DENDRIMER CONJUGATES

• US 20090287005A1
• Filed: 03/12/2009
• Published: 11/19/2009
• Est. Priority Date: 03/12/2008
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Baker, James R. JR., Cheng, Xue-min, Thomas, Thommey P., Huang, Baohua Mark
• Granted Patent: US 8,252,834 B2
• Time in Patent Office: Days
• US Class Current: 549/510
• CPC Class Codes: C07D 305/08 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring atoms

Abstract

The present invention relates to novel therapeutic and diagnostic dendrimers. In particular, the present invention is directed to dendrimer-linker conjugates, methods of synthesizing the same, compositions comprising the conjugates, as well as systems and methods utilizing the conjugates (e.g., in diagnostic and/or therapeutic settings (e.g., for the delivery of therapeutics, imaging, and/or targeting agents (e.g., in disease (e.g., cancer) diagnosis and/or therapy, pain therapy, etc.)). Accordingly, dendrimer-linker conjugates of the present invention may further comprise one or more components for targeting, imaging, sensing, and/or providing a therapeutic or diagnostic material and/or monitoring response to therapy.

Claims

1. A dendrimer conjugate comprising a linker, wherein said linker is conjugated to

a) a G5 PAMAM dendrimer;

b) a targeting agent; and

c) a therapeutic compound.

2. The dendrimer conjugate of claim 1, wherein said G5 PAMAM dendrimer is conjugated to an imaging agent.

3. The dendrimer conjugate of claim 1, wherein said linker is an elimination linker.

4. The dendrimer conjugate of claim 3, wherein said elimination linker is a 1,4 elimination linker.

5. The dendrimer conjugate of claim 3, wherein said elimination linker is a 1,6 elimination linker.

6. The dendrimer conjugate of claim 1, wherein said linker is a cyclization based linker.

7. The dendrimer conjugate of claim 1, wherein said linker is esterase sensitive.

8. The dendrimer conjugate of claim 1, wherein said linker is glucuronidase sensitive.

9. The dendrimer conjugate of claim 1, wherein cleavage of said linker is induced by hypoxia.

10. The dendrimer of claim 9, wherein said linker is indolequinone.

11. The dendrimer conjugate of claim 1, wherein said linker comprises a heteroaromatic nitrogen containing compound.

12. The dendrimer conjugate of claim 1, wherein said linker is a branched self-elimination linker.

13. The dendrimer conjugate of claim 1, wherein said therapeutic agent is Naloxone.

19. The dendrimer conjugate of claim 4, wherein cleavage of said linker is induced by hypoxia.

20. The dendrimer of claim 19, wherein said linker is indolequinone.

14. A dendrimer conjugate comprising:

a) a G5 PAMAM dendrimer;

b) a trigger

c) a linker; and

c) a therapeutic compound.

15. The dendrimer conjugate of claim 14, wherein said trigger is conjugated to said dendrimer and to said linker.

16. The dendrimer conjugate of claim 14, wherein said dendrimer is conjugated to said linker that is conjugated to said trigger and to said therapeutic compound.

17. The dendrimer conjugate of claim 14, wherein an enzyme labile bond links said trigger and said linker.

18. The dendrimer conjugate of claim 17, wherein upon cleavage of said labile bond said linkers self-degrade.