| US 7,585,857 B2 | ||
| Cytotoxic agents comprising taxanes and their therapeutic use | ||
| Ravi V. J. Chari, Newton, Mass. (US); and Walter A. Blättler, Brookline, Mass. (US) | ||
| Assigned to Immunogen Inc., Waltham, Mass. (US) | ||
| Filed on Aug. 23, 2007, as Appl. No. 11/844,183. | ||
| Application 11/844183 is a division of application No. 11/331045, filed on Jan. 13, 2006, granted, now 7,276,499. | ||
| Application 11/331045 is a division of application No. 10/684746, filed on Oct. 15, 2003, granted, now 7,008,942. | ||
| Application 10/684746 is a division of application No. 10/207814, filed on Jul. 31, 2002, granted, now 6,706,708. | ||
| Application 10/207814 is a division of application No. 10/059022, filed on Jan. 30, 2002, granted, now 6,436,931. | ||
| Application 10/059022 is a division of application No. 09/933018, filed on Aug. 21, 2001, granted, now 6,372,738. | ||
| Application 09/933018 is a division of application No. 09/717026, filed on Nov. 22, 2000, granted, now 6,340,701. | ||
| Claims priority of provisional application 60/167228, filed on Nov. 24, 1999. | ||
| Prior Publication US 2008/0027130 A1, Jan. 31, 2008 | ||
| Int. Cl. A61K 31/30 (2006.01); A61K 31/337 (2006.01) | ||
| U.S. Cl. 514—232.2 [514/254.11; 514/320; 514/449] | 25 Claims |
1. A method of inducing cell death in selected cell populations comprising contacting target cells or tissue containing target
cells with an effective amount of a cytotoxic agent, wherein the target cells are cancer cells that express a marker that
binds to the cell binding agent and wherein the cytotoxic agent comprises one or more taxanes covalently bonded to a cell
binding agent through a linking group, wherein at least one of said taxanes is a compound represented by formula (I):
 wherein:
R1 and R1′ are the same or different and are H, —F, —NO2, —CN, Cl, —CHF2, —CF3, —NR7R8, or —OR9, wherein R7 and R8 are the same or different and are linear alkyl having 1 to 10 carbon atoms, branched or cyclic alkyl having 3 to 10 carbon
atoms, or simple or substituted phenyl or naphthyl, and R9 is linear alkyl having 1 to 10 carbon atoms, or branched or cyclic alkyl having 3 to 10 carbon atoms;
R1″ is H;
R2 is —(CH2)nSZ, —CO(CH2)nSZ, —(CH2)nCH(CH3)SZ, —CO(CH2)nCH(CH3)SZ, —(CH2)nC(CH3)2SZ, —CO(CH2)nC(CH3)2SZ, —CONR12(CH2)nSZ, —CONR12(CH2)nCH(CH3)SZ, —CONR12(CH2)nC(CH3)2SZ, —CO-morpholino-XSZ, —CO-piperazino-XSZ, —CO-piperidino-XSZ, or —CO—N-methylpiperazino-XSZ,
wherein Z is H or SR, wherein R and R12 are the same or different and are linear alkyl having 1 to 10 carbon atoms, branched or cyclic alkyl having 3 to 10 carbon
atoms, or simple or substituted phenyl, naphthyl or heterocyclic, and R12 in addition can be H, X is linear alkyl having 1-10 carbon atoms or branched alkyl having 3-10 carbon atoms, and n is an integer
of 1 to 10;
R3 is —CH═C(CH3)2;
R4 is —OC(CH3)3 or phenyl;
R5 together with the oxygen atom at the C-7 position forms a linear ether having from 1 to 10 carbon atoms, or a branched or
cyclic ether having from 3 to 10 carbon atoms; and
R6is H.
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