# US 11,299,547 B2 · CMET monoclonal binding agents, drug conjugates thereof and uses thereof

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- Number: US 11,299,547 B2
- Document ID: US11299547B2
- Status: Granted
- Kind: B2
- Application number: 16/334,326
- Filed: 2017-09-28
- Published: 2019-10-31
- Granted: 2022-04-12
- Earliest claimed: 2016-09-29
- Assignees: Mitsubishi Tanabe Pharma Corporation
- Applicants: Mitsubishi Tanabe Pharma Corporation
- Inventors: Julia Coronella; Vincent Blot; Marco Gymnopoulos; Anjuli Timmer; Ryo Fujita; Roland Newman
- Web page: https://patentgrep.com/patent/US11299547B2

## CPC

- C07K 16/2863: {against receptors for growth factors, growth regulators}
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61K 2039/505: {comprising antibodies}
- A61K 2039/54: {characterised by the route of administration}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- 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 2317/565: Complementarity determining region [CDR]
- C07K 2317/567: Framework region [FR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/77: Internalization into the cell
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- 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

Presented herein, in certain embodiments, are compositions comprising monoclonal binding agents that specifically bind to the extracellular domain of cMET and uses thereof.

## Claims

### Claim 1

A binding agent comprising:
a CDR-L1 selected from SEQ ID NOs: 1-15,
a CDR-L2 selected from SEQ ID NOs: 16-25,
a CDR-L3 selected from SEQ ID NOs: 26-36,
a CDR-H1 selected from SEQ ID NOs: 50-61,
a CDR-H2 selected from SEQ ID NOs: 62-78, and
a CDR-H3 selected from SEQ ID NOs: 79-93
wherein the binding agent specifically binds to an extracellular domain of mesenchymal epithelial transition factor (cMET).

### Claim 2 (depends on 1)

The binding agent of claim 1, wherein the binding agent is an antibody, or a binding fragment thereof.

### Claim 3 (depends on 2)

The binding agent of claim 2, which is selected from the group consisting of:
(i) a binding agent comprising
a CDR-L1 of SEQ ID NO: 1 or 2,
a CDR-L2 of SEQ ID NO: 16 or 17,
a CDR-L3 of SEQ ID NO: 26 or 27,
a CDR-H1 of SEQ ID NO: 50 or 51,
a CDR-H2 of SEQ ID NO: 62 or 53, and
a CDR-H3 of SEQ ID NO: 79 or 80;
(ii) a binding agent comprising
a CDR-L1 of SEQ ID NO: 3 or 4,
a CDR-L2 of SEQ ID NO: 18 or 19,
a CDR-L3 of SEQ ID NO: 28 or 29,
a CDR-H1 of SEQ ID NO: 52 or 53,
a CDR-H2 of SEQ ID NO: 64 or 65, and
a CDR-H3 of SEQ ID NO: 81 or 82;
(iii) a binding agent comprising
a CDR-L1 of SEQ ID NO: 5 or 6,
a CDR-L2 of SEQ ID NO: 20 or 21,
a CDR-L3 of SEQ ID NO: 30 or 31,
a CDR-H1 of SEQ ID NO: 54 or 55,
a CDR-H2 of SEQ ID NO: 66 or 67, and
a CDR-H3 of SEQ ID NO: 83 or 84;
(iv) a binding agent comprising
a CDR-L1 of SEQ ID NO: 7 or 8,
a CDR-L2 of SEQ ID NO: 22 or 23,
a CDR-L3 of SEQ ID NO: 34 or 35,
a CDR-H1 of SEQ ID NO: 56 or 57,
a CDR-H2 of SEQ ID NO: 68 or 69, and
a CDR-H3 of SEQ ID NO: 85 or 86;
(v) a binding agent comprising
a CDR-L1 of SEQ ID NO: 9 or 10,
a CDR-L2 of SEQ ID NO: 24 or 25,
a CDR-L3 of SEQ ID NO: 34 or 35
a CDR-H1 of SEQ ID NO: 58 or 59
a CDR-H2 of SEQ ID NO: 70 or 71, and
a CDR-H3 of SEQ ID NO: 87 or 88;
(vi) a binding agent comprising
a CDR-L1 of SEQ ID NO: 11 or 12,
a CDR-L2 of SEQ ID NO: 24 or 25,
a CDR-L3 of SEQ ID NO: 34 or 35,
a CDR-H1 of SEQ ID NO: 58 or 59,
a CDR-H2 of SEQ ID NO: 74 or 75, and
a CDR-H3 of SEQ ID NO: 90 or 91; and
(vii) a binding agent comprising
a CDR-L1 of SEQ ID NO: 11 or 12,
a CDR-L2 of SEQ ID NO: 24 or 25,
a CDR-L3 of SEQ ID NO: 34 or 35,
a CDR-H1 of SEQ ID NO: 58 or 59
a CDR-H2 of SEQ ID NO: 72 or 73, and
a CDR-H3 of SEQ ID NO: 88 or 89.

### Claim 4 (depends on 3)

The binding agent of claim 3, wherein
the CDR-L1 is SEQ ID NO: 9 or 10,
the CDR-L2 is SEQ ID NO: 24 or 25,
the CDR-L3 is SEQ ID NO: 34 or 35,
the CDR-H1 is SEQ ID NO: 58 or 59,
the CDR-H2 is SEQ ID NO: 70 or 71, and
the CDR-H3 is SEQ ID NO: 87 or 88.

### Claim 5 (depends on 2)

The binding agent of claim 2, wherein the binding agent comprises a light chain having a sequence selected from SEQ ID NOs: 46-49.

### Claim 6 (depends on 2)

The binding agent of claim 2, wherein the binding agent comprises a heavy chain having a sequence selected from SEQ ID NOs: 105-108.

### Claim 7 (depends on 2)

The binding agent of claim 2, wherein the binding agent has a light chain having a sequence selected from SEQ ID NOs: 46-49 which comprises zero to five amino acid modifications selected from an amino acid addition, an amino acid deletion and an amino acid substitution the and a heavy chain having a sequence selected from SEQ ID NOs: 105-108 which comprises ene zero to five amino acid modifications selected from an amino acid addition, an amino acid deletion and an amino acid substitution.

### Claim 8 (depends on 7)

The binding agent of claim 7, wherein the binding agent has a light chain having a sequence comprising SEQ ID NO: 47 and a heavy chain having a sequence comprising SEQ ID NO: 108.

### Claim 9 (depends on 7)

The binding agent of claim 7, wherein the binding agent has a light chain having a sequence comprising SEQ ID NO: 47 and a heavy chain having a sequence comprising SEQ ID NO: 106.

### Claim 10 (depends on 7)

The binding agent of claim 7, wherein the binding agent has a light chain having a sequence comprising SEQ ID NO: 47 and a heavy chain having a sequence comprising SEQ ID NO: 105.

### Claim 11 (depends on 1)

The binding agent of claim 1, wherein the binding agent induces internalization of cMET on a human cancer cell.

### Claim 12 (depends on 1)

The binding agent of claim 1, wherein the binding agent induces degradation of cMET on a human cancer cell.

### Claim 13 (depends on 1)

The binding agent of claim 1, wherein the binding agent comprises an anti-neoplastic agent.

### Claim 14 (depends on 3)

A composition comprising a first binding agent that is the binding agent of claim 3, and a second binding agent that does not bind specifically to cMET.

### Claim 15 (depends on 14)

The composition of claim 14, wherein the first binding agent is the binding agent that specifically binds to the extracellular domain of cMET and the second binding agent is conjugated to the first binding agent.

### Claim 16 (depends on 1)

A pharmaceutical composition comprising the binding agent of claim 1, and a pharmaceutically acceptable excipient, diluent, additive or carrier.

### Claim 17 (depends on 1)

A method of treating a subject having or suspected of having a neoplastic disorder or cancer comprising:
a) providing a subject having, or suspected of having, a neoplastic disorder or cancer; and
b) administering a therapeutically effective amount of the binding agent of claim 1 to the subject.

### Claim 18 (depends on 17)

The method of claim 17, wherein the binding agent specifically binds to the extracellular domain of cMET expressed on one or more cells of the subject.

### Claim 19 (depends on 18)

The method of claim 18, wherein the binding agent inhibits mitosis of, and/or induces death of the one or more cells expressing cMET.

### Claim 20 (depends on 17)

The method of claim 17, wherein the neoplastic disorder or cancer is selected from the group consisting of lung carcinoma, breast carcinoma, ovarian carcinoma, kidney carcinoma, colorectal carcinoma, gastric carcinoma, thyroid carcinoma, pancreas carcinoma, neuroblastoma, or a squamous cell carcinoma of the head and neck, cervical cancer, hepatocellular cancer, sarcomas, mesothelioma, glioblastoma, multiple myeloma, melanoma, prostate and esophageal carcinoma.