# US 7,745,571 B2 · Peptide inhibitors of IASPP

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- Number: US 7,745,571 B2
- Document ID: US7745571B2
- Status: Granted
- Kind: B2
- Application number: 12/043,058
- Filed: 2008-03-05
- Published: 2008-10-23
- Granted: 2010-06-29
- Earliest claimed: 2002-10-07
- Assignees: Ludwig Institute for Cancer Research; Genome Research Limited; Ucl Cruciform Limited
- Inventors: Xin Lu; Patricia Kuwabara; David Selwood
- Web page: https://patentgrep.com/patent/US7745571B2

## CPC

- A61K 38/1709: {from mammals}
- A61K 38/193: {Colony stimulating factors [CSF]}
- A61K 38/50: acting on carbon-nitrogen bonds, other than peptide bonds (3.5), e.g. asparaginase
- A61P 35/00: Antineoplastic agents
- C07K 14/4747: {Apoptosis related proteins}
- 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
- 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)

## Abstract

The invention relates to a polypeptide or part thereof which inhibits the apoptotic activity of the tumor suppressor protein p53, and includes screening methods to identify agents which interfere with the activity of the polypeptide.

## Claims

### Claim 1

An isolated peptide consisting of an amino acid sequence selected from the group consisting of: DGPEETD (SEQ ID NO: 2); GPEETD (SEQ ID NO: 1); TTLSDG (SEQ ID NO: 3); AEFGDE (SEQ ID NO: 8, amino acids 294-299); or PRNYFG (SEQ ID NO: 4).

### Claim 2

An isolated peptide that is 6-20 amino acids in length and that comprises the sequence AEFGDE (SEQ ID NO: 8, positions 294-299), wherein the isolated peptide is capable of inhibiting iASPP binding to p53.

### Claim 3

An isolated peptide consisting of:
(a) an amino acid sequence selected from the group consisting of: DGPEETD (SEQ ID NO: 2); GPEETD (SEQ ID NO: 1); TTLSDG (SEQ ID NO: 3); AEFGDE (SEQ ID NO: 8, amino acids 294-299); or PRNYFG (SEQ ID NO: 4); and (b) an arginine tag.

### Claim 4 (depends on 1)

A composition comprising the peptide according to claim 1 and a carrier, diluent, or excipient.

### Claim 5 (depends on 1, 2)

A composition comprising at least one peptide according to claim 1 or claim 2 and at least one anti-cancer agent.

### Claim 6 (depends on 5)

The composition according to claim 5 wherein said anticancer agent is selected from the group consisting of: cisplatin; carboplatin; cyclosphosphamide; melphalan; carmusline; methotrexate; 5-fluorouracil; cytarabine; mercaptopurine; daunorubicin; doxorubicin; epirubicin; vinblastine; vincristine; dactinomycin; mitomycin C; taxol; L-asparaginase; G-CSF; etoposide; colchicine; derferoxamine mesylate; and camptothecin.

### Claim 7 (depends on 6)

The composition according to claim 6 wherein said anticancer agent is cisplatin.

### Claim 8 (depends on 6)

The composition according to claim 6 wherein said anticancer agent is doxorubicin.

### Claim 9 (depends on 1, 2)

A complex comprising the peptide according to claim 1 or claim 2 and an antibody, or antigen-binding domain thereof.

### Claim 10 (depends on 9)

The complex according to claim 9 wherein said antibody or antigen binding domain is a cell-specific antibody.

### Claim 11 (depends on 9)

The complex according to claim 9 wherein said antibody is a cancer cell-specific antibody.

### Claim 12

An isolated peptide consisting of amino acids AEFGDE (SEQ ID NO: 8, amino acids 294-299) attached to an arginine tag.

### Claim 13 (depends on 12)

A composition comprising the peptide according to claim 12 and at least one anti-cancer agent.

### Claim 14 (depends on 12)

A complex comprising the peptide according to claim 12 and an antibody or antigen-binding domain thereof.

### Claim 15 (depends on 2)

The peptide of claim 2, wherein the peptide includes an arginine tag.

### Claim 16 (depends on 15)

The peptide of claim 15, wherein the arginine tag contains 2-10 residues.