators}
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- 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}
- G01N 33/6872: {Intracellular protein regulatory factors and their receptors, e.g. including ion channels}
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- A61K 2039/505: {comprising 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
- C12N 2799/026: where the vector is derived from a baculovirus
- 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
- 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Disclosed herein are antitumor compositions and methods of interfering with the biological activity of PC cell derived growth factor (PCDGF), anti-PCDGF receptor antibodies, fragments thereof, and methods of making anti-PCDGF receptor antibodies. The methods involve inhibiting the proliferation of tumor cells expressing the PCDGF receptor by contacting the surface of the cell with anti-PCDGF receptor antibodies. Anti-PCDGF receptor antibodies are capable of binding to the surface of a cell and interfering with the binding of PCDGF to its receptor. Also provided are compositions comprising anti-PCDGF receptor antibodies and cytotoxic molecules (e.g., toxins, oncotoxins, mitotoxins, immunotoxins, and antisense oligonucleotides).

## Claims

### Claim 1

A composition comprising an antibody or antigen binding fragment capable of binding to a PCDGF receptor and interfering with binding of PCDGF to the PCDGF receptor.

### Claim 2 (depends on 1)

The composition according to claim 1, wherein said antibody or antigen binding fragment does not bind PCDGF.

### Claim 3 (depends on 1)

The composition according to claim 1, wherein said antibody or antigen binding fragment is an anti-idiotypic antibody or antibody fragment capable of binding to an anti-PCDGF antibody.

### Claim 4 (depends on 1)

The composition according to claim 1, wherein said antibody or antigen binding fragment interferes with the biological activity of PCDGF.

### Claim 5 (depends on 1)

The composition according to claim 1, wherein said antibody or antigen binding antibody fragment reduces the proliferation of tumorigenic cells by at least about 20% in vitro.

### Claim 6 (depends on 1)

The composition according to claim 1, wherein said antibody or antigen binding antibody-fragment reduces the proliferation of tumorigenic cells by at least about 60% in vitro.

### Claim 7 (depends on 5)

The composition according to claim 5, wherein said tumorigenic cells are derived from tissue or biological fluid selected from the group consisting of blood, cerebrospinal fluid, serum, plasma, urine, nipple aspirate, liver, kidney, breast, prostate, bone, bone marrow, testes, brain, ovary, skin, or lung.

### Claim 8 (depends on 1)

The composition according to claim 1, wherein said antibody or antigen binding fragment is capable of interfering with cyclin D1 expression.

### Claim 9 (depends on 1)

The composition according to claim 1, wherein said antibody or antigen binding fragment is capable of interfering with the phosphorylation of MAP kinase.

### Claim 10 (depends on 1)

The composition according to claim 1, wherein said antibody or antigen binding fragment is produced from a hybridoma cell line selected from the group consisting of 6G8 (ATCC Accession Number PTA-5263) and 5A8 (ATCC Accession Number PTA-5594).

### Claim 11 (depends on 1)

The composition according to claim 1, wherein said antibody or antigen binding fragment is derived from an animal immunized with a material comprising an anti-PCDGF antibody.

### Claim 12 (depends on 1)

The composition according to claim 1, wherein said antibody or antigen binding fragment is derived from an animal immunized with a material comprising PCDGF.

### Claim 13 (depends on 1)

The composition according to claim 1, wherein said antibody or antigen binding fragment is derived from an animal immunized with a material comprising cells overexpressing the PCDGF receptor or cell fragments derived from cells overexpressing the PCDGF receptor.

### Claim 14 (depends on 1)

The antibody according to claim 1, wherein said antibody or antigen binding fragment is derived from an animal immunized with a material comprising an anti-PCDGF antibody produced from a hybridoma cell line selected from the group consisting of 6B3 (ATCC Accession Number PTA-5262), 6B2 (ATCC Accession Number PTA-5261), 6C12 (ATCC Accession Number PTA-5597), 5B4 (ATCC Accession Number PTA-5260), 5G6 (ATCC Accession Number PTA-5595), 4D1 (ATCC Accession Number PTA-5593), 3F8 (ATCC Accession Number PTA-5591), 3F5 (ATCC Accession Number PTA-5259), 3F4 (ATCC Accession Number PTA-5590), 3G2 (ATCC Accession Number PTA-5592), and 2A5 (ATCC Accession Number PTA-5589).

### Claim 15 (depends on 1)

The antibody according to claim 1, wherein said antibody or antigen binding fragment is derived from an animal immunized with PCDGF.

### Claim 16 (depends on 1)

The composition according to claim 1, wherein said antibody or antigen binding fragment is chimeric, humanized or from a human.

### Claim 17 (depends on 1)

The composition according to claim 1 wherein said antigen binding fragment is an Fab or F(ab′)2 fragment.

### Claim 18

A composition comprising an anti-PCDGF receptor antibody or antigen binding fragment and a cytotoxic molecule wherein said anti-PCDGF receptor antibody or antigen binding fragment is attached or capable of binding to said cytotoxic molecule.

### Claim 19 (depends on 18)

The composition of claim 18 wherein said cytotoxic molecule is selected from the group consisting of toxins, oncotoxins, mitotoxins, and immunotoxins, and antisense oligonucleotides.

### Claim 20 (depends on 18)

A composition according to claim 18 wherein said antibody or antigen binding fragment is produced from a hybridoma cell line selected from the group consisting of 6G8 (ATCC Accession Number PTA-5263) and 5A8 (ATCC Accession Number PTA-5594).

### Claim 21

A monoclonal anti-PCDGF receptor antibody or antigen binding fragment produced from a hybridoma cell line selected from the group consisting of 6G8 (ATCC Accession Number) and 5A8 (ATCC Accession Number PTA-5594).

### Claim 22

A method of making an anti-idiotypic antibody or antigen binding fragment comprising immunizing an animal with the monoclonal anti-PCDGF antibody or antigen binding fragment produced from a hybridoma cell line selected from the group consisting of 6B3 (ATCC Accession Number PTA-5262), 6B2 (ATCC Accession Number PTA-5261), 6C12 (ATCC Accession Number PTA-5597), 5B4 (ATCC Accession Number PTA-5260), 5G6 (ATCC Accession Number PTA-5595), 4D1 (ATCC Accession Number PTA-5593), 3F8 (ATCC Accession Number PTA-5591), 3F5 (ATCC Accession Number PTA-5259), 3F4 (ATCC Accession Number PTA-5590), 3G2 (ATCC Accession Number PTA-5592), and 2A5 (ATCC Accession Number PTA-5589) isolating spleen cells from said immunized animals, producing hybridomas from said spleen cells, and screening said hybridomas to identify an anti-idiotypic antibody or antibody fragment capable of binding to the surface of a cell expressing the PCDGF receptor and interfering with the binding of PCDGF to the PCDGF receptor.

### Claim 23

A method of making an anti-idiotypic antibody or antigen binding fragment comprising immunizing an animal with PCDGF, isolating spleen cells from said immunized animals, producing hybridomas from said spleen cells, and screening said hybridomas to identify an anti-idiotypic antibody or antibody fragment capable of binding to the surface of a cell expressing the PCDGF receptor and interfering with the binding of PCDGF to the PCDGF receptor.

### Claim 24

A method of making an anti-PCDGF receptor antibody or antigen binding fragment comprising immunizing an animal with cells overexpressing the PCDGF receptor or cell fragments derived from cells overexpressing the PCDGF receptor, isolating spleen cells from said immunized animals, producing hybridomas from said spleen cells, and screening said hybridomas to identify an anti-PCDGF receptor antibody or antibody fragment capable of binding to the surface of a cell expressing the PCDGF receptor and interfering with the binding of PCDGF to the PCDGF receptor.
