# US 2014/0193415 A1 · Bispecific anti-egfr/anti igf-1r antibodies

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 2014/0193415 A1
- Document ID: US20140193415A1
- Status: Published application
- Kind: A1
- Application number: 14/220,952
- Filed: 2014-03-20
- Published: 2014-07-10
- Earliest claimed: 2011-09-23
- Assignees: Roche Glycart AG
- Applicants: Roche Glycart AG
- Inventors: Ralf Hosse; Christian Klein; Ekkehard Moessner; Juergen Michael Schanzer; Cuiying Shao; Lei Shi; Pablo Umana; Peng Wang; Katharina Wartha
- Web page: https://patentgrep.com/patent/US20140193415A1

## CPC

- C07K 16/2863: {against receptors for growth factors, growth regulators}
- A61P 35/00: Antineoplastic agents
- C07K 2317/21: from primates, e.g. man
- C07K 2317/31: multispecific
- C07K 2317/41: Glycosylation, sialylation, or fucosylation
- C07K 2317/55: Fab or Fab'
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2319/21: containing a His-tag
- C07K 2319/41: containing a Myc-tag
- C07K 2319/43: containing a FLAG-tag
- 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

## Abstract

The present invention relates to bispecific anti-EGFR/anti IGF-1R antibodies, methods for their production, pharmaceutical compositions containing said antibodies, and uses thereof.

## Claims

### Claim 1

A bispecific antibody that binds to human EGFR and human IGF-1R comprising a first antigen-binding site that binds to human EGFR and a second antigen-binding site that binds to human IGF-1R,
i) the first antigen-binding site comprises in the heavy chain variable domain a CDR1 of SEQ ID NO:1, a CDR2 of SEQ ID NO:2, and a CDR3 of SEQ ID NO:3, and in the light chain variable domain a CDR1 of SEQ ID NO:4, a CDR2 of SEQ ID NO:5, and a CDR3 of SEQ ID NO:6; and
ii) the second antigen-binding site is a modified antigen-binding site based on the heavy chain variable domain comprising a CDR1 of SEQ ID NO:9, a CDR2 of SEQ ID NO:10, and a CDR3 of SEQ ID NO:11; and
on the light chain variable domain comprising a CDR1 of SEQ ID NO: 12, a CDR2 of SEQ ID NO:13, and a CDR3 of SEQ ID NO:14;
wherein the modified second antigen-binding site comprises one more modifications in one or more of the CDRs; and
wherein the modified second antigen binding site has an at least 10-fold increased KD value of the binding affinity for binding to human IGF-1R compared to the unmodified second antigen binding site.

### Claim 2

A bispecific antibody that binds to human EGFR and human IGF-1R comprising a first antigen-binding site that binds to human EGFR and a second antigen-binding site that binds to human IGF-1R, characterized in that
i) the first antigen-binding site comprises in the heavy chain variable domain a CDR1 of SEQ ID NO: 1, a CDR2 of SEQ ID NO: 2, and a CDR3 of SEQ ID NO:3, and in the light chain variable domain a CDR1 of SEQ ID NO: 4, a CDR2 of SEQ ID NO:5, and a CDR3 of SEQ ID NO:6; and
ii) a) the second antigen-binding site comprises in the heavy chain variable domain a CDR1 of SEQ ID NO:17, a CDR2 of SEQ ID NO:18, and a CDR3 of SEQ ID NO:19, and in the light chain variable domain a CDR1 of SEQ ID NO:20, a CDR2 of SEQ ID NO:21, and a CDR3 of SEQ ID NO:22;
b) the second antigen-binding site comprises in the heavy chain variable domain a CDR1 of SEQ ID NO:25, a CDR2 of SEQ ID NO:26, and a CDR3 of SEQ ID NO:27, and in the light chain variable domain a CDR1 of SEQ ID NO:28, a CDR2 of SEQ ID NO:29, and a CDR3 of SEQ ID NO:30;
c) the second antigen-binding site comprises in the heavy chain variable domain a CDR1 of SEQ ID NO:33, a CDR2 of SEQ ID NO:34, and a CDR3 of SEQ ID NO:35, and in the light chain variable domain a CDR1 of SEQ ID NO:36, a CDR2 of SEQ ID NO:37, and a CDR3 of SEQ ID NO:38;
d) the second antigen-binding site comprises in the heavy chain variable domain a CDR1 of SEQ ID NO:41, a CDR2 of SEQ ID NO:42, and a CDR3 of SEQ ID NO:43, and in the light chain variable domain a CDR1 of SEQ ID NO:44, a CDR2 of SEQ ID NO:45, and a CDR3 of SEQ ID NO:46; or
e) the second antigen-binding site comprises in the heavy chain variable domain a CDR1 of SEQ ID NO:49, a CDR2 of SEQ ID NO:50, and a CDR3 of SEQ ID NO:51, and in the light chain variable domain a CDR1 of SEQ ID NO:52, a CDR2 of SEQ ID NO:53, and a CDR3 of SEQ ID NO:54.

### Claim 3 (depends on 1, 2)

The bispecific antibody according to claims 1 to 2, characterized in that
i) the first antigen-binding site comprises a heavy chain variable domain VH of SEQ ID NO: 7, and a light chain variable domain VL of SEQ ID NO: 8;
ii) a) the second antigen-binding site comprises a heavy chain variable domain VH of SEQ ID NO: 23, and a light chain variable domain VL of SEQ ID NO: 24;
b) the second antigen-binding site comprises a heavy chain variable domain VH of SEQ ID NO: 31, and a light chain variable domain VL of SEQ ID NO: 32;
c) the second antigen-binding site comprises a heavy chain variable domain VH of SEQ ID NO: 39, and a light chain variable domain VL of SEQ ID NO: 40;
d) the second antigen-binding site comprises a heavy chain variable domain VH of SEQ ID NO: 47, and a light chain variable domain VL of SEQ ID NO: 48; or
e) the second antigen-binding site comprises a heavy chain variable domain VH of SEQ ID NO: 55, and a light chain variable domain VL of SEQ ID NO: 56.

### Claim 4 (depends on 1, 2, 3)

The bispecific antibody according to any one of claims 1 to 3, characterized in that said antibody is bivalent, trivalent or tetravalent.

### Claim 5 (depends on 1, 2, 3, 4)

The bispecific antibody according to any one of claims 1 to 4, characterized in that said antibody is glycosylated with a sugar chain at Asn297 whereby the amount of fucose within said sugar chain is 65% or lower.

### Claim 6 (depends on 1, 2, 3, 4, 5)

A pharmaceutical formulation comprising a bispecific antibody according to claims 1 to 5.

### Claim 7 (depends on 1, 2, 3, 4, 5)

A bispecific antibody according to any one of claims 1 to 5 for use in the treatment of cancer.

### Claim 8 (depends on 1, 2, 3, 4, 5)

Use of a bispecific antibody according to claims 1 to 5 for the manufacture of a medicament for the treatment of cancer.

### Claim 9 (depends on 1, 2, 3, 4, 5)

A method of treatment of patient suffering from cancer by administering a bispecific antibody according to claims 1 to 5 to a patient in the need of such treatment.

### Claim 10 (depends on 1, 2, 3, 4, 5)

Nucleic acid encoding a bispecific antibody according to claims 1 to 5.

### Claim 11 (depends on 1, 2, 3, 4, 5, 10)

Expression vectors characterized by comprising a nucleic acid according to claim 10 for the expression of a bispecific antibody according to claims 1 to 5 in a host cell.

### Claim 12 (depends on 11)

Host cell comprising an expression vector according to claim 11.

### Claim 13 (depends on 1, 2, 3, 4, 5, 10)

Method for the production of a bispecific antibody according to claims 1 to 5, characterized by expressing a nucleic acid according to claim 10 in a host cell and recovering said bispecific antibody from said cell or the cell culture supernatant.