Graft polymers for enhanced intracellular delivery of antisense molecules

Patent metadata

Field	Value
Publication number	US-9574041-B2
Application number	US-201514629013-A
Country	US
Kind code	B2
Filing date	Feb 23, 2015
Priority date	Nov 27, 2007
Publication date	Feb 21, 2017
Grant date	Feb 21, 2017

Abstract

Innovative graft polymers designed for the efficient delivery of antisense molecules into biological cells and for maintaining the biological activity of these molecules while in serum and other aqueous environments are provided. Such polymers may comprise an anionic graft polymer comprising an anionic polymer backbone with pendant carboxylic acid groups and pendant chains comprising amphipathic or hydrophilic polymers covalently bonded to a portion of said pendant carboxylic acid groups. Antisense molecule delivery vectors comprising such polymers in combination with cationic agents for delivery of antisense molecules are also disclosed.

First claim

What is claimed is:

1. A graft polymer comprising:
a backbone comprising a poly(alkyl acrylic acid); and
one or more pendent chains comprising one or more polyetheramine moieties covalently attached to said polymer backbone via said acrylic acid groups;
wherein a majority of the ether groups of said polyetheramine moieties comprise ethylene oxide repeating units; and
wherein said polymer has a graft density between about 1 and about 25 mole percent.

2. The graft polymer of claim 1 , wherein the backbone comprises poly(propyl acrylic acid).

3. The graft polymer of claim 1 having a graft density between about 5 and about 25 mole percent.

4. The graft polymer of claim 1 , wherein said one or more polyetheramine moieties are amphipathic.

5. The graft polymer of claim 1 , wherein said polyetheramine moieties have a molecular weight between about 200 and about 5,000 Daltons.

6. The graft polymer of claim 1 , wherein said polyetheramine moieties further comprise propylene oxide moieties.

7. The graft polymer of claim 2 having a graft density between about 5 and about 25 mole percent.

8. The graft polymer of claim 2 , wherein said one or more polyetheramine moieties are amphipathic.

9. The graft polymer of claim 2 , wherein said polyetheramine moieties have a molecular weight between about 200 and about 5,000 Daltons.

10. The graft polymer of claim 2 , wherein said polyetheramine moieties further comprise propylene oxide moieties.

11. The graft polymer of claim 1 , having a graft density between 10 and 25 mole percent.

12. The graft polymer of claim 2 , having a graft density between 10 and 25 mole percent.

13. The graft polymer of claim 6 , wherein the propylene oxide:ethylene oxide ratio is about 10 to about 31.

14. The graft polymer of claim 10 , wherein the propylene oxide:ethylene oxide ratio is about 10 to about 31.

Assignees

• Univ Rutgers

Inventors

• Devore David
• Roth Charles

Classifications

• C08F265/02 Primary

  on to polymers of acids, salts or anhydrides · CPC title

• C08G81/025

  containing polyether sequences · CPC title

• A61K31/70 Primary

  Carbohydrates; Sugars; Derivatives thereof (sorbitol A61K31/047) · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title

• A61P35/00

  Antineoplastic agents · CPC title