# US 2024/0199747 A1 · Erbb-2 and erbb3 binding bispecific antibodies for use in the treatment of cells that have an nrg1 fusion gene

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

- Number: US 2024/0199747 A1
- Document ID: US20240199747A1
- Status: Published application
- Kind: A1
- Application number: 18/449,460
- Filed: 2023-08-14
- Published: 2024-06-20
- Earliest claimed: 2017-03-31
- Applicants: Merus N.V.
- Inventors: Mark THROSBY; Cecilia Anna Wihelmina GEUIJEN; David Andre Baptiste MAUSSANG-DETAILLE; Ton LOGTENBERG
- Web page: https://patentgrep.com/patent/US20240199747A1

## CPC

- C07K 16/2863: {against receptors for growth factors, growth regulators}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- C07K 16/32: against translation products of oncogenes
- C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/21: from primates, e.g. man
- C07K 2317/31: multispecific
- C07K 2317/52: Constant or Fc region; Isotype
- 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 invention relates to the field of antibodies. In particular it relates to the field of therapeutic (human) antibodies for the treatment of ErbB-2/ErbB-3 positive cells. More in particular it relates to treating of cells comprising an NRG1 fusion gene comprising at least a portion of the NRG1-gene fused to a sequence from a different chromosomal location.

## Claims

### Claim 1

A method of treating an individual that has an ErbB-2 and ErbB-3 positive cell, which cell comprises an NRG1 fusion gene comprising at least a portion of the NRG1-gene fused to a sequence from a different chromosomal location, the method comprising administering to the individual a bispecific antibody that comprises a first antigen-binding site that can bind an extracellular part of ErbB-2 and a second antigen-binding site that can bind an extracellular part of ErbB-3.

### Claim 2 (depends on 1)

The method of claim 1, wherein the NRG1 fusion gene comprises at least the 3′ end of the NRG1-gene fused to a 5′ sequence from a different chromosomal location.

### Claim 3 (depends on 1)

The method of claim 1, wherein the cell is a cancer cell.

### Claim 4 (depends on 3)

The method of claim 3 wherein the cancer cell is associated with an NRG1-fusion.

### Claim 5 (depends on 3)

The method of claim 3, wherein the cancer cell is driven by NRG1-fusion.

### Claim 6 (depends on 1)

The method of claim 1, wherein the cell is a breast cancer cell, an ovarian cancer cell, a lung cancer cell, such as non-small cell lung cancer, or a metastasis thereof.

### Claim 7

A method of treating an individual that has an ErbB-2 and ErbB-3 positive tumor, wherein cells of the tumor express an NRG1 fusion gene comprising at least the 3′ end of the NRG1-gene fused to a 5′ sequence from a different chromosomal location, the method comprising administering to the individual a bispecific antibody that comprises a first antigen-binding site that can bind an extracellular part of ErbB-2 and a second antigen-binding site that can bind an extracellular part of ErbB-3.

### Claim 8 (depends on 7)

The antibody for use method of claim 7, wherein the tumor is breast cancer, an ovarian cancer, a lung cancer, such as non-small cell lung cancer, or a metastasis thereof.

### Claim 9 (depends on 1)

The antibody for use method of any of the preceding claim 1,
wherein the NRG1-fusion gene expresses a protein that comprises an NRG1 EGF-like domain.

### Claim 10 (depends on 1)

The antibody for use method of any of the preceding claim 1,
wherein the NRG-fusion is a fusion of NRG1 and a gene on human chromosome 8.

### Claim 11 (depends on 10)

The antibody for use method of claim 10, wherein the gene on human chromosome 8 encodes an excreted protein or a cellular membrane associated protein.

### Claim 12 (depends on 1)

The antibody for use method of any of the preceding claim 1,
wherein the NRG1 fusion gene is a fusion of the 3′ end of the NRG1-gene with the 5′ sequence of one of the genes selected from the group consisting of CD74; DOC4; TNFRSF10B; CLU;
VAMP2; SLC3A2; RBPMS; WRN; SDC4; KIF13B; SLECA2; PDE7A; ATP1B1; CDK1;
BMPRIB; MCPH1 and RAB2IL1.

### Claim 13 (depends on 1)

The method of claim 1, wherein the cell is of an epithelial origin.

### Claim 14 (depends on 1)

The method of claim 1, wherein the individual has undergone a therapy that targeted towards EGFR inhibition, preferably with an EGFR binding antibody.

### Claim 15 (depends on 1)

The method of claim 1, wherein the ErbB-1 cell-surface receptor density, ErbB-2 cell-surface receptor density, ErbB-3 cell-surface receptor density, ErbB-4 cell-surface receptor density, or a combination thereof on the cell is determined.

### Claim 16 (depends on 1)

The method of claim 1, wherein the cell or tumor has less than 400,000 ErbB-1 cell-surface receptors per cell.

### Claim 17 (depends on 1)

The method of claim 1, further comprising administering to the individual an ErbB-1 inhibitor.

### Claim 18 (depends on 1)

The method of claim 1, wherein said first antigen-binding site can bind domain I of ErbB-2 and said second antigen-binding site can bind domain III of ErbB-3.

### Claim 19 (depends on 18)

The method of claim 18, wherein
i) at least the CDR1, CDR2 and CDR3 sequences of an ErbB-2 specific heavy chain variable region selected from the group consisting of MF2926, MF2930, MF1849; MF2973, MF3004, MF3958, MF2971, MF3025, MF2916, MF3991, MF3031, MF2889, MF2913, MF1847, MF3001, MF3003 and MF1898 or wherein CDR sequences that differ in at most 3 amino acids
ii) at least the CDR1, CDR2 and CDR3 sequences of an ErbB-3 specific heavy chain variable region selected from the group consisting of MF3178; MF3176; MF3163; MF3099; MF3307; MF6055; MF6056; MF6057; MF6058; MF6059; MF6060; MF6061; MF6062; MF6063; MF6064; MF6065; MF6066; MF6067; MF6068; MF6069; MF6070; MF6071; MF6072; MF6073 and MF6074, or wherein said antibody comprises CDR sequences that differ in at most 3 amino acids,
i) an ErbB-2 specific heavy chain variable region sequence selected from the group consisting of the heavy chain variable region sequences of MF2926, MF2930, MF1849; MF2973, MF3004, MF3958, MF2971, MF3025, MF2916, MF3991, MF3031, MF2889, MF2913, MF1847, MF3001, MF3003 and MF1898, or wherein a heavy chain variable region sequence that differs in at most 15 amino acids from the heavy chain variable region sequences of MF2926, MF2930, MF1849; MF2973, MF3004, MF3958, MF2971, MF3025, MF2916, MF3991, MF3031, MF2889, MF2913, MF1847, MF3001, MF3003 or MF1898; and/or
ii) an ErbB-3 specific heavy chain variable region sequence selected from the group consisting of the heavy chain variable region sequences of MF3178; MF3176; MF3163; MF3099; MF3307; MF6055; MF6056; MF6057; MF6058; MF6059; MF6060; MF6061; MF6062; MF6063; MF6064; MF6065; MF6066; MF6067; MF6068; MF6069; MF6070; MF6071; MF6072; MF6073 and MF6074, or wherein a heavy chain variable region sequence that differs in at most 15 amino acids from the heavy chain variable region sequences of MF3178; MF3176; MF3163; MF3099; MF3307; MF6055; MF6056; MF6057; MF6058; MF6059; MF6060; MF6061; MF6062; MF6063; MF6064; MF6065; MF6066; MF6067; MF6068; MF6069; MF6070; MF6071; MF6072; MF6073 or MF6074.

### Claim 20 (depends on 18)

The method of claim 18, wherein the antibody comprises at least the CDR1, CDR2 and CDR3 sequences of the ErbB 2 specific heavy chain variable region MF3958 and the antibody comprises at least the CDR1, CDR2 and CDR3 sequences of the ErbB 3 specific heavy chain variable region MF3178.

### Claim 21 (depends on 1)

The method of claim 1, wherein the variable domain that comprises said first antigen binding site and the variable domain that comprises said second antigen binding site comprise a light chain variable region comprising the IgVK1-39 gene segment.