CYTOTOXIC CD44 ANTIBODY IMMUNOCONJUGATES

• Main Authors: KARL-HEINZ HEIDER, ERIK PATZELT, GUENTHER ADOLF, MARLIES SPROLL
• Format: Patent
• Language: English
• Published: 30.04.2004
• Edition: 7
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present invention relates to novel conjugates of antibodies with cytotoxic compounds, pharmaceutical compositions containing such conjugates, and their use in cancer therapy. In particular, the present invention relates to conjugates of antibodies which are specific for CD44 with maytansinods, preferably with N<2'>-deacetyl-N<2'>-(3-mercapto-1-oxopropyl)-maytansine. In a particularly preferred embodiment, the antibody/maytansinoid conjugate may be prepared from a maytansinoid of formula wherein R1 represents H or SR4, wherein R4 represents methyl, ethyl, linear alkyl, branched alkyl, cyclic alkyl, simple or substituted aryl, or heterocyclic; R2 represents Cl or H; R3 represents H or CH3; and m represents 1,2, or 3. Preferably, R1 is H or CH3, R2 is Cl, R3 is CH3, and m=2. The compound with R1=H, R2=Cl, R3=CH3, and m=2 is designated DM1 in the literature.