Mini-gastrin analogue, in particular for use in CCK2 receptor positive tumour diagnosis and/or treatment

Patent metadata

Field	Value
Publication number	US-11623014-B2
Application number	US-202017127265-A
Country	US
Kind code	B2
Filing date	Dec 18, 2020
Priority date	Nov 6, 2013
Publication date	Apr 11, 2023
Grant date	Apr 11, 2023

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-NH2, 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

The invention claimed is:

1. A pharmaceutical composition comprising a therapeutically effective amount of a mini-gastrin analogue having the formula:
X-DGlu-DGlu-DGlu-DGlu-DGlu-DGlu-Ala-Tyr-Gly-Trp-Y-Asp-Phe-NH 2 ,

wherein Y is norleucine and X is a chemical group attached to the peptide for the purpose of therapeutic intervention at CCK-2 receptor associated diseases, and a pharmaceutically acceptable carrier.

2. The pharmaceutical composition of claim 1 , wherein the therapeutically effective amount is effective for treating CCK-2 receptor positive tumors.

3. The pharmaceutical composition of claim 2 , wherein the CCK-2 receptor positive tumor is selected from the group consisting of medullary thyroid carcinomas (MTC), small cell lung cancers (SCLC), astrocytomes and stromal ovarial tumors.

4. The pharmaceutical composition of claim 1 , wherein X is a chelator for radiometals complexed with a radionuclide.

5. The pharmaceutical composition of claim 4 , wherein the chelator for radiometals is DOTA.

6. The pharmaceutical composition of claim 4 , wherein the radionuclide is selected from the group consisting of 177 Lu, 90 Y and 111 In.

7. The pharmaceutical composition of claim 5 , wherein the mini-gastrin analogue is labelled with 177 Lu.

8. The pharmaceutical composition of claim 1 , wherein X is an optically active chemical compound.

9. The pharmaceutical composition of claim 1 , wherein X is a chemotherapeutic active compound.

10. The pharmaceutical composition of claim 1 , wherein X is a nanoparticle or liposome which has a therapeutic function by itself or which is loaded with an active compound.

11. The pharmaceutical composition of claim 10 , wherein X is a nanoparticle or liposome which is an optically active agent.

12. The pharmaceutical composition of claim 1 , which is formulated for i.v. injection.

13. The pharmaceutical composition of claim 7 , wherein the isotope:peptide ratio is 1:47.

14. The pharmaceutical composition of claim 5 , wherein the radionuclide is selected from the group consisting of 177 Lu, 90 Y and 111 In.

Assignees

• Scherrer Inst Paul

Inventors

• Behe Martin
• Schibli Roger

Classifications

• G01N33/5758

  involving compounds serving as markers for tumours, cancers or neoplasias, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides or metabolites · CPC title

• G01N2333/726

  G protein coupled receptor, e.g. TSHR-thyrotropin-receptor, LH/hCG receptor, FSH · CPC title

• C07K14/595

  Gastrins; Cholecystokinins [CCK] · CPC title

• A61P13/12

  of the kidneys · CPC title

• A61K38/2207

  Gastrins; Cholecystokinins [CCK] · CPC title