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EP0036277A2 Expired / Lapsed EP ⏱️ 0.0 years remaining

Covalently bonded liposome-protein-compositions and method of producing them

Assignee: University of California Berkeley
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Filing: 1981-03-06
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Granted: —
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Expires: 2001-03-06
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Abstract

Abstract Activated liposome having various material encapsulated by outer surfaces thereof are disclosed. The outer surfaces include lipid molecules, at least some of which have been modified by an oxidation reaction and which function as covalent binding sites for a variety of proteins, most particularly for IgG. When biologically active proteins are covalently bound, or coupled, to the activated liposomes, the encapsulated materials remain captured within the activated liposomes, and the coupled proteins retain a significant amount of biological activity.

Inventors

  • 👤 Demetrios P. Papahadjopoulos
  • 👤 Timothy D. Heath

Bibliographic Details

Application Number —
Jurisdiction EP
Data Source google_patents
Last Synchronized 2026-10-23 14:16
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/10; A61K9/127; A61K9/1271; A61K39/00; A61K39/395; A61K39/44; A61K47/00; A61K47/50; A61K47/69; A61K47/6905; A61K47/6911; A61K47/6913

Claims Analysis

Total Claims: 15
Claim 1
Independent Claim 58 words
A method for producing activated liposomes characterised in that liposomes with outer surfaces including a plurality of lipid molecules, said lipid molecules having polar heads and non-polar tails and at least some of said polar heads with oxidisable groups thereat; are contacted with an oxidizing reagent to produce activated liposomes, the oxidisable groups being oxidized to aldehyde moieties.
Claim 2
Independent Claim 58 words
A method for producing activated liposomes characterised in that liposomes with outer surfaces including a plurality of lipid molecules, said lipid molecules having polar heads and non-polar tails and at least some of said polar heads with oxidisable groups thereat; are contacted with an oxidizing reagent to produce activated liposomes, the oxidisable groups being oxidized to aldehyde moieties.
Claim 3
Dependent Claim 39 words
A method according to claim 1 wherein at least some of said polar heads with oxidisable groups thereat have vicinal hydroxyl groups and are selected from the group consisting of lactosylceramide, galactocerebroside, trihexosylceramide, phosphatidylglycerol, phosphatidylinositol, gangliosides and mixtures thereof.
Claim 4
Dependent Claim 21 words
A method according to claim 2 wherein said lipid molecules are a mixture of lipids, the mixture including phosphatidylcholine or sphingomyelin.
Claim 5
Dependent Claim 42 words
A method according to claim 2 or claim 3 wherein said lipid molecules having said polar heads with vicinal hydroxyl groups are in an amount of at least about 10 molar percent with respect to a total of said mixture of lipids.
Claim 6
Independent Claim 29 words
A method according to any one of the preceding claims wherein said lipid molecules define a bi- molecular layer and said liposomes include cholesterol disposed within said bi-molecular layer.
Claim 7
Independent Claim 25 words
A method according to any one of claims 1 to 4 wherein said liposomes of the providing step are unilamellar vesicles having substantially equivalent diameters.
Claim 8
Independent Claim 22 words
A method according to any one of the preceding claims wherein said oxidizing reagent is a periodate reagent or is lead tetraacetate.
Claim 9
Dependent Claim 39 words
A method according to claim 7 wherein the contacting step is conducted in a polar solvent and said oxidizing reagent is sodium periodate in a ratio with respect to the lipid molecules of from about 1.5:1 to about 6:1.
Claim 10
Independent Claim 64 words
A method for coupling proteins to liposomes by: activating liposomes, by a method according to any one of the preceding claims and admixing a protein having at least one primary or secondary amino group with said activated liposomes, the admixing being conducted in a polar solvent in the presence of a sufficient quantity of sodium cyanoborohydride to bind said protein to said activated liposomes.
Claim 11
Dependent Claim 17 words
A method according to claim 9 wherein said protein has at least about 20 lysyl moieties therealong.
Claim 12
Dependent Claim 15 words
A method according to claim 9 wherein said protein is IgG or F(ab'] 2 .
Claim 13
Dependent Claim 60 words
A method according to claim 9, claim 10 or claim 11 wherein the protein is an antibody having an original, determinable antigen binding capacity prior to the admixing step, and said protein bound to said liposomes from the admixing step has an antigen binding capacity of not less than about 10% with respect to said original, determinable antigen binding capacity.
Claim 14
Dependent Claim 67 words
Activated liposomes comprising: a plurality of unilamellar liposomes each having a substantially predetermined diameter, said liposomes each including a substantially predetermined total quantity of lipid molecules, at least some of said lipid molecules providing a plurality of covalent binding sites on substantially each liposome, said binding sites capable of covalently binding at least about 40 micrograms of IgG per micromole of said total quantity of lipid molecules.
Claim 15
Dependent Claim 67 words
Activated liposomes comprising: a plurality of unilamellar liposomes each having a substantially predetermined diameter, said liposomes each including a substantially predetermined total quantity of lipid molecules, at least some of said lipid molecules providing a plurality of covalent binding sites on substantially each liposome, said binding sites capable of covalently binding at least about 40 micrograms of IgG per micromole of said total quantity of lipid molecules.

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