Therapeutic liposome composition and method of preparation

a technology of liposome and composition, which is applied in the direction of biochemistry apparatus and processes, pharmaceutical non-active ingredients, enzymes, etc., can solve the problems of difficult to react all the activated ends with a ligand, lack of flexibility in designing a therapeutic composition, etc., and achieve the effect of tailoring and designing for a particular patien

Inactive Publication Date: 2005-06-23
ALZA CORP +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0008] Accordingly, it is an object of the invention to provide a therapeutic liposome composition that is readily tailored and designed for a particular patient.

Problems solved by technology

The disadvantage to this approach is the difficulty in reacting all of the activated ends with a ligand.
This approach has the disadvantage that some of the valuable ligand faces the inner aqueous compartment of the liposome and is unavailable for interaction with the intended target.
Both approaches suffer from a lack of flexibility in designing a therapeutic composition that is specific for a target cell for a specific patient.

Method used

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  • Therapeutic liposome composition and method of preparation
  • Therapeutic liposome composition and method of preparation
  • Therapeutic liposome composition and method of preparation

Examples

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example 1

Preparation of Pre-formed Liposomes and Insertion of Targeting Conjugate

[0127] Liposomes were prepared by mixing partially hydrogenated soy-bean phosphatiylcholine (PHPC, iodine value of 35, Lippid (Ludwigshafen, Germany)), cholesterol (Croda (Fullerton, Calif.)) and mPEG-DSPE (prepared as described in Zalipsky, S., et al., Bioconjugate Chemistry, 4:296-299 (1993)) at a molar ratio of 55:40:3 in chloroform and / or methanol in a round bottom flask. The solvents were removed by rotary evaporation, and the dried lipid film produced was hydrated with either sodium phosphate buffer (10 mM, 140 mM NaCl, pH 7) or HEPES buffer (25 mM, 150 mM NaCl, pH 7) to produce large multilamellar vesicles. The resulting vesicles were passed repeatedly under pressure through 0.2, 0.1 and 0.05 μm pore size polycarbonate membranes, until the average size distribution for the diameter (monitored by dynamic light scattering using a Coulter N4MD (Hialeah, Fla.)) was approximately 100 nm. The mean particle dia...

example 2

Preparation of Anti-E-selectin Fab Conjugate and Insertion into Pre-Formed Liposomes

A. Preparation of the Targeting Conjugate

[0131] An anti-E-selectin Fab fragment was conjugated to PEG-DSPE to form a targeting conjugate as follows. An aqueous solution of 750 mM 2-mercaptoethylamine as a reducing agent was prepared. 10 μl of the mercaptoethylamine was added to 1 ml of 5 mg / ml anti E-selectin Fab fragment in 50 mM sodium acetate and 125 mM NaCl, pH=5.0. The final concentration of reducing agent was 7.5 mM. The solution was incubated at 37° C. for 30 minutes. The excess reducing agent was removed on a 10DG-column (Bio-Rad) equilibrated with 25 mM HEPES / 0.9% saline buffer. The collected fractions were analyzed spectrophotometrically to determine the fractions containing the Fab fragments. These fractions were pooled and diluted 1:50 in phosphate buffered saline to determine the protein concentration.

[0132] The Fab fragments (molecular weight of 3,000 Daltons) were mixed in a 1:1 mo...

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Abstract

Reagents for use in preparing a therapeutic liposome composition sensitized to a target cell are described. The reagents include a liposomal composition composed of pre-formed liposomes having an entrapped therapeutic agent and a plurality of targeting conjugates composed of a lipid, a hydrophilic polymer and a targeting ligand. The therapeutic, target-cell sensitized liposome composition is formed by incubating the liposomal composition with a selected conjugate.

Description

[0001] This application is a continuation of U.S. application Ser. No. 09 / 876,707 filed Jun. 7, 2001, now pending; which is a division of U.S. application Ser. No. 09 / 517,224 filed Mar. 2, 2000, now U.S. Pat. No. 6,316,024; which is a division of U.S. application Ser. No. 09 / 138,480 filed Aug. 21, 1998, now U.S. Pat. No. 6,056,973; which is a continuation-in-part of U.S. application Ser. No. 08 / 949,046 filed Oct. 10, 1997, now U.S. Pat. No. 5,891,468; which claims the benefit of U.S. Provisional Application No. 60 / 028,269 filed Oct. 11, 1996, now abandoned; all of which are incorporated herein by reference in their entirety.FIELD OF THE INVENTION [0002] The present invention relates to a target-cell sensitized therapeutic liposome composition and to a method of preparing the composition. A library for preparation of the composition is also described. BACKGROUND OF THE INVENTION [0003] Liposomes, spherical, self-enclosed vesicles composed of amphipathic lipids, have been widely studi...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K9/127A61K51/12
CPCA61K9/127A61K9/1271A61K9/1272A61K47/48053A61K47/4823A61K47/48238Y10S436/829A61K47/48815A61K47/48823A61K51/1234C07K16/2854C07K2317/55Y10S424/812A61K47/48561A61K47/544A61K47/61A61K47/62A61K47/6849A61K47/6911A61K47/6913
Inventor ALLEN, THERESA M.USTER, PAULMARTIN, FRANCIS J.ZALIPSKY, SAMUEL
Owner ALZA CORP
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