CROSS-LINKERS AND THEIR USES

1 - 26 . (canceled)

27 . A method of treating cancer cells expressing a folate receptor in a patient in need of treatment comprising administering to the patient a therapeutically effective amount of a cell-binding agent-drug conjugate of formula (II)

wherein:

CB represents a cell-binding agent;

D represents the drug linked to the cell-binding agent by a disulfide, thioether, thioester, peptide, hydrazone, ester, ether, carbamate, or amide bond;

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 are the same or different and are H, linear alkyl having from 1-6 carbon atoms, branched or cyclic alkyl having from 3 to 6 carbon atoms, linear, branched or cyclic alkenyl or alkynyl having from 2 to 6 carbon atoms, a charged substituent selected from anions selected from SO 3 − , X—SO 3 − , OPO 3 2− , X—OPO 3 2− , PO 3 2− , X—PO 3 2− , CO 2 − , and cations selected from a nitrogen containing heterocycle, N + R 11 R 12 R 13 and X—N + R 11 R 12 R 13 , or a phenyl; wherein:

R 11 , R 12 , and R 13 are the same or different and are H, linear alkyl having from 1 to 6 carbon atoms, branched or cyclic alkyl having from 3 to 6 carbon atoms and X represents phenyl or a linear alkyl from 1 to 6 carbon atoms, or branched or cyclic alkyl having from 3 to 6 carbon atoms;

l, m and n are 0 or an integer from 1 to 4;

A is a phenyl or substituted phenyl, wherein the substituent is a linear alkyl having from 1 to 6 carbon atoms, or a branched or cyclic alkyl having from 3 to 6 carbon atoms, or a charged substituent selected from anions selected from SO 3 − , X—SO 3 − , OPO 3 2− , X—OPO 3 2− , PO 3 2− , X—PO 3 2− , CO 2 − , and cations selected from a nitrogen containing heterocycle, N + R 11 R 12 R 13 and X—N + R 11 R 12 R 13 , wherein X has the same definition as above, and wherein g is 0 or 1;

Z is absent, a polyethyleneoxy unit of formula (OCH 2 CH 2 ) p , wherein p is 0 or an integer from 2 to about 1000, or a F1-E1-P-E2-F2 unit in which E1 and E2 are the same or different and are C═O, O, or NR 14 , wherein R 14 is H, a linear alkyl having from 1-6 carbon atoms, a branched or cyclic alkyl having from 3 to 6 carbon atoms, a linear, branched or cyclic alkenyl or alkynyl having from 2 to 6 carbon atoms; P is a peptide unit between 2 and 20 amino acids in length, wherein E1 or E2 can be linked to the peptide through the terminal nitrogen, terminal carbon or through a side chain of one of the amino acids of the peptide; and F1 and F2 are the same or different and are an optional polyethyleneoxy unit of formula (OCH 2 CH 2 ) p , wherein p is 0 or an integer from 2 to about 1000, provided that when Z is not F1-E1-P-E2-F2, at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is a charged substituent or when g is 1, at least one of A, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 is a charged substituent;

Y represents a carbonyl, thioether, amide, disulfide, or hydrazone group; and

q represents an integer from 1 to 20.

28 . The method of claim 27 , wherein the method is for treating ovarian cancer.

29 . The method of claim 28 , wherein one of R 1 , R 2 , R 3 , R 4 , R 9 , and R 10 is a charged substituent selected from SO 3 − , X—SO 3 − , OPO 3 2− , X—OPO 3 2− , N + R 11 R 12 R 13 and X—N + R 11 R 12 R 13 , and the rest are H; l, g and m are each 0; and n is 1.

30 . The method of claim 28 , wherein one of R 1 , R 2 , R 3 , R 4 , R 9 , and R 10 is SO 3 − or X—SO 3 − , the rest are H; l, g and m are each 0; and n is 1.

31 . The method of claim 28 , wherein the cell-binding agent is an antibody or an antibody fragment that binds to a target cell.

32 . The method of claim 31 , wherein the cell-binding agent is a resurfaced antibody, a resurfaced single chain antibody, or a resurfaced antibody fragment thereof.

33 . The method of claim 31 , wherein the cell-binding agent is a monoclonal antibody, a single chain monoclonal antibody, or a monoclonal antibody fragment thereof.

34 . The method of claim 31 , wherein the cell-binding agent is a human antibody, a humanized antibody or a resurfaced antibody, a humanized single chain antibody, or a humanized antibody fragment thereof.

35 . The method of claim 31 , wherein the cell-binding agent is a chimeric antibody, a chimeric antibody fragment, a domain antibody, or a domain antibody fragment thereof.

36 . The method of claim 28 , wherein the conjugate is represented by the following formula:

wherein CB′-NH— represents the cell-binding agent linked to Y; and D′-S—S— represents the cytotoxic drug linked to the cell-binding agent by a disulfide bond.

37 . The method of claim 36 , wherein the cytotoxic agent is a maytansinoid.

38 . The method of claim 36 , wherein the cytotoxic agent is DM4 and the conjugate is represented by the following formula:

39 . The method of claim 38 , wherein the cell-binding agent is an antibody that binds to a folate receptor.

40 . The method of claim 39 , wherein the folate receptor is FOLR1 (folate receptor 1).