Inhibition of cell-cell binding by lipid assemblies

• US 6,663,886 B2
• Filed: 04/27/2001
• Issued: 12/16/2003
• Est. Priority Date: 02/28/1997
• Status: Expired due to Fees

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Bargatze, Robert F., Nagy, Jon O.
• Primary Examiner(s): Wilson, James O.
• Assistant Examiner(s): Young, Josephine
• Application Number:
  US09/844,681
• Publication Number:
  US 20010036931A1
• Time in Patent Office: 963 Days
• Field of Search: 514/23, 514/24, 514/25, 514/42, 514/53, 514/54, 536/1.11, 536/4.1, 536/18.7, 536/123.1, 536/123.13, 424/450, 424/812
• US Class Current: 424/450
• CPC Class Codes: A61K 9/1273 Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances polymers grafted or coated on phosphatidyl liposomes A61K9/1271, on non-phosphatidyl liposomes A61K9/1272
• CPC Class Codes: Y10S 424/812 Liposome comprising an antibody, antibody fragment, antigen, or other specific or nonspecific immunoeffector

Abstract

This invention relates generally to the field of therapeutic compounds designed to interfere between the binding of ligands and their receptors on cell surface. More specifically, it provides products and methods for inhibiting cell migration and activation using lipid assemblies with surface recognition elements that are specific for the receptors involved in cell migration and activation.

Claims

1. A lipid assembly for inhibiting the binding between a first cell having a receptor and a second cell having a ligand for said receptor, comprising one or more lipid assemblies, wherein said one or more lipid assemblies comprise:

a) lipid monomers, wherein 25-95% of said lipid monomers are unpolymerized;

b) 5-50% surface exposed negatively charged oxyacid groups present on said lipid monomers of said lipid assemblies, wherein said surface exposed negatively charged oxyacid groups meet the anionic binding requirement of said receptor; and

c) 5-20% surface exposed carbohydrates which selectively bind to said receptor.

2. The lipid assembly of claim 1, wherein said surface exposed negatively charged oxyacid groups are selected from the group consisting of carboxyl groups and groups of the form (XO_n)(O⁻

)_p where n+p>

2 and X is an atom capable of binding three or more oxygen atoms.

3. The compositions of claim 2, wherein said X is an atom selected from the group consisting of sulphur and phosphorus.

4. The lipid assembly of claim 1, wherein said one or more surface exposed negatively charged oxyacid groups comprise one or more carboxylate head groups of a fatty acid molecule.

5. The lipid assembly of claim 1, wherein said one or more surface exposed negatively charged oxyacid groups comprise one or more phosphate head groups of a fatty acid molecule.

6. The lipid assembly of claim 5, wherein said one or more phosphate head groups comprises a phosphate head group selected from the group consisting of cardiolipin and dioleoylphosphatidic acid head groups.

7. The lipid assembly of claim 1, wherein said one or more surface exposed negatively charged oxyacid groups comprise one or more sulfate head groups of a fatty acid molecule.

8. The lipid assembly of claim 7, wherein said one or more sulfate head groups comprises 1,4-dihexadecyl ester of sulfosuccinic acid.

9. The lipid assembly of claim 1, wherein said one or more surface exposed carbohydrates comprise neutral carbohydrates.

10. The lipid assembly of claim 9, wherein said one or more surface exposed neutral carbohydrates are covalently attached to said lipid monomers.

11. The lipid assembly of claim 9, wherein said neutral carbohydrates are selected from the group consisting of maltose and lactose.

12. The lipid assembly of claim 1, wherein said one or more surface exposed carbohydrates are covalently attached to said lipid monomers.

13. The lipid assembly of claim 1, wherein said receptor comprises selectin.

14. The lipid assembly of claim 13, wherein said selectin is selected from the group consisting of P-selectin, L-selectin, and E-selectin.

15. The lipid assembly of claim 1, wherein said receptor is selected from the group consisting of lectins, heparin, heparan sulfate, gangliosides, glycans, glycoproteins, and glycolipids.

16. A method for inhibiting the binding between a first cell having a receptor, and a second cell having a ligand for said receptor, comprising:

a) providing;

i) a sample containing said first cell and said second cell;

ii) one or more lipid assemblies, wherein said one or more lipid assemblies comprise;

1) lipid monomers, wherein 25-95% of said lipid monomers are unpolymerized;

2) 5-50% surface exposed negatively charged oxyacid groups present on said lipid monomers of said lipid assemblies, wherein said surface exposed negatively charged oxyacid groups meet the anionic binding requirement of said receptor; and

iii) one or more surface exposed carbohydrates which selectively bind to said receptor; and

b) exposing said lipid assemblies to said first cell.

17. The lipid assembly of claim 16, wherein said 5-50% surface exposed negatively charged oxyacid groups are selected from the group consisting of carboxyl groups and groups of the form (XO_n)(O⁻

)_p where n+p>

2 and X is an atom capable of binding three or more oxygen atoms.

18. The compositions of claim 17, wherein said X is an atom selected from the group consisting of sulphur and phosphorus.

19. The method of claim 16, wherein said first cell and said second cell are involved in cell-cell interactions selected from the group consisting of cell adhesion and cell migration.

20. The method of claim 16, wherein said one or more surface exposed carbohydrates comprise neutral carbohydrates.

21. The method of claim 20, wherein said one or more surface exposed neutral carbohydrates are covalently attached to said lipid monomers.

22. The method of claim 20, wherein said neutral carbohydrates are selected from the group consisting of maltose and lactose.

23. The method of claim 16, wherein said receptor is selected from the group consisting of P-selectin, L-selectin, E-selectin, lectins, heparin, heparan sulfate, gangliosides, glycans, glycoproteins, and glycolipids.

24. A composition for inhibiting the binding between a first cell having a receptor and a second cell having a ligand for said receptor, comprising one or more lipid monomers, wherein 25-95% of said lipid monomers are unpolymerized, further wherein said lipid monomers form lipid assemblies, 5-50% surface exposed negatively charged oxyacid groups present on the lipid monomers of the lipid assemblies, wherein said surface exposed negatively charged oxyacid groups meets the anionic binding requirement of said receptor, one or more surface exposed carbohydrates which selectively bind to said receptor, wherein said one or more surface exposed carbohydrates are selected from the group consisting of sulfated fucooligosaccharide, sialylated fucooligosaccharide, sialylated fucooligosaccharide analog, maltose, lactose, sulfated lactose, sialic acid, fucose, monosaccharides, disaccharides, trisaccharides, tetrasaccharides, and glycopeptides.

25. The lipid assembly of claim 24, wherein said 5-50% surface exposed negatively charged oxyacid groups are selected from the group consisting of carboxyl groups and groups of the form (XO_n)(O⁻

)_p where n+p>

2 and X is an atom capable of binding three or more oxygen atoms.

26. The compositions of claim 25, wherein said X is an atom selected from the group consisting of sulphur and phosphorus.

27. The composition of claim 24, wherein said first cell and said second cell are involved in cell to cell interactions selected from the group consisting of cell adhesion and cell migration.

28. The composition of claim 24, wherein said receptor comprises a selectin selected from the group consisting of P-selectin, L-selectin, and E-selectin.