# US 8,785,392 B2 · Method for inhibiting cancer metastasis by administration of the extracellular domain DLK1 or a DLK1-FC fusion protein

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- Number: US 8,785,392 B2
- Document ID: US8785392B2
- Status: Granted
- Kind: B2
- Application number: 13/142,818
- Filed: 2010-04-13
- Published: 2013-08-08
- Granted: 2014-07-22
- Earliest claimed: 2010-03-16
- Assignees: Korea Research Institute of Bioscience and Biotechnology
- Applicants: Young Woo Park; Kiwon Jo; Donghee Lee; Jung Yu; Ji Hyun Park; Chan-Woong Park; Eun Jin Kim; Yun Jung Park
- Inventors: Young Woo Park; Kiwon Jo; Donghee Lee; Jung Yu; Ji Hyun Park; Chan-Woong Park; Eun Jin Kim; Yun Jung Park
- Web page: https://patentgrep.com/patent/US8785392B2

## CPC

- C07K 16/00: Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- C07K 14/435: from animals; from humans
- C07K 14/475: Growth factors; Growth regulators
- C07K 2319/30: Non-immunoglobulin-derived peptide or protein having an immunoglobulin constant or Fc region, or a fragment thereof, attached thereto
- Y10S 424/809: involving immunoglobulin or antibody fragment, e.g. fab', fv, fc, heavy chain or light chain
- Y10S 530/866: involving immunoglobulin or antibody fragment, e.g. fab', fab, fv, fc, heavy chain or light chain
- 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
- Y10S: TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS

## Abstract

A recombinant expression vector, comprising extracellular soluble domain genes of DLK1 and IgG antibody Fc domain genes, is constructed, and DLK1-Fc fusion protein is expressed and purified at 293E cell. The invention confirmed the efficacy as a drug for inhibiting cancer metastasis by confirming markedly reduced migration of cancer cells by DLK1-Fc fusion protein and also computing pharmacokinetic parameters. DLK1-Fc fusion protein has relatively higher stability than non-fusion protein, significantly reduces migration of various cancer cell lines, and provides superior cancer metastasis inhibition effect even at small concentration. Accordingly, DLK1-Fc fusion protein can be used efficaciously as an effective ingredient of a composition for inhibiting cancer metastasis.

## Claims

### Claim 1

A method for inhibiting cancer metastasis, comprising: administering a pharmaceutically effective amount of the extracellular soluble domain of delta-like 1 homolog (DLK1) or a DLK1-Fc fusion protein comprising the extracellular soluble domain of DLK1 and a human antibody Fc domain to a subject with a metastatic cancer, wherein the extracellular soluble domain of DLK1 consists of the amino acid sequence of SEQ ID NO:4.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the cancer is selected from the group consisting of skin cancer, breast cancer, uterine cancer, colon cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, pancreatic cancer and stomach cancer.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the DLK1-Fc fusion protein is prepared by a method comprising:
i) preparing a recombinant vector containing a polynucleotide coding the DLK1-Fc fusion protein comprising the extracellular soluble domain of DLK1 consisting of the amino acid sequence of SEQ ID NO:4 and a human antibody Fc domain;
ii) preparing a recombinant cell line in which the recombinant vector is transfected into a host cell;
iii) culturing the recombinant cell line; and
iv) separating the DLK1-Fc fusion protein from the recombinant cell line culture.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the extracellular soluble domain of delta-like 1 homolog (DLK1) or a DLK1-Fc fusion protein comprising the extracellular soluble domain of DLK1 and a human antibody Fc domain inhibits the migration of cancer cells.

### Claim 5 (depends on 4)

The method according to claim 4, wherein the cancer cell is selected from the group consisting of skin cancer cell, breast cancer cell, uterine cancer cell, colon cancer cell, kidney cancer cell, liver cancer cell, lung cancer cell, ovarian cancer cell, pancreatic cancer cell and stomach cancer cell.