Trifunctional constructs with tunable pharmacokinetics useful in imaging and anti-tumor therapies

Patent metadata

Field	Value
Publication number	US-2024050599-A1
Application number	US-202318113206-A
Country	US
Kind code	A1
Filing date	Feb 23, 2023
Priority date	Jun 23, 2016
Publication date	Feb 15, 2024
Grant date	—

Abstract

The present technology provides compounds, as well as compositions including such compounds, useful for imaging and/or treatment of a glioma, a breast cancer, an adrenal cortical cancer, a cervical carcinoma, a vulvar carcinoma, an endometrial carcinoma, a primary ovarian carcinoma, a metastatic ovarian carcinoma, a non-small cell lung cancer, a small cell lung cancer, a bladder cancer, a colon cancer, a primary, gastric adenocarcinoma, a primary colorectal adenocarcinoma, a renal cell carcinoma, and/or a prostate cancer.

First claim

1 . A compound comprising: a tumor-binding domain wherein the tumor-binding domain binds to somatostatin peptide receptor-2 (SSTR2), an albumin-binding domain, and a cytocidal or cytostatic therapeutic agent, wherein the tumor-binding domain comprises an active site that is distal to and sterically unimpeded by the albumin-binding domain and the therapeutic agent.

2 . (canceled)

3 . The compound of claim 2 , wherein the tumor-binding domain binds to the tumor associated molecular target with moderate to high affinity.

4 . The compound of claim 1 , wherein the cytocidal or cytostatic therapeutic agent is a toxin, a venom, a metabolic poison, a chemotherapeutic agent, an auger electron-emitting radionuclide, a beta-emitting radionuclide, or an alpha-emitting radionuclide.

5 . A compound comprising:
a multi-targeted agent having a plurality of sterically unimpeded targeting domains, comprising a first targeting domain comprising a blood-protein binding domain having specific affinity for binding human serum albumin in the range of about 0.25 to 50 micromolar, and a second targeting domain comprising a tumor-binding domain having specific affinity for a tumor associated molecular target in the range of about 0.1 to 75 nanomolar; wherein the tumor associated molecular target is somatostatin peptide receptor-2 (SSTR2); and a therapeutic domain comprising a cytocidal or cytostatic therapeutic agent.

6 . (canceled)

7 . The compound of claim 6 , wherein the tumor-binding domain binds to the tumor associated molecular target with moderate to high affinity.

8 . The compound of claim 5 , wherein the cytocidal or cytostatic therapeutic agent is a toxin, a venom, a metabolic poison, a chemotherapeutic agent, an auger electron-emitting radionuclide, a beta-emitting radionuclide, or an alpha-emitting radionuclide.

9 . The compound of claim 5 , wherein the therapeutic domain comprises a covalently conjugated chelating agent or a covalently conjugated polyaza polycarboxylic macrocycle.

10 . The compound of claim 9 , wherein the therapeutic domain further comprises an auger electron-emitting radionuclide, a beta-emitting radionuclide, or an alpha-emitting radionuclide.

11 .- 12 . (canceled)

13 . The compound of claim 5 , wherein the blood-protein binding domain is selected from one or more of myristic acid, a substituted or unsubstituted indole-2-carboxylic acid, a substituted or unsubstituted thioamide, a substituted or unsubstituted 4-oxo-4-(5,6,7,8-tetrahydronaphthalen-2-yl)butanoic acid, a substituted or unsubstituted naphthalene acylsulfonamide, a substituted or unsubstituted diphenylcyclohexanol phosphate ester, a substituted or unsubstituted 4-iodophenylalkanoic acid, a substituted or unsubstituted 3-(4-iodophenyl)propionic acid, a substituted or unsubstituted 2-(4-iodophenyl)acetic acid, or a substituted or unsubstituted 4-(4-iodophenyl)butanoic acid.

14 .- 17 . (canceled)

Assignees

• Univ Cornell

Inventors

• Babich John W
• Kelly James M
• Amor-Coarasa Alejandro
• Ponnala Shashikanth

Classifications

• A61K51/0482 Primary

  chelates from cyclic ligands, e.g. DOTA · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K51/0497

  conjugates with a carrier being an organic compounds · CPC title

• A61K51/0402

  carboxylic acid carriers, fatty acids (amino acids A61K51/0406) · CPC title