The Liposome Company, Inc.

Transave Limited

Insmed Incorporated

Biomira USA Inc.

Lawrence T Boni

Brian S Miller

Andrew S Janoff

Vladimir Malinin

Sharma R Minchey

Xingong Li

Mircea C Popescu

Joel B Portnoff

Christine E Swenson

Walter R Perkins

Patrick L Ahl

Lois E Bolcsak

Jin K Lee

Michael M Batenjany

Thomas S Davis

Pieter Rutter Cullis

Thomas D Madden

Paul A Tremblay

Robert P Lenk

Zhili Li

John J Kearns

Robert J Klimchak

Steven J Weiss

Anthony G Durning

Royden M Coe

Richard J Robb

Frank G Pilkiewicz

Fangjun Wu

Kathy A Stewart

Laura Edgerly-Pflug

Stella Gevantmakher

Royden Coe

Joel Portnoff

Brian Miller

Provided are lipid antiinfective formulations substantially free of anionic lipids with a lipid to antiinfective ratio is about 1:1 to about 4:1, and a mean average diameter of less than about 1 &#x3bc;m. Also provided is a method of preparing a lipid antiinfective formulation comprising an infusion process. Also provided are lipid antiinfective formulations wherein the lipid to drug ratio is about 1:1 or less, about 0.75:1 or less, or about 0.50:1 or less prepared by an in line fusion process. The present invention also relates to a method of treating a patient with a pulmonary infection comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention. The present invention also relates to a method of treating a patient for cystic fibrosis comprising administering to the patient a therapeutically effective amount of a lipid antiinfective formulation of the present invention.

Sustained release of antiinfectives

One aspect of the disclosure relates to a new form of lipid-complexed active platinum compound, which allows for high concentrations of platinum compound in the composition. For example, the concentration of cisplatin in the composition is higher at room temperature, e.g., about greater than 1.2 mg/mL, compared to 1 mg/mL in aqueous solution. In one embodiment, the present invention is directed to a composition comprising a lipid-complexed active platinum compound, wherein the complex has a lipid to drug (L/D) ratio of less than about 1 by weight, e.g. about 0.10 to 1, wherein the lipid-complexed active platinum compound comprises at least one lipid and at least one active platinum compound. In other embodiments, wherein lipid-complexed active platinum compound has an average volume-weighted diameter of about 0.5 to about 20 microns. In still other embodiments, the composition further comprises a liposome. The liposome may comprise at least one lipid, and may further comprise at least one active platinum compound. The disclosure also relates to a pharmaceutical formulation comprising a lipid complexed active platinum compound and a pharmaceutically acceptable carrier or diluent. The pharmaceutical formulation may be formulated for inhalation or injection.

Platinum aggregates and process for producing the same

Provided is a method of preparing lipid based drug formulations with low lipid/drug ratios using coacervation techniques. Also provided are methods of delivering such lipid based drug formulations at high delivery rates, and methods of treating patients with pulmonary diseases comprising administering such lipid based drug formulations.

High delivery rates for lipid based drug formulations, and methods of treatment thereof

Provided, among other things, is a method of treating or ameliorating pulmonary infection in a cystic fibrosis patient comprising pulmonary administration of an effective amount of a liposomal/complexed antiinfective to the patient, wherein the (i) administrated amount is 50% or less of the comparative free drug amount, or (ii) the dosing is once a day or less, or (iii) both.

Disclosed are methods of treating cancers by inhalation of stable platinum-containing formulations.

Treatment of cancers by inhalation of stable platinum-containing formulations

A method for producing multilamellar coalescence vesicles (MLCVs) containing increased amounts of biologically active compound is disclosed. The method involves hydrating at least one powdered lipid in an aqueous buffer at a temperature above the phase transition temperature of the highest melting lipid to form multilamellar vesicles, reducing the size of the multilamellar vesicles to about 20-400 nm to produce small unilamellar vesicles (SUVs) or large unilamellar vesicles (LUVs) or a mixture thereof; and incubating the SUVs, LUVs or mixture thereof with a biologically active compound in an aqueous solution under sufficient conditions to form MLCVs containing the biologically active compound without the use of an organic solvent, a freeze-thawing step or a dehydration step. MLCVs produced by this method contain increased amounts of biologically active compound over prior art liposomes produced with an organic solvent, a freeze-thawing step or a dehydration step and fewer vesicles are substantially free of biologically active compound

Multilamellar coalescence vesicles (MLCV) containing biologically active compounds

Membrane-proteoliposome structures (MPs) are useful in preparing patient-specific vaccines against specific white blood cell (WBC) malignancies. The inventive MPs typically contain a membrane component derived from a specific WBC. Other useful components include immunostimulators and exogenous lipids. The resulting vaccines are both patient- and malignancy-specific.

Patient-specific white blood cell malignancy vaccine from membrane-proteoliposomes

This invention provides a composition containing a sized liposome comprising a lipid and an inducer; the sized liposome has a diameter of at most about 1 micron and the inducer is present in an amount effective to induce interdigitation-fusion of the sized liposome. Also provided herein are interdigitation-fusion liposomes and gels, and methods of making the same.

Pharmaceutical compositions containing interdigitation-fusion liposomes

This invention provides a composition containing a sized liposome comprising a lipid and an induce; the sized liposome has a diameter of at most about 1 micoron and the induces is present in an amount effective to induce interdigitation-fusion of the sized liposome. Also provided herein are interdigitation-fusion liposomes and gels, and methods of making the same.

Methods of preparing interdigitation-fusion liposomes and gels which

Provided herein are liposomal taxane formulations where the liposomal lipid is a phosphatidylcholine; these formulations are useful for treating animals afflicted with cancers.

Taxane-containing phosphatidylcholine liposomes

Methods and compositions are described for nonliposomal lipid complexes in association with toxic hydrophobic drugs such as the polyene antibiotic amphotericin B. Lipid compositions are preferably a combination of the phospholipids dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylglycerol (DMPG) in about a 7:3 mole ratio. The lipid complexes contain a bioactive agent, and may be made by a number of procedures, at high drug:lipid ratios. These compositions of high drug:lipid complexes (HDLCs) may be administered to mammals such as humans for the treatment of infections, with substantially equivalent or greater efficacy and reduced drug toxicities as compared to the drugs in their free form. Also disclosed is a novel liposome-loading procedure, which may also be used in the formation of the HDLCs.

Low toxicity drug-lipid systems

This invention provides a process for the production of liposomes by combining an organic phase and an aqueous at a volume ratio of less than 3:1; the process can be conducted under conditions which obtain a single-modal population distribution of liposomes encompassing a pre-selected mean particle size. A novel intermediate product obtained during the process, which can itself be used for the topical delivery of a bioactive agent, is also provided.

Method of producing liposomes

High ratio active agent:lipid complexes, their preparation and use are disclosed. Particular reference is made to cephalosporin:lipid complex and iodinated contrast agent:lipid complex. Use of high ratio cephalosporin:lipid complex in bacterial prophylaxis, and particularly bacteremia prophylaxis, including a method of preventing bacterial infection in an animal over an extended period comprising the step of administering to said animal a high ratio cephalosporin:lipid complex is further disclosed as is the use of high ratio iodinated contrast agent:lipid complex in X-ray applications.

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Monmouth Junction, NJ, United States of America

Lawrence T Boni