# US 7,608,242 B2 · Peptide-chelate conjugates

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 7,608,242 B2
- Document ID: US7608242B2
- Status: Granted
- Kind: B2
- Application number: 10/469,801
- Filed: 2002-03-01
- Published: 2006-10-05
- Granted: 2009-10-27
- Earliest claimed: 2001-03-02
- Assignees: Ge Healthcare Limited
- Inventors: Alan Cuthbertson; Marivi Mendizabal; Mark Dixon; Anthony E. Storey; Edward R. Bacon; Vinay Chandrakant Desai; Sudhakar Kasina; Henry Raphael Wolfe
- Web page: https://patentgrep.com/patent/US7608242B2

## CPC

- C07K 7/06: having 5 to 11 amino acids
- A61K 51/088: {conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10)}
- C07K 14/245: Escherichia (G)
- G01N 33/57535: of the large intestine, e.g. colon, rectum or anus
- 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)
- 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

A peptide-chelate conjugate with affinity for the ST receptor is disclosed, wherein the chelate is tetradentate. The peptide-chelate conjugate of the invention may be labelled with a radiometal to provide a metal complex. A radiopharmaceutical composition comprising the metal complex is provided. which is suitable for the diagnostic imaging of colorectal cancer. Also provided for in the invention is a kit for the preparation of the radiopharmaceutical preparation.

## Claims

### Claim 1

A peptide-chelate conjugate comprising a peptide of SEQ ID Nos. 1 to 7 having affinity for the ST receptor conjugated to a tetradentate chelating agent, where the tetradentate chelating agent is chosen from diaminedioximes and N3S ligands.

### Claim 2 (depends on 1)

The peptide-chelate conjugate of claim 1 wherein the tetradentate chelating agent is of formula A:
Wherein RA1-RA6 are all CH3 and Q is —(CH2)2NR(CH2)2— and wherein R is H or C1-10 alkyl, alkylaryl, alkoxyalkyl, hydroxyalkyl, fluoroalkyl, aminoalkyl, or carboxyalkyl.

### Claim 3 (depends on 1)

The peptide-chelate conjugate of claim 1 where the tetradentate chelating agent is of formula B:
where RB1 and RB2 are both H and X is a thiol protecting group.

### Claim 4 (depends on 1)

The peptide-chelate conjugate of claim 1 where the conjugation is either at the N-terminus or at the C-terminus of the peptide.

### Claim 5 (depends on 1)

The peptide-chelate conjugate of claim 1 which further comprises a linker group between the peptide and the tetradentate chelating agent.

### Claim 6 (depends on 5)

The peptide-chelate conjugate of claim 5 where the linker group comprises a peptide sequence of 5 to 9 amino acids.

### Claim 7 (depends on 5)

The peptide-chelate conjugate of claim 5 where the linker group is selected from -poly-Lys-, -poly-Glu-, -(Gly)2-Glu-(Lys)3-, (Gly)2-Glu-Lys-Glu-Lys-, (Phe)2-(CH2)5—, (Lys)6-Gly-, -(Gly)3-(DGlu)3- and -(Gly)3-(aminocaproic acid)2-.

### Claim 8 (depends on 1)

A metal complex which comprises a radiometal complexed to the tetradentate chelating agent of the peptide-chelate conjugate of claim 1.

### Claim 9 (depends on 8)

The metal complex of claim 8 where the radiometal is chosen from 64Cu, 65Cu and 99mTc.

### Claim 10 (depends on 8)

The metal complex of claim 8 where the radiometal is 99mTc.

### Claim 11 (depends on 8)

A radiopharmaceutical composition in a form suitable for human administration, which comprises the metal complex of claim 8.

### Claim 12 (depends on 11)

The radiopharmaceutical composition of claim 11, where the radiometal is 99mTc.

### Claim 13 (depends on 1, 11)

A kit for the preparation of the radiopharmaceutical composition of claim 11 which comprises a vial containing:
i) the peptide-chelate conjugate of claim 1; and,
ii) a pharmaceutically acceptable reducing agent.

### Claim 14 (depends on 13)

The kit of claim 13 where the reducing agent is a stannous salt.

### Claim 15 (depends on 13)

The kit of claim 13 further comprising one or more of stabilisers; antioxidants; bulking agents for lyophilisation; and solubilisers.