Mini-gastrin analogue, in particular for use in cck2 receptor positive tumour diagnosis and/or treatment

Patent metadata

Field	Value
Publication number	US-2016256580-A1
Application number	US-201415034943-A
Country	US
Kind code	A1
Filing date	Oct 23, 2014
Priority date	Nov 6, 2013
Publication date	Sep 8, 2016
Grant date	—

Abstract

A gastrin analogue shows high uptake in CCK-2 receptor positive tumors and simultaneously a very low accumulation in the kidneys. This is achieved by a mini-gastrin analogue PP-F11 having the formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH 2 , wherein Y is an amino acid replacing methionine and X is a chemical group attached to the peptide for diagnostic and/or therapeutic intervention at CCK-2 receptor relevant diseases. Very suitable compounds with respect to a high tumor to kidney ratio are mini-gastrin analogues with six D-glutamic acids or six glutamines. These compounds still possess a methionine which can be oxidized easily which is a disadvantage for clinical application under GMP due to the forms which may occur. The elimination of the methionine leads to a lower affinity to oxidation which in general favors the tumor-kidney-ratio. Ideally, the methionine is replaced by norleucine. This PP-F11N mini gastrin exhibits currently the best tumor-kidney-ratio and is the most promising candidate.

First claim

1 - 9 . (canceled)

10 . A mini-gastrin analogue PP-F11, comprising:
a formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH 2 , wherein Y stands for an amino acid replacing methionin and X stands for a chemical group attached to a peptide for at least one of a diagnostic intervention or a therapeutic intervention at CCK-2 receptor relevant diseases.

11 . The mini gastrin analogue PP-F11 according to claim 10 , wherein the methionin is replaced by a norleucin.

12 . The mini gastrin analogue PP-F11 according to claim 10 , wherein the X stands for a radio nuclide.

13 . The mini gastrin analogue PP-F11 according to claim 10 , wherein the X stands for an optically active chemical compound.

14 . The mini gastrin analogue PP-F11 according to claim 10 , wherein the X stands for a chemotherapeutic active compound.

15 . The mini gastrin analogue PP-F11 according to claim 10 , wherein the X stands for a nanoparticle or a liposome which have a diagnostic function or which have a therapeutic function by themselves or are loaded with an active compound.

16 . The mini gastrin analogue PP-F11 according to claim 12 , wherein said radio nuclide is selected from the group consisting of 177 Lu, 90 Y and 111 In.

17 . The mini gastrin analogue PP-F11 according to claim 15 , wherein said nanoparticle or said liposome are an optical active or MRI contrast agent.

18 . A method of performing an intervention, which comprises the step of:
providing a mini-gastrin analogue PP-F11 having a formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH2, wherein Y stands for an amino acid replacing methionin and X stands for a chemical group attached to a peptide for a diagnostic intervention at CCK-2 receptor relevant diseases.

19 . A method of performing an intervention, which comprises the step of:
providing a mini-gastrin analogue PP-F11 having a formula: PP-F11-X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH 2 , wherein Y stands for an amino acid replacing methionin and X stands for a chemical group attached to a peptide for a therapeutic intervention at CCK-2 receptor relevant diseases.

20 . The method according to claim 19 , which further comprises the step of replacing the methionine by a methionine isosteric amino acid with no oxidation potential and showing a high tumor affinity.

Assignees

• Scherrer Inst Paul

Inventors

• Behe Martin
• Schibli Roger

Classifications

• A61K51/08

  Peptides, e.g. proteins {, carriers being peptides, polyamino acids, proteins} · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P13/12

  of the kidneys · CPC title