# US 7,612,178 B2 · Anti-IGF-1R antibodies and uses thereof

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- Number: US 7,612,178 B2
- Document ID: US7612178B2
- Status: Granted
- Kind: B2
- Application number: 11/727,887
- Filed: 2007-03-28
- Published: 2007-10-18
- Granted: 2009-11-03
- Earliest claimed: 2006-03-28
- Assignees: Biogen Idec MA Inc.
- Inventors: Kandasamy Hariharan; Scott Glaser; Ellen Garber; Christilyn Graff; Christopher L. Reyes; Stephen Demarest
- Web page: https://patentgrep.com/patent/US7612178B2

## CPC

- C07K 16/2863: {against receptors for growth factors, growth regulators}
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 35/04: specific for metastasis
- 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 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/52: Constant or Fc region; Isotype
- C07K 2317/524: CH2 domain
- C07K 2317/53: Hinge
- C07K 2317/55: Fab or Fab'
- 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 2317/77: Internalization into the cell
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/00: Fusion polypeptide
- 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)

## Abstract

The invention relates to antibodies which bind to insulin like growth factor receptor-1 (IGF-1R) and uses thereof, in particular in the diagnosis and treatment of cancer. Specific human and murine monoclonal antibodies which inhibit IGF-1R-mediated pro-survival and tumor proliferation pathways, and variants, fragments, and derivatives thereof are provided. Also provided are specific human and murine monoclonal antibodies which block the ability of the ligands, insulin like growth factor 1 (IGF-1) and insulin like growth factor 2 (IGF-2) to bind to IGF-1R, as well as fragments, variants and derivatives of such antibodies. The invention also includes polynucleotides encoding the above antibodies or fragments, variants or derivatives thereof, as well as vectors and host cells comprising such polynucleotides. The invention further includes methods of diagnosing and treating cancer using antibodies of the invention.

## Claims

### Claim 1

An isolated antibody or antigen-binding fragment thereof wherein said antibody is M13-C06.G4.P.agly or a fragment thereof which specifically binds to IGF-1R produced by Chinese Hamster Ovary (CHO) cells deposited under American Type Culture Collection (ATCC) Deposit Number PTA-7444.

### Claim 2

An isolated antibody or antigen-binding fragment thereof, wherein said antibody or fragment thereof comprises an antigen binding domain identical to that of a monoclonal Fab antibody fragment of M13-C06.G4.P.agly produced by Chinese Hamster Ovary (CHO) cells deposited under American Type Culture Collection (ATCC) Deposit Number PTA-7444.

### Claim 3

An isolated antibody or fragment thereof which specifically binds to IGF-1R, wherein the VH of said antibody or fragment thereof comprises the amino acid sequence of SEQ ID NO: 14.

### Claim 4

An isolated antibody or fragment thereof which specifically binds to IGF-1R, wherein the VL of said antibody or fragment thereof comprises the amino acid sequence of SEQ ID NO: 78.

### Claim 5

An isolated antibody or fragment thereof which specifically binds to IGF-1R, wherein the VH and VL of said antibody or fragment thereof comprise, respectively, the amino acid sequences of SEQ ID NO: 14 and SEQ ID NO: 78.

### Claim 6

An isolated antibody or fragment thereof which specifically binds to IGF-1R, wherein the VH of said antibody or fragment thereof comprises the VH-CDR1, VH-CDR2, and VH-CDR3 amino acid sequences of SEQ ID NOs: 15, 16, and 17.

### Claim 7

An isolated antibody or fragment thereof which specifically binds to IGF-1R, wherein the VL of said antibody or fragment thereof comprises the VL-CDR1, VL-CDR2, and VL-CDR3 amino acid sequences of SEQ ID NOs: 79, 80, and 81.

### Claim 8 (depends on 1)

A method of producing the antibody or fragment thereof of claim 1, comprising culturing a host cell expressing said antibody or fragment thereof, and recovering said antibody or fragment thereof.

### Claim 9 (depends on 2)

A method of producing the antibody or fragment thereof of claim 2, comprising culturing a host cell expressing said antibody or fragment thereof, and recovering said antibody or fragment thereof.

### Claim 10 (depends on 3)

A method of producing the antibody or fragment thereof of claim 3, comprising culturing a host cell expressing said antibody or fragment thereof, and recovering said antibody or fragment thereof.

### Claim 11 (depends on 4)

A method of producing the antibody or fragment thereof of claim 4, comprising culturing a host cell expressing said antibody or fragment thereof, and recovering said antibody or fragment thereof.

### Claim 12 (depends on 5)

A method of producing the antibody or fragment thereof of claim 5, comprising culturing a host cell expressing said antibody or fragment thereof, and recovering said antibody or fragment thereof.

### Claim 13 (depends on 6)

A method of producing the antibody or fragment thereof of claim 6, comprising culturing a host cell expressing said antibody or fragment thereof, and recovering said antibody or fragment thereof.

### Claim 14 (depends on 7)

A method of producing the antibody or fragment thereof of claim 7 comprising culturing a host cell expressing said antibody or fragment thereof, and recovering said antibody or fragment thereof.

### Claim 15

An isolated antibody comprising the VH-CDR1, VH-CDR2, VH-CDR3, VL-CDR1, VL-CDR2, and VL-CDR3 amino acid sequences of SEQ ID NOs: 15, 16, 17, 79, 80, and 81.

### Claim 16 (depends on 15)

A method of producing the antibody of claim 15 comprising culturing a host cell expressing said antibody and recovering said antibody or fragment thereof.
