Homing agents

Patent metadata

Field	Value
Publication number	US-9849201-B2
Application number	US-201414270061-A
Country	US
Kind code	B2
Filing date	May 5, 2014
Priority date	May 3, 2013
Publication date	Dec 26, 2017
Grant date	Dec 26, 2017

Abstract

The present disclosure provides peptide constructs for diagnostic imaging and therapeutic applications, using pegylated peptides which exhibit specific binding for a target molecule of interest, such as a biomarker of a disease or disorder.

First claim

What is claimed is:

1. A p-armed multimer, each arm of the multimer comprising:
a polymer comprising n PEG monomers, wherein n is at least 2;
a linker comprising His-His-Glu; and
a homing molecule selected from the group consisting of an antibody, an aptamer, and a peptide, wherein the homing molecule binds a biomarker of thrombosis,

wherein the homing molecule is linked to the C-terminus of the linker, and the polymer is linked via an amino acid side chain of the linker; and
wherein p is at least 3, and each arm of the multimer is bound to the other arms of the multimer via an end of the polymer not attached to the linker;
wherein the p-armed multimer further comprises at least one diagnostic and/or therapeutic agent attached to an N-terminus of the linker of that arm, wherein the at least one diagnostic agent or therapeutic agent is a radioisotope of technetium or a radioisotope of rhenium.

2. A p-armed multimer of claim 1 , wherein the biomarker of thrombosis is selected from the group consisting of fibrin and ICAM.

3. A p-armed multimer of claim 1 , wherein the radionuclide is selected from the group consisting of 99m Tc, 186 Re, and 188 Re.

4. A p-armed multimer of claim 1 , comprising a diagnostic agent on at least one arm and a therapeutic agent on at least one other arm.

5. A radiopharmaceutical composition comprising a p-armed multimer of claim 1 , together with a pharmaceutically-acceptable carrier.

6. A method for detecting intradevice thrombus in a subject having an implanted mechanical circulation assist device, the method comprising:
(a) administering into the bloodstream of the subject an effective amount of the p-armed multimer of claim 1 ;
(b) allowing the p-armed multimer to bind thrombus; and
(c) detecting a signal from the radioisotope of the p-armed multimer localized at a site of thrombus.

7. The method of claim 6 , wherein the method further comprises quantifying intradevice thrombus by: (d) determining the amount of p-armed multimer localized at a site of thrombus from the signal detected, wherein the amount of p-armed multimer is indicative of the size of the thrombus.

8. A p-armed multimer of claim 1 , wherein the homing molecule is attached to the C-terminus of the linker via a hydrophilic moiety.

9. A p-armed multimer of claim 1 , wherein n is 2 to 60.

10. A p-armed multimer, each arm of the multimer comprising:
a polymer comprising n PEG monomers, wherein n is at least 2;
a linker comprising His-His-Glu; and
a homing molecule that is an antibody, wherein the homing molecule binds a target molecule;

wherein the homing molecule is linked to the C-terminus of the linker, and the polymer is linked via an amino acid side chain of the linker; and
wherein p is at least 3, and each arm of the multimer is bound to the other arms of the multimer via an end of the polymer not attached to the linker;
wherein the p-armed multimer further comprises at least one diagnostic and/or therapeutic agent attached to an N-terminus of the linker of that arm, wherein the at least one diagnostic agent or therapeutic agent is a radioisotope of technetium or a radioisotope of rhenium.

11. A p-armed multimer of claim 10 , wherein the target molecule is a biomarker of thrombosis.

12. A p-armed multimer of claim 10 , wherein the target molecule is selected from the group consisting of fibrin and ICAM.

13. A p-armed multimer of claim 10 , wherein n is 2 to 60.

14. A p-armed multimer of claim 10 , wherein the N-terminus of the homing molecule is attached to the C-terminus of the linker using a hydrophilic moiety.

15. A p-armed multimer, each arm of the multimer comprising:
a polymer comprising n PEG monomers, wherein n is at least 2;
a linker comprising His-His-Glu; and
a homing molecule comprising SEQ ID NO: 1;

wherein the homing molecule is linked to the C-terminus of the linker, and the polymer is linked via an amino acid side chain of the linker; and
wherein p is at least 3, and each arm of the multimer is bound to the other arms of the multimer via an end of the polymer not attached to the linker;
wherein the p-armed multimer further comprises at least one diagnostic and/or therapeutic agent attached to an N-terminus of the linker of that arm, wherein the at least one diagnostic agent or therapeutic agent is a radioisotope of technetium or a radioisotope of rhenium.

16. A p-armed multimer of claim 15 , wherein the homing molecule is attached to the C-terminus of the linker via a hydrophilic moiety.

17. A p-armed multimer of claim 15 , wherein n is 2 to 60.

Assignees

• Univ Washington
• Univ Washington

Inventors

• Lanza Gregory M
• Achilefu Samuel A
• Hufang Cui Grace

Classifications

• A61K49/0032

  Methine dyes, e.g. cyanine dyes · CPC title

• A61K51/088 Primary

  conjugates with carriers being peptides, polyamino acids or proteins (antibodies A61K51/10) · CPC title

• A61K49/124

  dendrimers, dendrons, hyperbranched compounds · CPC title

• A61K51/065

  conjugates with carriers being macromolecules · CPC title

• A61K49/0056

  Peptides, proteins, polyamino acids · CPC title