Polymorphs of an epothilone analog

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

Reexamination Certificate

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C540S456000, C540S462000

Reexamination Certificate

active

06689802

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to crystalline polymorphic forms of a highly potent epothilone analog that is characterized by enhanced properties.
BACKGROUND OF THE INVENTION
Epothilones are macrolide compounds that find utility in the pharmaceutical field. For example, Epothilones A and B having the structures:
may be found to exert microtubule-stabilizing effects similar to paclitaxel (TAXOL®) and hence cytotoxic activity against rapidly proliferating cells, such as, tumor cells or other hyperproliferative cellular disease, see Hofle, G., et al.,
Angew. Chem. Int. Ed. Engl.,
Vol. 35, No.13/14, 1567-1569 (1996); W093/10121 published May 27, 1993; and WO97/19086 published May 29, 1997.
Various epothilone analogs have been synthesized and may be used to treat a variety of cancers and other abnormal proliferative diseases. Such analogs are disclosed in Hofle et al.,
Id.
; Nicolaou, K. C., et al.,
Angew Chem. Int. Ed. Engl.
Vol. 36, No. 19, 2097-2103 (1997); and Su, D.-S., et al.,
Angew Chem. Int. Ed. Engl.,
Vol. 36, No. 19, 2093-2097 (1997).
A particularly advantageous epothilone analog that has been found to have advantageous activity is [1S-[1R*,3R*(E),7R*,10S*,11R*,12R*,16S*]]-7,11-Dihydroxy-8,8,10,12,16-pentamethyl-3-[1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]-4-aza-17-oxabicyclo[14.1.0]heptadecane-5,9-dione. In accordance with the present invention, two crystal forms of the subject epothilone analog are provided. These polymorphs, which have been designated as Forms A and B, respectively, are novel crystal forms and are identified hereinbelow.


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