Living copolymer-protein/peptide hybrids for biomedical applications

Patent metadata

Field	Value
Publication number	US-9242010-B2
Application number	US-99285409-A
Country	US
Kind code	B2
Filing date	May 18, 2009
Priority date	May 16, 2008
Publication date	Jan 26, 2016
Grant date	Jan 26, 2016

Abstract

Water soluble polymers having formula I: Y-(L 1 ) n1 -(C(O)) n2 —(R 1 ) n3 —R 2 are claimed. The polymers may contain multiple water soluble, immunogenicity reducing moieties and multiple active moieties. The polymers may be linked to a protein, or a peptide having up to twelve amino acids.

First claim

We claim:

1. A polymer having the formula:
Y-(L 1 ) n1 -(C(O)) n2 —(R 1 ) n3 —R 2   I

wherein:
Y represents:

L 1 represents —(CH 2 CH 2 O—) p —C(O)—C(CH 3 ) 2 — or —(OCH 2 CH 2 —) p —C(O)—C(CH 3 ) 2 — wherein p represents a minimum of 1 and a maximum of 20,

or

n1 represents 0 or 1;
n2 represents 0 or 1;
R 1 independently represents:

W independently represents —H, —CH 3 , —COOH, or —CH 2 COOH;
n4a independently represents 0 or 1;
n4 independently represents 0 or 1;
L 2 represents —NH—;
R represents:
(i) C 1 -C 12 alkyl optionally substituted with one or more hydroxyl or oxo substituents, and wherein one or more carbon atoms in the alkyl chain is optionally substituted with a heteroatom selected from the group consisting of —O—, —S—, and —NH—; (ii) phenyl or biphenyl, (iii) a carbocyclic non-aromatic ring having 5-7 carbon atoms; (iv) an aromatic heterocyclic ring having five or six atoms wherein at least one of the ring carbon atoms is substituted by a heteroatom selected from the group consisting of O, S, or NH, and (v) a non-aromatic heterocyclic ring having 5-7 carbon atoms wherein at least one of the ring carbon atoms is substituted by a heteroatom selected from the group consisting of O, S, or NH;

A represents (A 1 ) n and (A 2 ) m ;
A 1 represents glucose;
A 2 represents NIRF dye;
n and m independently represent 2 to about 60;
n3 represents n+m; and
R 2 represents H, an a straight chain or branched alkyl group having 1-6 carbon atoms, Cl or Br.

2. A polymer according to claim 1 , wherein L 1 results from the chain initiation step of the polymerization process.

3. A polymer according to claim 1 , wherein p represents 2-4.

4. A polymer according to claim 1 , wherein p represents 3.

5. A polymer according to claim 1 , wherein R represents —(CH 2 CH 2 O—) p — or —(OCH 2 CH 2 —) p —, and p represents a minimum of 1 and a maximum of 20.

6. A polymer according to claim 1 , wherein Y is replaced by E-X, and wherein E represents a protein or a peptide having up to twelve amino acids, and
X is

7. A polymer according to claim 6 , wherein E is a chromophore, a radioactive label, a biologically active molecule or an MRI imaging agent.

8. A polymer according to claim 6 , wherein E is a targeting protein or peptide.

9. A polymer according to claim 8 , wherein E is selected from the group consisting of an antibody, HIV Tat, RGD peptides, avidin, and streptavidin.

10. A polymer according to claim 9 , wherein E is a primary, secondary, or monoclonal antibody.

11. A polymer according to claim 9 , wherein the antibody is genetically or chemically modified.

12. A polymer according to claim 11 , wherein the antibody is chimerized or humanized.

13. A polymer according to claim 6 , wherein E is an enzyme.

14. A polymer according to claim 13 , wherein the enzyme is horseradish peroxidase, beta-galactosidase or luciferase.

15. A polymer according to claim 6 , wherein E is a bionanoparticle.

16. A polymer according to claim 15 , wherein the bionanoparticle is a virus, ferritin, or apoferritin.

17. A polymer according to claim 16 , wherein the bionanoparticle is a virus, and the virus is tobacco mosaic virus or cauliflower mosaic virus.

18. A polymer according to claim 16 , wherein the virus is genetically or chemically modified.

19. A polymer according to claim 18 , wherein the virus is an empty capsid.

20. A polymer according to claim 6 , wherein E is a protein selected from the group consisting of Protein A, Protein G, Protein L, BSA, and ovalbumen.

21. A polymer according to claim 6 , wherein E is hepatitis B surface antigen.

22. A polymer according to claim 6 , wherein E is a therapeutic protein.

23. A polymer according to claim 22 , wherein the therapeutic protein is erythropoietin, human growth hormone, and insulin.

24. A polymer according to claim 1 , wherein n is 30 to 60 and m is 2 to 20.

25. A polymer represented by the following formula:

wherein:
Y represents:

A represents (A 1 ) n and (A 2 ) m ;
A 1 represents glucose;
A 2 represents NIRF dye;
n is 30 to 60;
m is 2 to 20; and
n3 represents n+m.

Assignees

• Raja Krishnaswami
• Shi Wei
• Dolai Sukanta
• Averick Saadyah
• L Amoreaux William
• Banerjee Probal
• Univ City New York Res Found

Inventors

• Raja Krishnaswami
• Shi Wei
• Dolai Sukanta
• Averick Saadyah
• L Amoreaux William
• Banerjee Probal

Classifications

• A61K49/0032 Primary

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

• A61K49/0054

  Macromolecular compounds, i.e. oligomers, polymers, dendrimers · CPC title

• A61K49/0056

  Peptides, proteins, polyamino acids · CPC title

• A61K47/48215

  Human Necessities · mapped topic

• A61K49/12

  Macromolecular compounds · CPC title