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 therapeutically effective amount of a conjugate comprising an antibody chemically coupled to a maytansinoid, (ii) about 5-15 mM sodium succinate buffer, (iii) polysorbate 20 that is about 0.002% to about 0.1% of the total volume of the composition, (iv) sucrose that is about 0.1% to about 10% of the total volume of the composition, and (v) water, wherein the composition has a pH of 6 or less. 
     
     
         2 . The composition of  claim 1 , wherein the antibody is selected from the group consisting of huN901, huMy9-6, huB4, huC242, trastuzumab, bivatuzumab, sibrotuzumab, and rituximab. 
     
     
         3 . The composition of  claim 1 , wherein the maytansinoid comprises a thiol group. 
     
     
         4 . The composition of  claim 3 , wherein the maytansinoid is DM1. 
     
     
         5 . (canceled) 
     
     
         6 . The composition of  claim 1 , wherein the concentration of the conjugate in the composition is about 4 mg/mL or higher. 
     
     
         7 . The composition of  claim 6  wherein the concentration of the conjugate in the composition is about 5 mg/mL. 
     
     
         8 - 9 . (canceled) 
     
     
         10 . The composition of  claim 1 , wherein concentration of the sodium succinate buffer in the composition is of about 10 mM. 
     
     
         11 - 13 . (canceled) 
     
     
         14 . The composition of  claim 1 , wherein the concentration of polysorbate 20 in the composition is about 0.01% of the total volume of the composition. 
     
     
         15 - 23 . (canceled) 
     
     
         24 . The composition of  claim 1 , wherein the concentration of sucrose in the composition 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 7% to about 10% wt./vol. of the total volume of the composition. 
     
     
         25 . (canceled) 
     
     
         26 . A packaged composition comprising a sealed container and dispersed therein the composition of  claim 1  and an inert gas overlay. 
     
     
         27 . The packaged composition of  claim 26 , wherein the inert gas is nitrogen or argon. 
     
     
         28 - 33 . (canceled) 
     
     
         34 . The composition of  claim 1 , wherein the antibody binds to a tumor-specific antigen present on the surface of a tumor cell. 
     
     
         35 . The composition of  claim 34 , wherein the antigen is 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. 
     
     
         36 - 87 . (canceled) 
     
     
         88 . The composition of  claim 1 , wherein the composition further comprises glycine. 
     
     
         89 . The composition of  claim 88 , wherein the concentration of glycine in the composition is about 50 mM to about 500 mM. 
     
     
         90 . The composition of  claim 88 , wherein the concentration of glycine in the composition is about 250 mM. 
     
     
         91 . The composition of  claim 90 , wherein the concentration of sucrose in the composition is about 2% to about 5% wt./vol. of the total volume of the composition. 
     
     
         92 . The composition of  claim 88 , wherein the composition is lyophilized.