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.

1 . A composition comprising (i) a conjugate comprising a humanized monoclonal antibody chemically coupled to N 2′ -deacetyl-N 2′ -(3-mercapto-1-oxopropyl)-maytansine (DM1) via a linker molecule selected from the group consisting of N-succinimidyl 4-(2-pyridyldithio)pentanoate (SPP) and N-succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC), (ii) about 10 mM to about 20 mM of a buffering agent selected from the group consisting of an acetate buffer, a succinate buffer, and a histidine buffer, (iii) about 0.1% to about 3% wt./vol., about 2% to about 5% wt./vol., or about 4% to about 6% wt./vol. sucrose, (iv) about 50 mM to about 500 mM glycine or mannitol, (v) about 0.002% to about 0.1% wt./vol. of a surfactant, and (vi) water, wherein the composition has a pH of about 5-6. 
     
     
         2 . The composition of  claim 1 , wherein the concentration of sucrose is about 0.1% to about 1% wt./vol. of the total volume of the composition. 
     
     
         3 . The composition of  claim 1 , wherein the composition comprises glycine. 
     
     
         4 . The composition of  claim 3 , wherein the concentration of glycine is about 250 mM. 
     
     
         5 . The composition of  claim 1 , wherein the composition comprises mannitol. 
     
     
         6 . The composition of  claim 5 , wherein the concentration of mannitol is about 250 mM. 
     
     
         7 . The composition of  claim 1 , wherein the surfactant is polysorbate 80 or polysorbate 20. 
     
     
         8 . The composition of  claim 1 , wherein the composition comprises a succinate buffer. 
     
     
         9 . The composition of  claim 1 , wherein the concentration of the buffering agent is about 10 mM. 
     
     
         10 . The composition of  claim 1 , wherein the concentration of the conjugate is about 0.1 mg/ml to about 5 mg/ml. 
     
     
         11 . The composition of  claim 1 , wherein the concentration of the conjugate is about 1 mg/mL or about 5 mg/mL. 
     
     
         12 . The composition of  claim 1 , wherein the pH of the composition is about 5.5. 
     
     
         13 . The composition of  claim 1 , wherein the humanized monoclonal antibody is huN901. 
     
     
         14 . The composition of  claim 1 , wherein the antibody binds to an antigen selected from the group consisting of NCAM/CD56, CD33, CD19, GD3, CanAg, PSMA, alpha-folate receptor, Her2/neu, CD44v6, fetoacinar pancreatic (FAP) antigen, Cripto-1, CA6, CD20, CA55.1, MN/CA IX, and chondroitin sulfate proteoglycan. 
     
     
         15 . A packaged composition comprising a sealed container and dispersed therein the composition of  claim 1  and an inert gas overlay. 
     
     
         16 . A lyophilized composition of the composition of  claim 1 . 
     
     
         17 . A packaged composition comprising a sealed container and dispersed therein the composition of  claim 16  and an inert gas overlay. 
     
     
         18 . The composition of  claim 1 , wherein the concentration of sucrose is about 0.5% wt./vol. of the total volume of the composition, or about 5% wt./vol. of the total volume of the composition. 
     
     
         19 . The composition of  claim 1 , wherein the concentration of sucrose is about 0.1% to about 3% wt./vol. of the total volume of the composition, or about 2% to about 5% wt./vol. of the total volume of the composition, or about 4% to about 6% wt./vol. of the total volume of the composition. 
     
     
         20 . The composition of  claim 1 , wherein the buffering agent is an acetate buffer or a histidine buffer. cm  21 . A composition comprising (i) about 0.1 mg/ml to about 5 mg/ml huN901 chemically coupled to N 2′ -deacetyl-N 2′ -(3-mercapto-1-oxopropyl)-maytansine (DM1), (ii) 10 mM sodium citrate, (iii) 0.5% wt./vol. sucrose, (iv) 250 mM glycine, (v) 0.01% wt./vol. polysorbate 20, and (vi) water, wherein the composition has a pH of 5.5.