The Liposome Company, Inc.

The University of British Columbia

Tekmira Pharmaceuticals Corporation

Inex Pharmaceuticals Corporation

Acuitas Therapeutics, Inc.

Hana Biosciences, Inc.

Arbutus Biopharma Corporation

The Lipsome Company, Inc.

Alnylam Pharmaceuticals, Inc.

Mayer, Lawrence D.

Bally, Marcel B.

Madden, Thomas D.

Cullis, Pieter R.

Hope, Michael J.

Fountain, Michael W.

Thomas D Madden

Pieter Rutter Cullis

Michael J Hope

Marcel B Bally

Sean C Semple

Andrew S Janoff

Michael W Fountain

Richard S Ginsberg

Hugh P Schieren

Regina L Jablonski

Pieter R Cullis

Jianxin Chen

Steven Michial Ansell

Quet F Ahkong

Lawrence D Mayer

Marco A Ciufolini

Murray S Webb

Kim F Wong

John J Kearns

Anthony G Durning

Barbara Mui

Barbara Low Shoud Mui

John W Holland

Paulo Jia Ching Lin

Srinivasulu Masuna

Muthiah Manoharan

Kallanthottathil G Rajeev

Xinyao Du

Lawrence T Boni

Robert P Lenk

Joel B Portnoff

Peter Scherrer

Norbert Maurer

Patricia M Logan

Robert J Klimchak

Andreas H Sarris

Sandra K Klimuk

James H Goldie

Clive T R Burge

Fernando Cabanillas

Lewis S Choi

Phalgun Joshi

Christopher J Barbosa

Christopher James Barbosa

Tao Chen

Barbara L S Mui

Jung Soo Kim

David Tirrell

Charmaine W Chang

Lana W Barber

Howard J Lim

Peter Cullis

Yuehua He

Joel Portnoff

Fountain Michael W

Huge P Schieren

Barbara Ls Mui

Martin A Maier

Muthusamy Jayaraman

Akin Akinc

Marco A Cuifolini

Ismail Mahmoud Hafez

Masunu Srinivasulu

Improved formulations of lipid nanoparticles are provided. Use of the lipid nanoparticles for delivery of a therapeutic agent and methods for their preparation are also provided.

Lipid nanoparticle formulations

The present invention provides superior compositions and methods for the delivery of therapeutic agents to cells. In particular, these include novel lipids and nucleic acid-lipid particles that provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of specific target proteins at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

Amino lipids and methods for the delivery of nucleic acids

The present invention includes novel liposomes comprising dihydrosphingomyelin. The invention also includes compositions comprising these liposomes and a therapeutic agent, in addition to methods and kits for delivering a therapeutic agent or treating a disease, e.g., a cancer, using these compositions.

Liposomal formulations comprising dihydrosphingomyelin and methods of use thereof

This invention relates to liposomal antineoplastic agents (e.g., camptothecin) compositions and methods of using such compositions for treating neoplasia and for inhibiting angiogenesis. The compositions and methods are useful for modulating the plasma circulation half-life of an active agent.

Liposomal antineoplastic drugs and uses thereof

This invention provides compositions and methods for treating neoplasias in a mammal. In particular, the invention provides liposome-encapsulated vinca alkaloids, e.g., vinorelbine, and methods of treating a mammal using such compositions.

Compositions and methods for treating cancer

This invention relates to improved liposomal camptothecin compositions and methods of manufacturing and using such compositions for treating neoplasia and for inhibiting angiogenesis.

Liposomal camptothecins and uses thereof

The present invention relates generally to the amphiphilic polyelectrolyte, poly(2-ethylacrylic acid) and covalently bonded lipids to generate Lipo-PEAA. These Lipo-PEAA are then used to make pH-sensitive liposomes which become unstable, permeable or fusogenic with certain pH changes. In addition, this invention generally describes methods for delivering therapeutic compounds and drugs to target cells by administering to a host the pH-sensitive liposomes of the present invention.

Polyanionic polymers which enhance fusogenicity

The present invention provides a fusogenic liposome comprising a lipid capable of adopting a non-lamellar phase, yet capable of assuming a bilayer structure in the presence of a bilayer stabilizing component; and a bilayer stabilizing component reversibly associated with the lipid to stabilize the lipid in a bilayer structure. Such fusogenic liposomes are extremely advantageous because the rate at which they become fusogenic can be not only predetermined, but varied as required over a time scale ranging from minutes to days. Control of liposome fusion can be achieved by modulating the chemical stability and/or exchangeability of the bilayer stabilizing component(s). The fusogenic liposomes of the present invention can be used to deliver drugs, peptide, proteins, RNA, DNA or other bioactive molecules to the target cells of interest.

Liposome having an exchangeable component

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.

Methods of preparing low-toxicity drug-lipid complexes

Dehydrated liposomes are prepared by drying liposome preparations under reduced pressure in the presence of one or more protective sugars, e.g., the disaccharides trehalose and sucrose. Preferably, the protective sugars are present at both the inside and outside surfaces of the liposome membranes. Freezing of the liposome preparation prior to dehydration is optional. Alternatively, the protective sugar can be omitted if: (1) the liposomes are of the type which have multiple lipid layers; (2) the dehydration is done without prior freezing; and (3) the dehydration is performed to an end point which results in sufficient water being left in the preparation (e.g., at least 12 moles water/mole lipid) so that the integrity of a substantial portion of the multiple lipid layers is retained upon rehydration. Concentration gradients capable of generating transmembrane potentials can be created across the liposome membranes either before or after dehydration, and the transmembrane potentials resulting from these gradients can be used to load charged materials, e.g., drugs, into the liposomes.

Methods of dehydrating, storing and rehydrating liposomes

Bilayer stabilizing components and their use in forming programmable

Compositions and methods which are useful for the treatment of solid tumors in a host and which are also useful for increasing the therapeutic index of mitoxantrone in a host. The pharmaceutical compositions are liposomal formulations of mitoxantrone in which the liposomes comprise a mixture of cholesterol and a diacylphosphatidylcholine, preferably 1,2-sn-dimyristoyl-phosphatidylcholine.

Liposomal formulations of mitoxantrone

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Vancouver, Canada

Thomas D Madden