# US 2013/0156772 A1 · Bispecific Anti ErbB1 / Anti cMet Antibodies

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- Number: US 2013/0156772 A1
- Document ID: US20130156772A1
- Status: Published application
- Kind: A1
- Application number: 13/774,192
- Filed: 2013-02-22
- Published: 2013-06-20
- Earliest claimed: 2009-04-07
- Assignees: Roche Glycart AG
- Inventors: Birgit Bossenmaier; Ulrich Brinkmann; Christian Klein; Gerhard Niederfellner; Wolfgang Schaefer; Juergen Michael Schanzer; Claudio Sustmann; Pablo Umana
- Web page: https://patentgrep.com/patent/US20130156772A1

## CPC

- A61P 35/00: Antineoplastic agents
- C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies}
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/32: against translation products of oncogenes
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/31: multispecific
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/55: Fab or Fab'
- C07K 2317/56: variable (Fv) region, i.e. VH and/or VL
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/622: Single chain antibody (scFv)
- 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
- 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)
- 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 present invention relates to bispecific antibodies against human ErbB-1 and against human c-Met, methods for their production, pharmaceutical compositions containing the antibodies, and uses thereof.

## Claims

### Claim 1

A bispecific antibody that specifically binds to human ErbB-1 and human c-Met comprising a first antigen-binding site that specifically binds to human ErbB-1 and a second antigen-binding site that specifically binds to human c-Met, wherein the bispecific antibody causes an increase in internalization of c-Met on OVCAR-8 cells of no more than 15% when measured after 2 hours of OVCAR-8 cell-antibody incubation as measured by a flow cytometry assay as compared to internalization of c-Met on OVCAR-8 cells in the absence of the bispecific antibody.

### Claim 2 (depends on 1)

The bispecific antibody according to claim 1 wherein the antibody is a bivalent or trivalent bispecific antibody comprising one or two antigen-binding sites that specifically bind to human ErbB-1 and a third antigen-binding site that specifically binds to human c-Met.

### Claim 3 (depends on 2)

The antibody according to claim 2 comprising
a) a full length antibody that specifically binds to ErbB-1 consisting of two antibody heavy chains and two antibody light chains; and
b) one single chain Fab fragment that specifically binds to human c-Met,
wherein the single chain Fab fragment under b) is fused to the full length antibody under a) via a peptide connector to the C- or N-terminus of the heavy or light chain of the full length antibody.

### Claim 4

A bispecific antibody that specifically binds to human ErbB-1 and human c-Met comprising a first antigen-binding site that specifically binds to human ErbB-1 and a second antigen-binding site that specifically binds to human c-Met, wherein
i) the first antigen-binding site comprises in the heavy chain variable domain a CDR3 region with the amino acid sequence of SEQ ID NO: 17, a CDR2H region with the amino acid sequence of SEQ ID NO: 18, and a CDR1H region with the amino acid sequence of SEQ ID NO:19, and in the light chain variable domain a CDR3L region with the amino acid sequence of SEQ ID NO: 20, a CDR2L region with the amino acid sequence of SEQ ID NO:21, and a CDR1L region with the amino acid sequence of SEQ ID NO:58 or a CDR1L region with the amino acid sequence of SEQ ID NO:22; and
the second antigen-binding site comprises in the heavy chain variable domain a CDR3H region with the amino acid sequence of SEQ ID NO: 30, a CDR2H region with the amino acid sequence of, SEQ ID NO: 31, and a CDR1H region with the amino acid sequence of SEQ ID NO: 32, and in the light chain variable domain a CDR3L region with the amino acid sequence of SEQ ID NO: 33, a CDR2L region with the amino acid sequence of SEQ ID NO: 34, and a CDR1L region with the amino acid sequence of SEQ ID NO: 35.
ii) the first antigen-binding site comprises in the heavy chain variable domain a CDR3H region with the amino acid sequence of SEQ ID NO: 23, a CDR2H region with the amino acid sequence of SEQ ID NO: 24, and a CDR1H region with the amino acid sequence of SEQ ID NO:25, and in the light chain variable domain a CDR3L region with the amino acid sequence of SEQ ID NO: 26, a CDR2L region with the amino acid sequence of SEQ ID NO:27, and a CDR1L region with the amino acid sequence of SEQ ID NO:28 or a CDR1L region with the amino acid sequence of SEQ ID NO:29; and
the second antigen-binding site comprises in the heavy chain variable domain a CDR3H region with the amino acid sequence of SEQ ID NO: 30, a CDR2H region with the amino acid sequence of, SEQ ID NO: 31, and a CDR1H region with the amino acid sequence of SEQ ID NO: 32, and in the light chain variable domain a CDR3L region with the amino acid sequence of SEQ ID NO: 33, a CDR2L region with the amino acid sequence of SEQ ID NO: 34, and a CDR1L region with the amino acid sequence of SEQ ID NO: 35.

### Claim 5 (depends on 4)

The bispecific antibody according to claim 4 characterized in that
i) the first antigen-binding site specifically binding to ErbB-1 comprises as heavy chain variable domain the sequence of SEQ ID NO: 1, and as light chain variable domain the sequence of SEQ ID NO: 2; and
the second antigen-binding site specifically binding to c-Met comprises as heavy chain variable domain the sequence of SEQ ID NO: 5, and as light chain variable domain the sequence of SEQ ID NO: 6; or
ii) the first antigen-binding site specifically binding to ErbB-1 comprises as heavy chain variable domain the sequence of SEQ ID NO: 3, and as light chain variable domain the sequence of SEQ ID NO: 4; and
the second antigen-binding site specifically binding to c-Met comprises as heavy chain variable domain the sequence of SEQ ID NO: 5, and as light chain variable domain the sequence of SEQ ID NO: 6.

### Claim 6 (depends on 1)

The bispecific antibody according to claim 1 wherein the antibody comprises a constant region of IgG1 or IgG3 subclass.

### Claim 7 (depends on 5)

The bispecific antibody according to claim 5 wherein the antibody comprises a constant region of IgG1 or IgG3 subclass.

### Claim 8 (depends on 1)

The bispecific antibody according to claim 1 wherein the antibody is glycosylated with a sugar chain at Asn297 wherein the amount of fucose within the sugar chain is 65% or lower.

### Claim 9 (depends on 5)

The bispecific antibody according to claim 5 wherein the antibody is glycosylated with a sugar chain at Asn297 wherein the amount of fucose within the sugar chain is 65% or lower.

### Claim 10 (depends on 1)

A nucleic acid encoding a bispecific antibody according to claim 1.

### Claim 11 (depends on 5)

A nucleic acid encoding a bispecific antibody according to claim 5.

### Claim 12 (depends on 1)

A method of treatment of a patient suffering from cancer by administering an effective amount of a bispecific antibody according to claim 1 to a patient in the need of such treatment.

### Claim 13 (depends on 5)

A method of treatment of a patient suffering from cancer by administering an effective amount of a bispecific antibody according to claim 5 to a patient in the need of such treatment.