Abstract: A cytotoxic agent comprising one or more taxanes linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more taxanes covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more taxanes linked to a cell binding agent. Novel sulfur-containing taxanes.

Abstract: Prodrugs of analogs of the anti-tumor antibiotic CC-1065 having a cleavable protective group such as a piperazino carbamate, a 4-piperidino-piperidino carbamate or a phosphate, in which the protecting group confers enhanced water solubility and stability upon the prodrug, and in which the prodrug also has a moiety, such as a disulfide, that can conjugate to a cell binding reagent such as an antibody. The therapeutic use of such prodrug conjugates is also described; such prodrugs of cytotoxic agents have therapeutic use because they can deliver cytotoxic prodrugs to a specific cell population for enzymatic conversion to cytoxic drugs in a targeted fashion.

Abstract: A cytotoxic agent comprising one or more taxanes linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more taxanes covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more taxanes linked to a cell binding agent. Novel sulfur-containing taxanes.

Abstract: New thiol and disulfide-containing maytansinoids bearing a mono or di-alkyl substitution on the &agr;-carbon atom bearing the sulfur atom are disclosed. Also disclosed are methods for the synthesis of these new maytansinoids and methods for the linkage of these new maytansinoids to cell-binding agents. The maytansinoid-cell-binding agent conjugates are useful as therapeutic agents, which are delivered specifically to target cells and are cytotoxic. These conjugates display vastly improved therapeutic efficacy in animal tumor models compared to the previously described agents.

Abstract: Prodrugs of analogs of the anti-tumor antibiotic CC-1065 having a cleavable protective group such as a piperazino carbamate, a 4-piperidino-piperidino carbamate or a phosphate, in which the protecting group confers enhanced water solubility and stability upon the prodrug, and in which the prodrug also has a moiety, such as a disulfide, that can conjugate to a cell binding reagent such as an antibody. The therapeutic use of such prodrug conjugates is also described; such prodrugs of cytotoxic agents have therapeutic use because they can deliver cytotoxic prodrugs to a specific cell population for enzymatic conversion to cytoxic drugs in a targeted fashion.

Abstract: Prodrugs of analogs of the anti-tumor antibiotic CC-1065 having a cleavable protective group such as a piperazino carbamate, a 4-piperidino-piperidino carbamate or a phosphate, in which the protecting group confers enhanced water solubility and stability upon the prodrug, and in which the prodrug also has a moiety, such as a disulfide, that can conjugate to a cell binding reagent such as an antibody. The therapeutic use of such prodrug conjugates is also described; such prodrugs of cytotoxic agents have therapeutic use because they can deliver cytotoxic prodrugs to a specific cell population for enzymatic conversion to cytoxic drugs in a targeted fashion.

Abstract: A cytotoxic agent comprising one or more taxanes linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more taxanes covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more taxanes linked to a cell binding agent. Novel sulfur-containing taxanes.

Abstract: Cytotoxic agents bearing a polyethylene glycol (PEG) linking group having a terminal active ester, cytotoxic conjugates comprising one or more cytotoxic agents linked to a cell-binding agent via PEG linking groups, and methods for producing both are disclosed. A therapeutic composition comprising a therapeutically-effective amount of one of the cytotoxic conjugates of the present invention, and a method of killing selected cell populations comprising contacting target cells, or tissue containing target cells, with an effective amount of one of the cytotoxic conjugates, are also disclosed.

Abstract: A cytotoxic agent comprising one or more taxanes linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more taxanes covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more taxanes linked to a cell binding agent. Novel sulfur-containing taxanes.

Abstract: Included within the scope of the present invention are potent taxanes containing a linking group. Also included is a cytotoxic agent comprising one or more taxanes linked to a cell binding agent. A therapeutic composition for inducing cell death in selected cell populations comprising: (A) a cytotoxic amount of one or more taxanes covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier, diluent or excipient is also included. A method for inducing cell death in selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more taxanes linked to a cell binding agent is included as well.

Abstract: Cytotoxic agents bearing a polyethylene glycol (PEG) linking group having a terminal active ester, cytotoxic conjugates comprising one or more cytotoxic agents linked to a cell-binding agent via PEG linking groups, and methods for producing both are disclosed. A therapeutic composition comprising a therapeutically-effective amount of one of the cytotoxic conjugates of the present invention, and a method of killing selected cell populations comprising contacting target cells, or tissue containing target cells, with an effective amount of one of the cytotoxic conjugates, are also disclosed.

Abstract: Prodrugs of analogs of the anti-tumor antibiotic CC-1065 having a cleavable protective group such as a piperazino carbamate, a 4-piperidino-piperidino carbamate or a phosphate, in which the protecting group confers enhanced water solubility and stability upon the prodrug, and in which the prodrug also has a moiety, such as a disulfide, that can conjugate to a cell binding reagent such as an antibody. The therapeutic use of such prodrug conjugates is also described; such prodrugs of cytotoxic agents have therapeutic use because they can deliver cytotoxic prodrugs to a specific cell population for enzymatic conversion to cytoxic drugs in a targeted fashion.

Abstract: Improved synthesis of seco(−)CBI (5-hydroxy-3-amino-1-[S]-(chloromethyl)-1,2-dihydro-3H-benz(e)indole): 1

Abstract: A cytotoxic agent comprising one or more modified doxorubicins/daunorubicin linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more modified doxorubicins/daunorubicins covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more modified doxorubicins/daunorubicins linked to a cell binding agent. Novel sulfur-containing modified doxorubicins/daunorubicins.

Abstract: A cytotoxic agent comprising one or more polyethylene glycol-containing taxanes linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more polyethylene glycol-containing taxanes covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more polyethylene glycol-containing taxanes linked to a cell binding agent.

Abstract: Improved synthesis of seco(−)CBI (5-hydroxy-3-amino-1-[S]-(chloromethyl)-1,2-dihydro-3H-benz(e)indole): and improved syntheses therefrom of a wide variety of CC-1065 analogs that comprise a cyclopropabenzidole (CBI) alkylating moiety, and which are collectively DC1 and its derivatives, for the synthesis of cell-targeted therapeutic agents.

Abstract: The present invention discloses a one-step process for the production of cytotoxic conjugates of maytansinoids and cell binding agents. Maytansinoids having a disulfide linker that bears a reactive moiety are linked to cell binding agents, such as antibodies, without prior modification of the cell binding agent. These conjugates are useful as therapeutic agents which are delivered specifically to target cells and are cytotoxic.

Abstract: Improved synthesis of seco(−)CBI (5-hydroxy-3-amino-1-[S]-(chloromethyl)-1,2 -dihydro-3H-benz(e)indole): and improved syntheses therefrom of a wide variety of CC-1065 analogs that comprise a cyclopropabenzidole (CBI) alkylating moiety, and which are collectively DC1 and its derivatives, for the synthesis of cell-targeted therapeutic agents.

Abstract: A cytotoxic agent comprising one or more taxanes linked to a cell binding agent. A therapeutic composition for killing selected cell populations comprising: (A) a cytotoxic amount of one or more taxanes covalently bonded to a cell binding agent through a linking group, and (B) a pharmaceutically acceptable carrier, diluent or excipient. A method for killing selected cell populations comprising contacting target cells or tissue containing target cells with an effective amount of a cytotoxic agent comprising one or more taxanes linked to a cell binding agent. Novel sulfur-containing taxanes.

Abstract: The present invention discloses a one-step process for the production of cytotoxic conjugates of maytansinoids and cell binding agents. Maytansinoids having a disulfide linker that bears a reactive moiety are linked to cell binding agents, such as antibodies, without prior modification of the cell binding agent. These conjugates are useful as therapeutic agents which are delivered specifically to target cells and are cytotoxic.