Novel liposome compositions
AssigneeMebiopharm Co., Ltd.
InventorsKazushi Okada, Tadayuki Ibuki, Donghyun Kim, Tadashi Fujisawa
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Abstract
The present disclosure provides lipid-containing compositions, including targeted liposomes encapsulating drug, and pharmaceutical formulations thereof, as well as methods for the making and using the lipid-containing compositions, including the use of the targeted liposomes in the treatment of cancer and other diseases.
Claims254
A targeted liposome comprising one or more phospholipids, an N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, a targeting factor-modified N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, an encapsulated drug or labeled compound and, optionally, at least one additional lipid,
- wherein the targeting factor-modified N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine comprises a targeting ligand linked to a second N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine;
- and
- wherein
- the N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 1,
- the second N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 3,
- wherein R1, R2, R5 and R6 are each, independently, an acyl group, and
- m and p are, independently, an integer from 1 to 10;
- and,
- wherein the liposome does not comprise a non-derivatized phosphatidyl ethanolamine or polyethylene glycol, and wherein the targeting ligand is not an intact antibody.
A transferrin-modified N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, where the N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 3,
- wherein R5 and R6 are each, independently, an acyl group and p is an integer from 1 to 10,
- and transferrin is linked to the N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine.
A blank liposome comprising one or more phospholipids, an N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, a targeting factor-modified N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, and,
- optionally, at least one additional lipid,
- wherein the targeting factor-modified N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine comprises a targeting ligand linked to a second N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine;
- and
- wherein
- the N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 1,
- the second N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 3,
- wherein R1, R2, R5 and R6 are each, independently, an acyl group, and
- m and p are, independently, an integer from 1 to 10;
- and,
- wherein the liposome does not comprise a non-derivatized phosphatidyl ethanolamine or polyethylene glycol, and wherein the targeting ligand is not an intact antibody.
The blank liposome according to claim or 89, wherein the targeting ligand is transferrin.
A lipid mixture comprising a mixture of one or more phospholipids, an N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, a succinimidyl ester of an N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, and, optionally, at least one additional lipid,
- wherein
- the N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 1,
- the succinimidyl ester of the N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanol amine is represented by Formula 2,
- wherein R1, R2, R3 and R4 are each, independently, an acyl group,
- m and n are, independently, an integer from 1 to 10;
- and,
- wherein the mixture does not comprise a non-derivatized phosphatidyl ethanolamine or polyethylene glycol.
A lipid mixture comprising a mixture of one or more phospholipids, an N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, a targeting factor-modified N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, and, optionally, at least one additional lipid,
- wherein
- the N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 1,
- the targeting factor-modified N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine comprises a targeting ligand linked to a second N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine;
- and
- wherein the second N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 3,
- wherein R1, R2, R5 and R6 are each, independently, an acyl group,
- m and p are, independently, an integer from 1 to 10;
- and,
- wherein the mixture does not comprise a non-derivatized phosphatidyl ethanolamine or polyethylene glycol, and wherein the targeting ligand is not an intact antibody.
A liposome-containing composition comprising liposomes comprising one or more phospholipids, an N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, a succinimidyl ester of an N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, and, optionally, at least one additional lipid,
- wherein
- the N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 1,
- the succinimidyl ester of the N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 2,
- wherein R1, R2, R3 and R4 are each, independently, an acyl group,
- m and n are, independently, an integer from 1 to 10;
- and,
- wherein the composition does not comprise a non-derivatized phosphatidyl ethanolamine or polyethylene glycol.
A liposome-containing composition comprising liposomes comprising one or more phospholipids, an N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, a targeting factor-modified N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine, and, optionally, at least one additional lipid,
- wherein
- the N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 1,
- the targeting factor-modified N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine comprises a targeting ligand linked to a second N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine;
- and
- wherein the second N-(ω)-dicarboxylic acid-derivatized phosphatidyl ethanolamine is represented by Formula 3,
- wherein R1, R2, R5 and R6 are each, independently, an acyl group,
- m and p are, independently, an integer from 1 to 10;
- and,
- wherein the composition does not comprise a non-derivatized phosphatidyl ethanolamine or polyethylene glycol, and wherein the targeting ligand is not an intact antibody.
Dependencies are inferred from the claim text.