UniversitÈ Laval

Bcm Developpement, Inc.

Bcm Developement Inc.

Michel Page

Cyrille Bicamumpaka

Marie-Claude Helie

Maurice Boissinot

Martin Gagne

Mario Harvey

Denis Thibeault

Marie-Josee Perron

Renee Paradis

The present invention relates to a method of obtaining different biologically pure cultures of bacteria isolated from different species of Taxus such as Taxus canadensis. T. brevifolia, T. baccata, T. cuspidata, and T. hunnewelliana, wherein the bacteria produce in vitro taxanes and paclitaxel, and wherein the bacteria are of the genus Sphingomonas, Bacillus, Pantoea or Curtobacterium. Also, the present invention relates to a method of a bacterial mass production of at least one taxane or paclitaxel. There is also disclosed a novel bacterial taxane. The present invention also relates to the use of different biologically pure cultures of bacteria isolated from different species of Taxus, wherein the bacteria are able to biotransform pro-taxanes. There is also provided a process for improving taxanes and paclitaxel production of taxanes and paclitaxel producing bacteria which include culturing bacteria in the presence of a mutagenic agent for a period a time sufficient to allow mutagenesis. There is disclosed two new mutated bacteria which have an increased yield of pro-taxane biotransformation.

Bacterial mass production of taxanes and paclitaxel

Taxanes are purified by chromatographic separation using a phenylalkyl chromatographic resin, wherein the alkyl portion of the phenylalkyl is a C.sub.4 -C.sub.10 moiety. Taxanes such as paclitaxel, 10-deacetyltaxol, 7-epi-taxol, cephalomannine, baccatin III, baccatin V, 7-epi-DAB, 10-deactylbaccatin III ('DAB') and 9-dihydro-13-acetylbaccatin III ('DHB') and others may be purified. In accordance with the invention, taxanes are separated from each other and from other impurities common to crude taxane samples.

Method for the purification of taxanes

The invention relates to new paclitaxel derivatives showing an increased solubility in water. More particularly, the invention relates to glutarylpaclitaxel, glutarylpaclitaxel 6-aminohexanol glucuronide and to different amino acid derivatives of the glutarylpaclitaxel, all of which possess the cytotoxicity activity of the parent compound, paclitaxel. Also disclosed are fluorescent derivatives of paclitaxel for determining a concentration of paclitaxel in a medium or for detecting apoptotic cancer cells.

Water-soluble derivatives of paclitaxel, method for producing same and

The present invention relates to antitumor compounds of the formula I: ##STR1## wherein M is selected from the group consisting of an hydrogen atom, a peptide residue, and a protein residue linked to the carbon atom via the amino residue of .epsilon.-lysine present therein which can be an antibody used to target the anti-tumor agent to the malignant cells, and R can be an antitumor agent such as daunorubicin, doxorubicin, or an epirublicin derivative.

Coupling of an anti-tumor to an antibody using glutaraldehyde

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Michel Page