The University of British Columbia

University of Alberta

Alza Corporation

Sequus Pharmaceuticals, Inc.

Cornell Research Foundation Inc.

Linear Technology Corporation

Liposome Technology, Inc.

G. Gaslini Children's Hospital

Fondazione Centro San Raffaele Del Monte

Sequus Pharmaceuuticals, Inc.

San Raffaele S.r.l.

Theresa M Allen

Raymond John Andersen

Francis J Martin

Samuel Zalipsky

Edward Piers

Paul S Uster

John Coleman

Dilip De Silva

Fangming Kong

Debra Wallace

David L Burgoyne

Michel Roberge

Shi Kun Huang

Alberto Gabizon

Angelo Corti

Jon C Clardy

E Dilip De Silva

Michael Roberge

Darrin D Stuart

Julie S Racok

Linda S Brinen

Mirco Ponzoni

This invention relates to derivatives of hemiasterlin or Geodiamolide G having anti-mitotic activities and useful in treating cancer. These derivatives are represented by general formula I, wherein Y, n, R, R, R, R, R, R, R, R, R, and Rare as defined in the specification.

Biologically active peptides and compositions, their use

The present invention relates to targeted delivery systems for delivering therapeutic agents to tumor. The invention further relates to methods of delivering a therapeutic agent to a tumor for the prevention and treatment of cancer by killing tumor cells and tumor-associated endothelial cells. In particular, the present invention provides a tumor-targeted drug delivery system comprising a NGR-containing molecule linked to a delivery vehicle encapsulating a therapeutic agent, preferably a drug, such as a cytotoxic agent or a chemotherapeutic agent. Specifically, the delivery systems of the present invention are capable of delivering an increased amount of therapeutic agent to a tumor as compared to other delivery systems. In particular, the delivery systems of the present invention are capable of accumulating a higher amount of therapeutic agent in a tumor, or in the vicinity of a tumor cell or tumor-supporting cell, resulting in exposure of the tumor cell and tumor-associated endothelial cell to therapeutic levels of the agent for a longer period of time as compared to other delivery systems. The present invention also describes pharmaceutical compositions comprising the delivery systems of the present invention. The present invention further relates to a tumor treatment comprising an increased amount of therapeutic agent delivered by the system of the present invention as compared to other delivery systems. The delivery systems and pharmaceutical compositions can be administered to a subject, preferably a human, alone or in combination, sequentially or simultaneously, with other prophylactic or therapeutic agents and/or anti-cancer treatments.

Tumor-targeted drug delivery systems and uses thereof

Derivatives of hemiasterlin or Geodiamolide G having anti-mitotic activities and useful in treating cancer. These derivatives are represented by formula I wherein Y, n, R, R, R, R, R, R, R, R, and Rare as defined in the specification.

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.

Therapeutic liposome composition and method of preparation

A liposomal composition and a method of using the same for achieving intracellular delivery of a liposome-entrapped agent is described. The liposomes are composed of a pH sensitive lipid and include a targeting ligand to direct the liposomes to a target cell. The liposomes also include a stabilizing component, such a polymer-derivatized lipid, where the polymer is attached to the lipid by a releasable linkage. Administration of the liposomes results in cellular internalization and destabilization of the liposome for intracellular delivery of the entrapped agent.

Liposome composition for improved intracellular delivery of a therapeutic agent

This invention relates to derivatives of hemiasterlin or Geodiamolide G having anti-mitotic activities and useful in treating cancer. These derivatives are represented by general formula I,

A liposome composition for administration of a polynucleotide and a method of preparing the composition are described. The liposomes in the suspension are composed predominantly of liposomes having a bilayer membrane formed of cationic vesicle-forming lipids and neutral vesicle forming lipids. The polynucleotide is entrapped in the central core of the liposomes and is localized predominantly on the inner surface of the core.

Liposome-entrapped polynucleotide composition and method

Contignasterol compounds and pharmaceutical compositions comprising the

A method of treating a subject having a disorder characterized by a neoplasm of B-lymphocyte or T-lymphocyte lineage cells is described. The method includes administering a suspension of liposomes having a surface coating of polyethylene glycol chains. Attached to the distal ends of the chains are antibodies or antibody fragments effective to bind to an antigen specific to the affected cells. In one embodiment, anti-CD19 antibodies are attached to the liposome-bound chains, for treatment of multiple myeloma.

Liposomes for treatment of B-cell and T-cell disorders

A method of administering an anti-tumor compound to a subject is disclosed. The method includes administering to a subject liposomes having sizes predominantly in the range 0.05 to 0.12 microns, and containing an anti-tumor compound in liposome-entrapped form, a surface coating of polyethylene glycol chains, at a surface concentration thereof sufficient to extend the blood circulation time of the liposomes severalfold over that of liposomes in the absence of such coating, and surface-attached antibody molecules effective to bind specifically to tumor-associated antigens present at the tumor site. One liposome composition includes doxorubicin in entrapped form, and, on the liposome surface, a monoclonal antibody against highly proliferating cells in a lung squamous cell carcinoma.

Solid-tumor treatment method

The invention presents compounds useful for the prevention of inflammatory or allergic reaction or the treatment of cardiovascular or haemodynamic disorders having the formula: ##STR1## where R= ##STR2## where R= ##STR3## or pharmaceutically acceptable acids or salts thereof.

Contignasterol, and related 3-alpha hydroxy-6-alpha hydroxy-7-beta

5-Methylimidazo[4,5-e]-1,2-thiazin-4(5-H)-one, having the structure ##STR1## a cytotoxic metabolite of the marine sponge Neamphius huxleyi, has been isolated from the sponge by extraction and chromatography.

Biologically active thiazine

A composition of liposomes which contain an entrapped pharmaceutical agent and are characterized by (a) liposome sizes predominantly between about 0.07 and 0.5 microns; (b) at least about 50 mole percent of a membrane-rigidifying lipid, such as sphingomyelin or neutral phospholipids with predominantly saturated acyl chains; and (c) between about 5-20 mole percent of a glycolipid selected from the group consisting of ganglioside GM.sub.1, saturated phosphatidylinositol, and monogalactosyl stearate. The liposomes show high blood/RES tissue distribution ratios, and are effective for drug administration to tumors via intravenous drug delivery.

Growing community of inventors

Edmonton, Canada

Theresa M Allen