Graft copolymers of polycationic species and water-soluble polymers, and use therefor

• US 5,578,442 A
• Filed: 03/23/1992
• Issued: 11/26/1996
• Est. Priority Date: 03/23/1992
• Status: Expired due to Term

• 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): Gitomer, Ralph J.
• Application Number:
  US07/856,137
• Time in Patent Office: 1,709 Days
• Field of Search: 435/1, 435/41, 435/240.1, 435/240.22, 435/962, 435/178, 435/182, 264/4.1, 264/4.32, 264/4.7, 525/54.1, 525/54.2
• US Class Current: 435/1.1
• 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
• 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. The invention method comprises contacting cells with an effective amount of a composition comprising a polycationic species having water-soluble polymer chains grafted thereon.

Claims

1. A method to render cells non-adhesive, said method comprising directly contacting a surface of said cells with an effective amount of a composition comprising a polycationic species having water-soluble polymer chains grafted thereon.

2. A method according to claim 1 wherein said water-soluble polymer is selected from polyethylene glycol (PEG), 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 method according to claim 1 wherein said polycationic species has grafted thereon at least one water-soluble polymer chain per chain of said polycationic species.

4. A method according to claim 3 wherein said water-soluble polymer is polyethylene glycol.

5. A method according to claim 1 wherein either the water-soluble polymer, or the polycationic species, or both contain at least one functional group which is susceptible to free radical polymerization.

6. A method according to claim 5 wherein said composition is further subjected to free radical polymerization conditions.

7. A method according to claim 1 wherein said polycationic species is selected from one or more of:

polyethyleneimine, polyallylamine, polyetheramine, polyvinylpyridine,

polysaccharides having a positively charged functionality thereon,

polyamino acids selected from;

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;

or

poly(L-tyrosine, L-glutamic acid)-poly-DL-alanine-poly-L-lysine;

or

random copolymers of;

L-arginine with tryptophan, tyrosine, or serine;

D-glutamic acid with D-lysine;

or

L-glutamic acid with lysine, ornithine, or mixtures thereof.

8. A method according to claim 1 wherein said polycationic species is selected from polylysine or polyornithine.

9. A method according to claim 1 wherein said cells to be rendered non-adhesive are selected from islets, thyroid cells, adrenal cells, dopamine secreting cells, hepatocytes, or human T-lymphoblastoid cells sensitive to the cytopathic effects of HIV.

10. The cells produced by the method of claim 1.

11. A method to render cells non-immunogenic, said method comprising directly contacting a surface of said cells with a composition comprising a polycationic species having water-soluble polymer chains grafted thereon.

12. A method according to claim 11 wherein said polycationic species has grafted thereon at least one water-soluble polymer chain per chain of said polycationic species.

13. A method according to claim 12 wherein said water-soluble polymer is polyethylene glycol.

14. A method according to claim 11 wherein said cells to be rendered non-immunogenic are selected from islets, thyroid cells, adrenal cells, dopamine secreting cells, hepatocytes, or human T-lymphoblastoid cells sensitive to the cytopathic effects of HIV.

15. The cells produced by the method of claim 11.

16. A method for associating water-soluble polymer with a cell surface, said method comprising:

grafting water-soluble polymer onto a polycationic resin to produce a copolymer, and thereafter

directly contacting said cell surface with an effective amount of said copolymer.

17. A method according to claim 16 wherein said copolymer comprises a polycation having grafted thereon at least one water-soluble polymer chain per chain of said polycationic resin.

18. Cells having a modified cell surface which is non-adhesive with respect to mediators of immune response, wherein the surface of said cells has been modified by directly contacting said surface with a composition comprising a polycationic species having water-soluble polymer chains grafted thereon.