# US 11,111,311 B2 · Anti-DLL3 antibody

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- Number: US 11,111,311 B2
- Document ID: US11111311B2
- Status: Granted
- Kind: B2
- Application number: 14/846,135
- Filed: 2015-09-04
- Published: 2015-12-24
- Granted: 2021-09-07
- Earliest claimed: 2010-01-29
- Assignees: Chugai Seiyaku Kabushiki Kaisha; The University of Tokyo
- Applicants: Chugai Seiyaku Kabushiki Kaisha; The University of Tokyo
- Inventors: Kenji Yoshida; Hiroyuki Aburatani; Shumpei Ishikawa
- Web page: https://patentgrep.com/patent/US11111311B2

## CPC

- C07K 16/3023: {Lung}
- A61K 39/395: Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61P 35/00: Antineoplastic agents
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C12Q 1/6886: for cancer (immunoassay for cancer G01N33/575)
- G01N 33/575: for cancer
- A61K 2039/505: {comprising antibodies}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/30: characterized by aspects of specificity or valency
- C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC]
- C07K 2317/77: Internalization into the cell
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- C12Q 2600/118: Prognosis of disease development
- G01N 2333/4703: Regulators; Modulating activity
- 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
- C12Q: MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS (immunoassay G01N33/53); COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- 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

It is intended to disclose an antibody which binds to DLL3 protein. Preferably, the antibody of the present invention recognizes a region from amino acids 216 to 492 in human DLL3 having the amino acid sequence as set forth in SEQ ID NO: 1. The present invention also provides a pharmaceutical composition, for example, an anticancer agent, comprising the antibody of the present invention as an active ingredient. The present invention further discloses a method for diagnosing cancer using the antibody of the present invention and a diagnostic drug for cancer comprising the antibody of the present invention.

## Claims

### Claim 1

An antibody that binds to DLL3 having the amino acid sequence of SEQ ID NO: 1, wherein said antibody binds to a region between amino acids 216 to 492 of SEQ ID NO: 1, wherein the antibody has an internalizing activity and is either conjugated to, or is capable of being conjugated to, one or more cytotoxic substances,
and wherein the anti-DLL3 antibody is
an antibody comprising a heavy chain variable region comprising heavy chain CDR1 having the amino acid sequence as set forth in SEQ ID NO: 36, heavy chain CDR2 having the amino acid sequence as set forth in SEQ ID NO: 37, and heavy chain CDR3 having the amino acid sequence as set forth in SEQ ID NO: 38, and a light chain variable region comprising light chain CDR1 having the amino acid sequence as set forth in SEQ ID NO: 42, light chain CDR2 having the amino acid sequence as set forth in SEQ ID NO: 43, and light chain CDR3 having the amino acid sequence as set forth in SEQ ID NO: 44.

### Claim 2 (depends on 1)

The antibody according to claim 1, wherein the antibody is a chimeric or humanized antibody.

### Claim 3 (depends on 1)

The antibody according to claim 1, wherein the antibody is conjugated to one or more cytotoxic substances.

### Claim 4 (depends on 3)

A method of inducing death of a cell expressing DLL3 having the amino acid sequence set forth in SEQ ID NO: 1, comprising contacting the cell with the antibody of claim 3.

### Claim 5 (depends on 4)

The method according to claim 4, wherein the antibody is a chimeric or humanized antibody.

### Claim 6 (depends on 3)

A method of suppressing growth of a cell expressing DLL3 as set forth in SEQ ID NO: 1, comprising contacting the cell with the antibody of claim 3.

### Claim 7 (depends on 6)

The method according to claim 6, wherein the antibody is a chimeric or humanized antibody.

### Claim 8 (depends on 3)

A method of treating cancer, comprising administering the antibody of claim 3 to a subject in need of such treatment.

### Claim 9 (depends on 8)

The method according to claim 8, wherein the antibody is a chimeric or humanized antibody.

### Claim 10 (depends on 8)

The method according to claim 8, wherein the cancer is a lung cancer.

### Claim 11 (depends on 10)

The method according to claim 10, wherein the lung cancer is a small-cell lung cancer.

### Claim 12 (depends on 1)

A method of identifying or selecting an anti-DLL3 antibody having internalizing activity that can bind to a region between amino acids 216 to 492 of SEQ ID NO: 1,
wherein said method comprises identifying or selecting, from a plurality of antibodies, an antibody which binds to the same epitope in the DLL3 protein to which the antibody of claim 1 binds, or which competes with the antibody of claim 1 for binding to the DLL3 protein.

### Claim 13 (depends on 1)

A method of identifying or selecting an anti-DLL3 antibody having internalizing activity that can bind to a region between amino acids 216 to 492 of SEQ ID NO: 1,
wherein said method comprises identifying or selecting, from a plurality of antibodies, an antibody which binds to the same epitope in the DLL3 protein to which the antibody of claim 1 binds.

### Claim 14 (depends on 1)

A method of identifying or selecting an anti-DLL3 antibody having internalizing activity that can bind to a region between amino acids 216 to 492 of SEQ ID NO: 1,
wherein said method comprises identifying or selecting, from a plurality of antibodies, an antibody which competes with the antibody of claim 1 for binding to the DLL3 protein.

### Claim 15

A method of identifying or selecting an anti-DLL3 antibody having internalizing activity that can bind to a region between amino acids 216 to 492 of SEQ ID NO: 1,
wherein said method comprises identifying or selecting, from a plurality of antibodies, an antibody which binds to a region between amino acids 216 to 492 of SEQ ID NO: 1.

### Claim 16 (depends on 15)

The method according to claim 15, wherein the antibody that is identified or selected binds to the same epitope in the DLL3 protein as an antibody comprising a heavy chain variable region comprising heavy chain CDR1 having the amino acid sequence as set forth in SEQ ID NO: 36, heavy chain CDR2 having the amino acid sequence as set forth in SEQ ID NO: 37, and heavy chain CDR3 having the amino acid sequence as set forth in SEQ ID NO: 38, and a light chain variable region comprising light chain CDR1 having the amino acid sequence as set forth in SEQ ID NO: 42, light chain CDR2 having the amino acid sequence as set forth in SEQ ID NO: 43, and light chain CDR3 having the amino acid sequence as set forth in SEQ ID NO: 44.

### Claim 17 (depends on 15)

The method according to claim 15, wherein the antibody that is identified or selected competes for binding to the DLL3 protein with an antibody comprising a heavy chain variable region comprising heavy chain CDR1 having the amino acid sequence as set forth in SEQ ID NO: 36, heavy chain CDR2 having the amino acid sequence as set forth in SEQ ID NO: 37, and heavy chain CDR3 having the amino acid sequence as set forth in SEQ ID NO: 38, and a light chain variable region comprising light chain CDR1 having the amino acid sequence as set forth in SEQ ID NO: 42, light chain CDR2 having the amino acid sequence as set forth in SEQ ID NO: 43, and light chain CDR3 having the amino acid sequence as set forth in SEQ ID NO: 44.
