# US 2014/0154243 A1 · Specific binding agents to hepatocyte growth factor

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- Number: US 2014/0154243 A1
- Document ID: US20140154243A1
- Status: Published application
- Kind: A1
- Application number: 14/086,864
- Filed: 2013-11-21
- Published: 2014-06-05
- Earliest claimed: 2003-07-18
- Assignees: Amgen Fremont Inc.; Amgen Inc.
- Applicants: Amgen Fremont Inc.; Amgen Inc.
- Inventors: Teresa L BURGESS; Angela COXON; Larry L GREEN; Ke ZHANG
- Web page: https://patentgrep.com/patent/US20140154243A1

## CPC

- C07K 16/22: against growth factors {; against growth regulators}
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- 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 2317/56: variable (Fv) region, i.e. VH and/or VL
- 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 2317/92: 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Specific binding agents that interact with hepatocyte growth factor (HGF) are described. Methods of treating cancer by administering a pharmaceutically effective amount of a specific binding agent to HGF are described. Methods of detecting the amount of HGF in a sample using a specific binding agent to HGF are described.

## Claims

### Claim 1

A method of treating cancer in a patient, the method comprising administering an antibody that binds human hepatocyte growth factor (HGF), wherein the antibody is selected from the group consisting of:
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:24 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 25 from residue 20 to residue 141;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:26 from residue 21 to residue 133 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 27 from residue 20 to residue 137;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:28 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 29 from residue 20 to residue 139;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:30 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 31 from residue 20 to residue 148;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:32 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 33 from residue 20 to residue 139;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:34 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 35 from residue 20 to residue 144;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:36 from residue 21 to residue 133 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 37 from residue 20 to residue 142;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:38 from residue 21 to residue 128 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 39 from residue 20 to residue 139;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:40 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 41 from residue 20 to residue 140; and
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:42 from residue 21 to residue 128 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 43 from residue 20 to residue 139.

### Claim 2 (depends on 1)

The method of claim 1, wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 36 from residue 21 to residue 133 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 37 from residue 20 to residue 142.

### Claim 3 (depends on 1)

The method of claim 1, wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 38 from residue 21 to residue 128 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 39 from residue 20 to residue 139.

### Claim 4 (depends on 1)

The method of claim 1, wherein the antibody is an immunologically functional immunoglobulin fragment that binds human HGF.

### Claim 5 (depends on 1)

The method of claim 1, further comprising administering chemotherapy.

### Claim 6 (depends on 1)

The method of claim 1, further comprising administering radiation therapy.

### Claim 7

A method for treating cancer in a patient, the method comprising administering an antibody that binds human hepatocyte growth factor (HGF), wherein the antibody is selected from the group consisting of:
an antibody comprising a light chain comprising SEQ ID NOs: 60, 70, and 80, and a heavy chain comprising SEQ ID NOs: 90, 100 and 110;
an antibody comprising a light chain comprising SEQ ID NOs: 61, 71, and 81, and a heavy chain comprising SEQ ID NOs: 91, 101, and 111;
an antibody comprising a light chain comprising SEQ ID NOs: 62, 72, and 82, and a heavy chain comprising SEQ ID NOs: 92, 102, and 112;
an antibody comprising a light chain comprising SEQ ID NOs: 63, 73, and 83, and a heavy chain comprising SEQ ID NOs: 93, 103, and 113;
an antibody comprising a light chain comprising SEQ ID NOs: 64, 74, and 84, and a heavy chain comprising SEQ ID NOs: 94, 104, and 114;
an antibody comprising a light chain comprising SEQ ID NOs: 65, 75, and 85, and a heavy chain comprising SEQ ID NOs: 95, 105, and 115;
an antibody comprising a light chain comprising SEQ ID NOs: 66, 76, and 86, and a heavy chain comprising SEQ ID NOs: 96, 106, and 116;
an antibody comprising a light chain comprising SEQ ID NOs: 67, 77, and 87, and a heavy chain comprising SEQ ID NOs: 97, 107, and 117;
an antibody comprising a light chain comprising SEQ ID NOs: 68, 78, and 88, and a heavy chain comprising SEQ ID NOs: 98, 108, and 118; and
an antibody comprising a light chain comprising SEQ ID NOs: 69, 79, and 89, and a heavy chain comprising SEQ ID NOs: 99, 109, and 119.

### Claim 8 (depends on 7)

The method of claim 7, wherein the antibody comprises a light chain comprising SEQ ID NOs: 66, 76, and 86, and a heavy chain comprising SEQ ID NOs: 96, 106, and 116.

### Claim 9 (depends on 7)

The method of claim 7, wherein the antibody comprises a light chain comprising SEQ ID NOs: 67, 77, and 87, and a heavy chain comprising SEQ ID NOs: 97, 107, and 117.

### Claim 10 (depends on 7)

The method of claim 7, wherein the antibody is an immunologically functional immunoglobulin fragment that binds human HGF.

### Claim 11 (depends on 7)

The method of claim 7, further comprising administering chemotherapy.

### Claim 12 (depends on 7)

The method of claim 7, further comprising administering radiation therapy.

### Claim 13

A method for treating cancer in a patient, the method comprising administering a fully human antibody that binds human hepatocyte growth factor (HGF) comprising a light chain and a heavy chain, wherein the light chain comprises SEQ ID NOs: 67, 77, and 87 and the heavy chain comprises SEQ ID NOs: 97, 107, and 117.

### Claim 14 (depends on 13)

The method of claim 13, wherein the light chain further comprises the amino acid sequence of SEQ ID NO: 44 and the heavy chain further comprises the amino acid sequence of SEQ ID NO: 46.

### Claim 15 (depends on 13)

The method of claim 13, wherein the antibody is an immunologically functional immunoglobulin fragment that binds human HGF.

### Claim 16 (depends on 13)

The method of claim 13, further comprising administering chemotherapy.

### Claim 17 (depends on 13)

The method of claim 13, further comprising administering radiation therapy.

### Claim 18

A method for treating cancer in a patient, the method comprising administering a fully human antibody that binds human hepatocyte growth factor (HGF) comprising a light chain and a heavy chain, wherein the light chain comprises the amino acid sequence of SEQ ID NO: 38 from residue 21 to residue 128 and the heavy chain comprises the amino acid sequence of SEQ ID NO: 39 from residue 20 to residue 139.

### Claim 19 (depends on 18)

The method of claim 18, wherein the light chain further comprises the amino acid sequence of SEQ ID NO: 44 and the heavy chain further comprises the amino acid sequence of SEQ ID NO: 46.

### Claim 20 (depends on 18)

The method of claim 18, wherein the antibody is an immunologically functional immunoglobulin fragment that binds human HGF.

### Claim 21 (depends on 18)

The method of claim 18, further comprising administering chemotherapy.

### Claim 22 (depends on 18)

The method of claim 18, further comprising administering radiation therapy.

### Claim 23

A method of treating cancer in a cancer patient, the method comprising administering an antibody which is capable of binding at least one amino acid sequence consisting of SEQ ID NO: 164 or SEQ ID NO: 165, wherein the antibody is humanized or fully human.

### Claim 24 (depends on 23)

The method of claim 23, wherein the antibody is an immunologically functional immunoglobulin fragment that binds human HGF.

### Claim 25 (depends on 23)

The method of claim 23, further comprising administering chemotherapy.

### Claim 26 (depends on 23)

The method of claim 23, further comprising administering radiation therapy.

### Claim 27

A method of treating a solid tumor in a patient, the method comprising administering an antibody that binds human hepatocyte growth factor (HGF), wherein the antibody is selected from the group consisting of:
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:24 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 25 from residue 20 to residue 141;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:26 from residue 21 to residue 133 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 27 from residue 20 to residue 137;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:28 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 29 from residue 20 to residue 139;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:30 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 31 from residue 20 to residue 148;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:32 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 33 from residue 20 to residue 139;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:34 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 35 from residue 20 to residue 144;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:36 from residue 21 to residue 133 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 37 from residue 20 to residue 142;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:38 from residue 21 to residue 128 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 39 from residue 20 to residue 139;
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:40 from residue 23 to residue 129 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 41 from residue 20 to residue 140; and
an antibody comprising a light chain comprising the amino acid sequence of SEQ ID NO:42 from residue 21 to residue 128 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 43 from residue 20 to residue 139.

### Claim 28 (depends on 27)

The method of claim 27, wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 36 from residue 21 to residue 133 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 37 from residue 20 to residue 142.

### Claim 29 (depends on 27)

The method of claim 27, wherein the antibody comprises a light chain comprising the amino acid sequence of SEQ ID NO: 38 from residue 21 to residue 128 and a heavy chain comprising the amino acid sequence of SEQ ID NO: 39 from residue 20 to residue 139.

### Claim 30 (depends on 27)

The method of claim 27, wherein the antibody is an immunologically functional immunoglobulin fragment that binds human HGF.

### Claim 31 (depends on 27)

The method of claim 27, further comprising administering chemotherapy.

### Claim 32 (depends on 27)

The method of claim 27, further comprising administering radiation therapy.

### Claim 33

A method for treating a solid tumor in a patient, the method comprising administering an antibody that binds human hepatocyte growth factor (HGF), wherein the antibody is selected from the group consisting of:
an antibody comprising a light chain comprising SEQ ID NOs: 60, 70, and 80, and a heavy chain comprising SEQ ID NOs: 90, 100 and 110;
an antibody comprising a light chain comprising SEQ ID NOs: 61, 71, and 81, and a heavy chain comprising SEQ ID NOs: 91, 101, and 111;
an antibody comprising a light chain comprising SEQ ID NOs: 62, 72, and 82, and a heavy chain comprising SEQ ID NOs: 92, 102, and 112;
an antibody comprising a light chain comprising SEQ ID NOs: 63, 73, and 83, and a heavy chain comprising SEQ ID NOs: 93, 103, and 113;
an antibody comprising a light chain comprising SEQ ID NOs: 64, 74, and 84, and a heavy chain comprising SEQ ID NOs: 94, 104, and 114;
an antibody comprising a light chain comprising SEQ ID NOs: 65, 75, and 85, and a heavy chain comprising SEQ ID NOs: 95, 105, and 115;
an antibody comprising a light chain comprising SEQ ID NOs: 66, 76, and 86, and a heavy chain comprising SEQ ID NOs: 96, 106, and 116;
an antibody comprising a light chain comprising SEQ ID NOs: 67, 77, and 87, and a heavy chain comprising SEQ ID NOs: 97, 107, and 117;
an antibody comprising a light chain comprising SEQ ID NOs: 68, 78, and 88, and a heavy chain comprising SEQ ID NOs: 98, 108, and 118; and
an antibody comprising a light chain comprising SEQ ID NOs: 69, 79, and 89, and a heavy chain comprising SEQ ID NOs: 99, 109, and 119.

### Claim 34 (depends on 33)

The method of claim 33, wherein the antibody comprises a light chain comprising SEQ ID NOs: 66, 76, and 86, and a heavy chain comprising SEQ ID NOs: 96, 106, and 116.

### Claim 35 (depends on 33)

The method of claim 33, wherein the antibody comprises a light chain comprising SEQ ID NOs: 67, 77, and 87, and a heavy chain comprising SEQ ID NOs: 97, 107, and 117.

### Claim 36 (depends on 33)

The method of claim 33, wherein the antibody is an immunologically functional immunoglobulin fragment that binds human HGF.

### Claim 37 (depends on 33)

The method of claim 33, further comprising administering chemotherapy.

### Claim 38 (depends on 33)

The method of claim 33, further comprising administering radiation therapy.

### Claim 39

A method for treating a solid tumor in a patient, the method comprising administering a fully human antibody that binds human hepatocyte growth factor (HGF) comprising a light chain and a heavy chain, wherein the light chain comprises SEQ ID NOs: 67, 77, and 87 and the heavy chain comprises SEQ ID NOs: 97, 107, and 117.

### Claim 40 (depends on 39)

The method of claim 39, wherein the light chain further comprises the amino acid sequence of SEQ ID NO: 44 and the heavy chain further comprises the amino acid sequence of SEQ ID NO: 46.

### Claim 41 (depends on 39)

The method of claim 39, wherein the antibody is an immunologically functional immunoglobulin fragment that binds human HGF.

### Claim 42 (depends on 39)

The method of claim 39, further comprising administering chemotherapy.

### Claim 43 (depends on 39)

The method of claim 39, further comprising administering radiation therapy.

### Claim 44

A method for treating a solid tumor in a patient, the method comprising administering a fully human antibody that binds human hepatocyte growth factor (HGF) comprising a light chain and a heavy chain, wherein the light chain comprises the amino acid sequence of SEQ ID NO: 38 from residue 21 to residue 128 and the heavy chain comprises the amino acid sequence of SEQ ID NO: 39 from residue 20 to residue 139.

### Claim 45 (depends on 44)

The method of claim 44, wherein the light chain further comprises the amino acid sequence of SEQ ID NO: 44 and the heavy chain further comprises the amino acid sequence of SEQ ID NO: 46.

### Claim 46 (depends on 44)

The method of claim 44, wherein the antibody is an immunologically functional immunoglobulin fragment that binds human HGF.

### Claim 47 (depends on 44)

The method of claim 44, further comprising administering chemotherapy.

### Claim 48 (depends on 44)

The method of claim 44, further comprising administering radiation therapy.

### Claim 49

A method of treating cancer in a cancer patient, the method comprising administering an antibody which is capable of binding at least one amino acid sequence consisting of SEQ ID NO: 164 or SEQ ID NO: 165, wherein the antibody is humanized or fully human.

### Claim 50 (depends on 49)

The method of claim 49, wherein the antibody is an immunologically functional immunoglobulin fragment that binds human hepatocyte growth factor.

### Claim 51 (depends on 49)

The method of claim 49, further comprising administering chemotherapy.

### Claim 52 (depends on 49)

The method of claim 49, further comprising administering radiation therapy.