# US 8,541,543 B2 · Peptides specific for hepatocellular carcinoma cells and applications thereof

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- Number: US 8,541,543 B2
- Document ID: US8541543B2
- Status: Granted
- Kind: B2
- Application number: 12/292,401
- Filed: 2008-11-18
- Published: 2009-05-28
- Granted: 2013-09-24
- Earliest claimed: 2007-11-20
- Assignees: Academia Sinica
- Applicants: Han-Chung Wu; Chin-Tarng Lin; Albert Lo
- Inventors: Han-Chung Wu; Chin-Tarng Lin; Albert Lo
- Web page: https://patentgrep.com/patent/US8541543B2

## CPC

- G01N 33/57525: of the liver or pancreas
- A61P 35/00: Antineoplastic agents
- C07K 7/08: having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68)
- A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide. Novel treatment strategies derived from increased knowledge of molecular oncology are constantly being developed to cure this disease. Here, we used phage display to identify novel peptides, including (SP94), which binds specifically to HCC cells. In vitro, the phage clone PC94 binds to HCC cell lines. In vivo, PC94 homed specifically to tumor tissues but not to normal visceral organs in SCID mice bearing human HCC xenografts. The homing ability could be competitively inhibited by synthetic peptide, SP94. PC94 localized to tumor tissues but could not be detected in SP94-competed tumor tissues or in normal organs. In addition, PC94 recognized the tumor tissue but not non-tumor tissue in surgical specimens from HCC patients, with a positive rate of 61.3% (19/31). With the conjugation of SP94 and liposomal doxorubicin, a targeted drug delivery system enhanced the therapeutic efficacy against HCC xenografts through enhanced tumor apoptosis and decreased tumor angiogenesis. Our results indicate that SP94 can improve the systemic treatment of patients with advanced HCC.

## Claims

### Claim 1

A purified, synthesized or isolated polypeptide consisting of a polypeptide at least 90% identical to the sequence of SEQ ID NO: 2, wherein the polypeptide comprises SEQ ID NO: 34.

### Claim 2 (depends on 1)

The polypeptide of claim 1, wherein the polypeptide is SEQ ID NO: 2.

### Claim 3 (depends on 1)

The polypeptide of claim 1, wherein the polypeptide is conjugated to doxorubicin.

### Claim 4 (depends on 2)

The polypeptide of claim 2, wherein the polypeptide is conjugated to doxorubicin.

### Claim 5 (depends on 1)

A fusion protein comprising a first polypeptide fused to a second polypeptide, wherein the first polypeptide is the polypeptide of claim 1.

### Claim 6 (depends on 2)

A fusion protein comprising a first polypeptide fused to a second polypeptide, wherein the first polypeptide is the polypeptide of claim 2.

### Claim 7 (depends on 1)

A liposome comprising at least one polypeptide of claim 1.

### Claim 8 (depends on 7)

The liposome of claim 7, wherein the polypeptide is SEQ ID NO: 2.

### Claim 9 (depends on 7)

The liposome of claim 7, wherein the liposome further comprises doxorubicin.
