Protein-poly(2-oxazoline) conjugates for enhanced cellular delivery and transport across biological barriers

Patent metadata

Field	Value
Publication number	US-9974866-B2
Application number	US-201113634717-A
Country	US
Kind code	B2
Filing date	Apr 7, 2011
Priority date	Apr 7, 2010
Publication date	May 22, 2018
Grant date	May 22, 2018

Abstract

The present invention provides polymer-polypeptide conjugates comprising a poly(2-oxazoline) amphiphilic block copolymer linked to a polypeptide and methods of use thereof.

First claim

What is claimed is:

1. A polymer-polypeptide conjugate comprising at least one amphiphilic block copolymer linked to at least one polypeptide,
wherein said amphiphilic block copolymer comprises at least one hydrophilic segment and at least one hydrophobic segment, wherein said hydrophilic segment is a hydrophilic poly(2-oxazoline), wherein said hydrophobic segment is a hydrophobic poly(2-oxazoline), and wherein said amphiphilic block copolymer comprises the formula:

wherein x and y are independently selected between 10 and about 100; one of R 1 and R 2 is selected from the group consisting of —H, —OH, —NH 2 , —SH, —CH 3 , —CH 2 CH 3 , and an alkyl comprising 1 or 2 carbon atoms; and the other R group is an alkyl or an aryl.

2. The conjugate of claim 1 , wherein said hydrophilic segment is poly(2-methyl-2-oxazoline) or poly(2-ethyl-2-oxazoline).

3. The conjugate of claim 1 , wherein said hydrophobic segment is poly(2-butyl-2-oxazoline).

4. The conjugate of claim 1 , wherein said polypeptide is a therapeutic agent, a diagnostic agent, or a cosmetic agent.

5. The conjugate of claim 1 , wherein said amphiphilic block copolymer is linked to said polypeptide via a linker.

6. The conjugate of claim 1 , wherein said amphiphilic block copolymer is covalently linked to said polypeptide.

7. The conjugate of claim 1 , wherein said amphiphilic copolymer comprises the formula:

wherein R 1 is selected from the group consisting of —H, —OH, —NH 2 , —SH, —CH 3 , —CH 2 CH 3 , and an alkyl comprising 1 or 2 carbon atoms; and R 2 is an alkyl or an aryl.

8. A composition comprising at least one conjugate of claim 1 and at least one carrier.

9. The conjugate of claim 1 , wherein said polypeptide is linked to a terminus of said amphiphilic block copolymer.

10. The conjugate of claim 5 , wherein said polypeptide is linked to a terminus of said amphiphilic block copolymer via said linker.

11. The conjugate of claim 1 , wherein said hydrophilic segment is poly(2-methyl-2-oxazoline) or poly(2-ethyl-2-oxazoline) and wherein said hydrophobic segment is poly(2-butyl-2-oxazoline).

12. The conjugate of claim 11 , wherein said amphiphilic block copolymer is (2-methyl-2-oxazoline) 50 -(2-butyl-2-oxazoline) 20 or (2-ethyl-2-oxazoline) 50 -(2-butyl-2-oxazoline) 20 .

13. The conjugate of claim 11 , wherein said polypeptide is linked to a terminus of said amphiphilic block copolymer via said linker and wherein said polypeptide is superoxide dismutase.

14. The conjugate of claim 12 , wherein said polypeptide is linked to a terminus of said amphiphilic block copolymer via said linker and wherein said polypeptide is superoxide dismutase.

15. The conjugate of claim 13 , wherein said linker is non-biodegradable.

16. The conjugate of claim 14 , wherein said linker is non-biodegradable.

17. The conjugate of claim 5 , wherein said linker is non-biodegradable.

18. The conjugate of claim 1 , wherein said polypeptide is linked to a terminus of said hydrophobic segment of said amphiphilic block copolymer.

19. The conjugate of claim 5 , wherein said polypeptide is linked to a terminus of said hydrophobic segment of said amphiphilic block copolymer via said linker.

20. The conjugate of claim 11 , wherein said polypeptide is linked to the terminus of said poly(2-butyl-2-oxazoline).

Assignees

• Kabanov Alexander V
• Tong Jing
• Univ Nebraska

Inventors

• Kabanov Alexander V
• Tong Jing

Classifications

• A61P9/12

  Antihypertensives · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61K47/59 Primary

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes · CPC title

• A61K38/00

  Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) · CPC title