Chemical structures for localized delivery of therapeutic agents

Patent metadata

Field	Value
Publication number	US-2016120987-A1
Application number	US-201414899041-A
Country	US
Kind code	A1
Filing date	Jun 18, 2014
Priority date	Jun 19, 2013
Publication date	May 5, 2016
Grant date	—

Abstract

The present invention provides a method for selective delivery of a therapeutic or diagnostic agent to a targeted organ or tissue by implanting a biocompatible solid support in the patient being linked to a first binding agent, and administering a second binding agent to the patient linked to the therapeutic or diagnostic agent, such that the therapeutic or diagnostic agent accumulates at the targeted organ or tissue.

First claim

What is claimed is:

1 . A method for selectively delivering an effective amount of a therapeutic or diagnostic agent to a first location of a targeted organ or tissue in a patient, comprising the steps of:
(a) implanting a biocompatible solid support in the patient at the first location of the targeted organ or tissue, wherein the solid support is linked to a first binding agent, and wherein the first location of the targeted organ or tissue cannot be selectively targeted by chemical or biological targeting agents over other locations of the targeted organ or tissue in the patient; and (b) administering to the patient the therapeutic or diagnostic agent linked to a second binding agent, such that the first and second binding agents bind to one another upon contact, thereby selectively delivering the effective amount of the therapeutic or diagnostic agent to the first location of the targeted organ or tissue in the patient.

2 . The method of claim 1 , wherein the solid support comprises a hydrogel.

3 . The method of claim 1 , wherein the solid support comprises alginate.

4 . The method of claim 1 , wherein the first and second binding agents are each independently selected from the group consisting of cyclooctene, tetrazine, azide and alkyne.

5 . The method of claim 1 , wherein the first and second binding agents are each independently selected from the group consisting of trans-cyclooctene and 1,2,4,5-tetrazine, such that one of the binding agents is trans-cyclooctene and the other is 1,2,4,5-tetrazine.

6 . The method of claim 1 , wherein the targeted organ or tissue is bone.

7 . The method of claim 1 , wherein the concentration of the therapeutic or diagnostic agent at the first location of the targeted organ or tissue is greater than the concentration elsewhere in the patient.

8 . The method of claim 1 , wherein the therapeutic agent is vancomycin.

9 . A method of treating a disease or condition in a patient, comprising administering to the patient a therapeutic agent linked to a first binding agent, such that when the first binding agent contacts a second binding agent at the site of the disease or condition, the first and second binding agents bind to one another forming a therapeutically effective amount of the therapeutic agent at the site of the disease or condition, wherein the amount of the therapeutic agent administered to the patient is less than the therapeutically effective amount administered to the patient in the absence of the second binding agent.

10 . The method of claim 9 , wherein the disease or condition is osteomyelitis.

11 . The method of claim 9 , wherein the therapeutic agent is vancomycin.

12 . A composition comprising:
a biocompatible solid support; and at least one cyclooctene linked to the biocompatible solid support.

13 . The composition of claim 12 , wherein the composition further comprises a linker covalently linking each cyclooctene to the biocompatible solid support.

14 . The composition of claim 12 , wherein the solid support comprises a hydrogel.

15 . The composition of claim 12 , wherein the solid support comprises alginate.

16 . The composition of claim 12 , wherein the composition has the structure of the formula:

17 . A composition comprising:
a therapeutic or diagnostic agent; a 1,2,4,5-tetrazine; and a linker, covalently linking the therapeutic or diagnostic agent to the 1,2,4,5-tetrazine.

18 . The composition of claim 17 , wherein the composition has the structure of the formula selected from the group consisting of:

Assignees

• Univ California
• Alchemical Res Holdings Llc

Inventors

• Mejia Oneto Jose Manuel
• Al-Rashid Ziyad F

Classifications

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P19/08

  for bone diseases, e.g. rachitism, Paget's disease · CPC title

• A61P19/00

  Drugs for skeletal disorders · CPC title

• A61K47/545

  Heterocyclic compounds (A61K47/558 takes precedence) · CPC title