# US 2016/0053018 A1 · Anti-human trop-2 antibody having anti-tumor activity in vivo

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- Number: US 2016/0053018 A1
- Document ID: US20160053018A1
- Status: Published application
- Kind: A1
- Application number: 14/729,953
- Filed: 2015-06-03
- Published: 2016-02-25
- Earliest claimed: 2010-05-17
- Assignees: Livtech, Inc.
- Applicants: Livtech, Inc.
- Inventors: Koji NAKAMURA; Kentaro OKAMURA; Maki TAMURA; Hiroyuki YANAI; Toru KANKE
- Web page: https://patentgrep.com/patent/US20160053018A1

## CPC

- C07K 16/303: {Liver or Pancreas}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6859: {the tumour determinant being from liver or pancreas cancer cell}
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- C07K 16/18: against material from animals or humans
- C07K 16/30: from tumour cells
- G01N 33/57515: of the breast
- G01N 33/57525: of the liver or pancreas
- G01N 33/57535: of the large intestine, e.g. colon, rectum or anus
- G01N 33/57555: of the prostate
- A61K 2039/505: {comprising antibodies}
- C07K 2317/33: Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
- C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- 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
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

The present invention provides: an antibody, which specifically reacts with hTROP-2 and has anti-tumor activity in vivo; a hybridoma, which produces the aforementioned antibody; a complex of the aforementioned antibody and a drug; a pharmaceutical composition for diagnosing or treating a tumor; a method for detecting a tumor; and a kit for detecting or diagnosing a tumor.

## Claims

### Claim 1

An antibody against human TROP-2, which has anti-tumor activity in vivo, wherein the amino acid sequences of CDR 1 to 3 of the H chain V region of the antibody are shown in SEQ ID NOS: 36 to 38, respectively, and/or the amino acid sequences of CDR 1 to 3 of the L chain V region of the antibody are shown in SEQ ID NOS: 41 to 43, respectively.

### Claim 2 (depends on 1)

The antibody according to claim 1, which exhibits 50% or more of tumor growth inhibitory activity at a dosage of 5 to 20 mg/kg body weight.

### Claim 3 (depends on 2)

The antibody according to claim 2, wherein the frequency of administration for exhibiting the tumor growth inhibitory activity is at most once a week.

### Claim 4 (depends on 1)

The antibody according to claim 1, which exhibits 50% or more of the tumor growth inhibitory activity by a single administration of the antibody at a dosage of 10 mg/kg body weight.

### Claim 5 (depends on 1)

The antibody according to claim 1, which has anti-tumor activity on two or more types of human tumor cell lines.

### Claim 6 (depends on 1)

The antibody according to claim 1, wherein the dissociation constant (Kd value) is 1.0×10−10 M or less.

### Claim 7 (depends on 1)

The antibody according to claim 1, which is a monoclonal antibody.

### Claim 8 (depends on 1)

The antibody according to claim 1, wherein the tumor is at least one type selected from the group consisting of human pancreatic cancer, human prostate cancer, human colon cancer and human breast cancer.

### Claim 9 (depends on 1)

The antibody according to claim 1, wherein the tumor is human pancreatic cancer.

### Claim 10 (depends on 1)

The antibody according to claim 1, wherein the tumor is a recurrent cancer or a metastatic cancer.

### Claim 11 (depends on 5)

The antibody according to claim 5, wherein the tumor cell lines are at least two types selected from the group consisting of a human pancreatic cancer cell line PK-59, a human pancreatic cancer cell line BxPC-3, a human pancreatic cancer cell line KP-3L, a human pancreatic cancer cell line KP-2, a human pancreatic cancer cell line PK-1, a human pancreatic cancer cell line PK-45H, a human pancreatic cancer cell line PK-45P, a human pancreatic cancer cell line TCC-PAN2, a human pancreatic cancer cell line SUIT-2, a human colon cancer cell line CACO-2, a human colon cancer cell line SW480, a human colon cancer cell line DLD-1, a human colon cancer cell line HCT 116, a human breast cancer cell line JIMT-1, a human breast cancer cell line HCC1143, a human breast cancer cell line MCF-7, a human prostate cancer cell line DU145 and a human prostate cancer cell line PC-3.

### Claim 12 (depends on 5)

The antibody according to claim 5, wherein the tumor cell lines are the human pancreatic cancer cell line PK-59 and the human pancreatic cancer cell line BxPC-3.

### Claim 13 (depends on 1)

The antibody according to claim 1, wherein the antibody is a genetically recombinant antibody.

### Claim 14 (depends on 13)

The antibody according to claim 13, wherein the genetically recombinant antibody is a chimeric antibody, a humanized antibody, or a human antibody.

### Claim 15

A genetically recombinant antibody against human TROP-2, which is a chimeric antibody, a humanized antibody, or a human antibody, and has anti-tumor activity in vivo, wherein the H chain V region of the chimeric antibody consists of the amino acid sequence shown in SEQ ID NO: 35 or the amino acid sequence consisting of amino acids at positions 20 to 134 in the amino acid sequence as shown in SEQ ID NO: 35, and/or the L chain V region thereof consists of the amino acid sequence shown in SEQ ID NO: 40 or the amino acid sequence consisting of amino acids at positions 21 to 127 in the amino acid sequence as shown in SEQ ID NO: 40.

### Claim 16

A monoclonal antibody against human TROP-2, which is produced by a hybridoma having accession No. FERM BP-11251.

### Claim 17 (depends on 1)

An antigen binding fragment derived from the antibody according to claim 1.

### Claim 18

An antigen binding fragment derived from an antibody against human TROP-2, which has anti-tumor activity in vivo, wherein the fragment comprises the amino acid sequences shown in SEQ ID NOS: 36 to 38 and/or the amino acid sequences shown in SEQ ID NOS: 41 to 43.

### Claim 19 (depends on 18)

The antigen binding fragment according to claim 18, which comprises the amino acid sequence shown in SEQ ID NO: 35 or the amino acid sequence consisting of amino acids at positions 20 to 134 in the amino acid sequence as shown in SEQ ID NO: 35 and/or the amino acid sequence shown in SEQ ID NO: 40 or the amino acid sequence consisting of amino acids at positions 21 to 127 in the amino acid sequence as shown in SEQ ID NO: 40.

### Claim 20

A hybridoma producing a monoclonal antibody against human TROP-2, which has accession No. FERM BP-11251.

### Claim 21 (depends on 1)

An antibody-drug conjugate, which comprises the antibody according to claim 1 and a substance having anti-tumor activity and/or cell-killing activity.

### Claim 22 (depends on 17)

An antibody fragment-drug conjugate, which comprises the antibody fragment according to claim 17 and a substance having anti-tumor activity and/or cell-killing activity.

### Claim 23 (depends on 21)

The conjugate according to claim 21, wherein the tumor is at least one type selected from the group consisting of human pancreatic cancer, human prostate cancer, human colon cancer and human breast cancer.

### Claim 24 (depends on 21)

The conjugate according to claim 21, wherein the tumor is a recurrent cancer of a metastatic cancer.

### Claim 25 (depends on 22)

The conjugate according to claim 22, wherein the tumor is at least one type selected from the group consisting of human pancreatic cancer, human prostate cancer, human colon cancer and human breast cancer.

### Claim 26 (depends on 22)

The conjugate according to claim 22, wherein the tumor is a recurrent cancer of a metastatic cancer.