The University of British Columbia

The Liposome Company, Inc.

Lewis S Choi

Pieter Rutter Cullis

Marcel B Bally

Helen C Loughrey

Thomas D Madden

Jun Nakano

James P Kutney

Kim F Wong

Murray S Webb

Camille A Boulet

Hiroki Tsukamoto

Michael McHugh

The present invention provides a novel class of polyethylene glycol modified ceramide lipids. The lipids can be used to form liposomes optionally containing various biological agents or drugs, such as anti-cancer agents. In addition, methods of use for the liposomes are provided.

Polyethylene glycol modified ceramide lipids and liposome uses thereof

This invention relates to a method for synthesizing a substantially pure reactive lipid including, for example, N-[4-(p-maleimidophenyl)-butyryl]phosphatidylethanolamine (MPB-PE) and related compositions. The compositions of the present invention are useful as coupling agents and may be incorporated into liposomes and subsequently coupled to proteins, cofactors and a number of other molecules. A preferred coupling method is also disclosed as are protein conjugates.

Method for protein-liposome coupling

The present invention relates to a general method for producing sized protein-liposome conjugates exhibiting enhanced blood circulation times. The present invention also relates to the sized protein-liposome conjugate compositions produced by the method of the present invention. The protein-liposome conjugates of the present invention preferably range in size from about 75 nm to about 200 nm. The liposomes of the invention may have a transmembrane potential across their membranes, and may be dehydrated. In addition, the composition may contain ionizable bioactive agents such as antineplastic agents, and may be used in diagnostic assays.

Preparation of targeted liposome systems of a defined size distribution

The present invention relates to the synthesis of dimer alkaloid compounds, particularly those of the Catharantus (Vinca) family, from an indole unit, such as cantharanthine, and a dihydroindole unit, such as vindoline. A multi-step process is disclosed including the steps of (1) of 1,4-reduction of a first dimeric iminium intermediate to an enamine compound by reaction with a 1,4-dihydropyridine compound; (2) oxidative transformation of the resulting enamine to a second iminium intermediate under controlled aeration; (3) reduction of the second iminium intermediate to form the target dimer alkaloid compounds. The entire process can be conducted in a one-pot operation to obtain the target compounds without isolation of the intermediates.

Process of synthesis of vinblastine and vincristine

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Burnaby, Canada

Lewis S Choi