Graft copolymer of polycationic species and water-soluble polymers, and uses therefor

• US 5,834,556 A
• Filed: 08/29/1996
• Issued: 11/10/1998
• Est. Priority Date: 03/23/1992
• Status: Expired due to Fees

• Current Assignee: ReNeuron Limited (ReNeuron Group Plc)
• Original Assignee: American Bioscience, Inc. (Bristol-Myers Squibb Company)
• Inventors: Soon-Shiong, Patrick, Desai, Neil P., Sandford, Paul A., Heintz, Roswitha E.
• Primary Examiner(s): Nutter, Nathan M.
• Application Number:
  US08/697,885
• Time in Patent Office: 803 Days
• Field of Search: 525/54.1, 525/54.2, 525/54.21, 525/54.23, 525/54.24, 525/54.26, 525/54.3, 525/54.31, 525/60, 525/63, 525/64, 525/70, 527/200, 527/201, 527/207, 527/300, 527/311, 527/312, 527/313, 527/314
• US Class Current: 525/54.1
• CPC Class Codes: A01N 1/021 Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• CPC Class Codes: A61K 2035/128 capsules, e.g. microcapsules
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61K 9/5031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
• CPC Class Codes: C08G 81/00 Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers involving only carbon-to-carbon unsaturated bond reactions C08F299/00 ; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 2533/32 Polylysine, polyornithine
• CPC Class Codes: C12N 2533/40 Polyhydroxyacids, e.g. polymers of glycolic or lactic acid (PGA, PLA, PLGA); Bioresorbable polymers
• CPC Class Codes: C12N 5/0006 Modification of the membrane of cells, e.g. cell decoration
• CPC Class Codes: C12N 5/0012 Cell encapsulation
• CPC Class Codes: C12N 5/0677 Three-dimensional culture, tissue culture or organ culture; Encapsulated cells

Abstract

In accordance with the present invention, there are provided methods to render cells non-adhesive and/or non-immunogenic with respect to macromolecules typically encountered in culture media or in physiological media.

Claims

1. A graft copolymer comprising:

a polycationic species;

at least one water-soluble polymer grafted onto said polycationic species; and

at least one functional group capable of undergoing free radical polymerization.

4. A graft copolymer according to claim 1 wherein said polycationic species is selected from the group consisting of:

polyethyleneimine, polyallylamine, polyetheramine, polyvinylpyridine;

polysaccharides having a positively charged functionality thereon;

polyamino acids selected from the group consisting of poly-L-histidine, poly-im-benzyl-L-histidine, poly-D-lysine, poly-DL-lysine, poly-L-lysine, poly-ε

-CBZ-D-lysine, poly-ε

-CBZ-DL-lysine, poly-ε

-CBZ-L-lysine, poly-DL-ornithine, poly-L-ornithine, poly-δ

-CBZ-DL-ornithine, poly-L-arginine, poly-DL-alanine-poly-L-lysine, poly(-L-histidine, L-glutamic acid)-poly-DL-alanine-poly-L-lysine, poly(L-phenylalanine, L-glutamic acid)-poly-DL-alanine-poly-L-lysine, and poly(L-tyrosine, L-glutamic acid)-poly-DL-alanine-poly-L-lysine;

random copolymers of L-arginine with tryptophan, tyrosine, or serine;

random copolymers of D-glutamic acid with D-lysine,

random copolymers of L-glutamic acid with lysine, ornithine, or mixtures of lysine and ornithine; and

mixtures of any two or more thereof.

5. A graft copolymer according to claim 1 wherein said polycationic species is selected from the group consisting of polylysine and polyornithine.

6. A graft copolymer according to claim 1 wherein said polycationic species has a molecular weight in the range of about 200 up to about 1,000,000.

7. A graft copolymer according to claim 6 wherein said polycationic species has a molecular weight in the range of about 1,000 up to about 100,000.

8. A graft copolymer according to claim 7 wherein said polycationic species has a molecular weight in the range of about 5,000 up to about 50,000.

9. A graft copolymer according to claim 1 wherein said water-soluble polymer has a molecular weight in the range of about 200 up to about 1,000,000.

10. A graft copolymer according to claim 9 wherein said water-soluble polymer has a molecular weight in the range of about 500 up to about 100,000.

11. A graft copolymer according to claim 10 wherein said water-soluble polymer has a molecular weight in the range of about 1,000 up to about 50,000.

12. A graft copolymer according to claim 1 wherein said functional group is covalently attached to said polycationic species.

13. A graft copolymer according to claim 1 wherein said functional group is covalently attached to said water-soluble polymer.

14. A graft copolymer according to claim 1 wherein said functional group is a vinyl group, an acrylate group, or a methacrylate group.

15. A graft copolymer according to claim 1 wherein there are about 10 to about 20 water-soluble polymers attached to said polycationic species.

2. A graft copolymer according to claim wherein said water-soluble polymer is selected from polyalkylene glycol (PAG), polyvinyl alcohol (PVA), poly(hydroxyethyl methacrylate) (pHEMA), polyacrylic acid (PAA), poly(acrylamide), poly(vinyl pyrrolidone) (PVP), poly(ethyl oxazoline) (PEOX), polysaccharides, or copolymers of any two or more thereof.

3. A graft copolymer according to claim 2 wherein said water-soluble polymer is PAG.