Drug conjugate composition

Abstract

The invention provides a liquid composition and a lyophilized composition comprising a therapeutically effective amount of a conjugate comprising an antibody chemically coupled to a maytansinoid. The invention further provides a method for killing a cell in a human comprising administering to the human either of the compositions such that the antibody binds to the surface of the cell and the cytotoxicity of the maytansinoid is activated, whereby the cell is killed.

What is claimed is: 
     
         1 . A composition comprising (i) a conjugate comprising an antibody chemically coupled to a maytansinoid, (ii) about 2 mM to about 50 mM of a buffering agent selected from the group consisting of a citrate buffer, an acetate buffer, a succinate buffer, and a histidine buffer, (iii) about 50 mM to about 500 mM sodium chloride, (iv) about 0.002% to about 0.1% wt./vol. of a surfactant, and (v) water, wherein the composition has a pH of about 5-6. 
     
     
         2 . The composition of  claim 1 , wherein the composition further comprises sucrose. 
     
     
         3 . The composition of  claim 2 , wherein the concentration of sucrose in the composition is about 0.1% to about 10% of the total volume of the composition. 
     
     
         4 . The composition of  claim 3 , wherein the concentration of sucrose in the composition is about 2% to about 5% of the total volume of the composition. 
     
     
         5 . The composition of  claim 1 , wherein the concentration of sodium chloride in the composition is about 50 mM to about 100 mM. 
     
     
         6 . The composition of  claim 1 , wherein the composition comprises a histidine buffer. 
     
     
         7 . The composition of  claim 6 , wherein the concentration of the histidine buffer is about 10 mM. 
     
     
         8 . The composition of  claim 1 , wherein the concentration of the buffering agent is about 10 mM to about 20 mM. 
     
     
         9 . The composition of  claim 1 , wherein the concentration of the buffering agent is about 5 mM to about 15 mM. 
     
     
         10 . The composition of  claim 9 , wherein the concentration of the buffering agent is about 10 mM. 
     
     
         11 . The composition of  claim 1 , wherein the concentration of the surfactant is about 0.01% wt./vol. of the total volume of the composition. 
     
     
         12 . The composition of  claim 11 , wherein the surfactant is polysorbate 80 or polysorbate 20. 
     
     
         13 . The composition of  claim 1 , wherein the concentration of the conjugate in the composition is about 0.1 mg/mL to about 5 mg/mL. 
     
     
         14 . The composition of  claim 13 , wherein the concentration of the conjugate in the composition is about 5 mg/mL. 
     
     
         15 . The composition of  claim 1 , wherein the pH of the composition is about 5.5. 
     
     
         16 . The composition of  claim 1 , wherein the antibody is a monoclonal antibody. 
     
     
         17 . The composition of  claim 1 , wherein the antibody is a humanized monoclonal antibody. 
     
     
         18 . The composition of  claim 1 , wherein the maytansinoid comprises a thiol group. 
     
     
         19 . The composition of  claim 18 , wherein the maytansinoid is N2′-deacetyl-N2′-(3 -mercapto-1 -oxopropyl)-maytansine (DM1) or N2′-deacetyl-N2′-(4-mercapto-4-methyl-1-oxopentyl)-maytansine (DM4). 
     
     
         20 . The composition of  claim 1 , wherein the antibody is chemically coupled to the maytansinoid via chemical bonds selected from the group consisting of disulfide bonds, acid labile bonds, photolabile bonds, peptidase labile bonds, thioether bonds, and esterase labile bonds. 
     
     
         21 . A packaged composition comprising a sealed container and dispersed therein the composition of  claim 1  and an inert gas overlay.