| US 7,585,491 B2 | ||
| Immunoconjugates with an intracellularly-cleavable linkage | ||
| Serengulam V. Govindan, Summit, N.J. (US) | ||
| Assigned to Immunomedics, Inc., Morris Plains, N.J. (US) | ||
| Filed on Dec. 15, 2003, as Appl. No. 10/734,589. | ||
| Claims priority of provisional application 60/433017, filed on Dec. 13, 2002. | ||
| Prior Publication US 2004/0185053 A1, Sep. 23, 2004 | ||
| Int. Cl. C12P 21/08 (2006.01) | ||
| U.S. Cl. 424—1.49 [530/391.1; 530/391.7; 530/391.9] | 40 Claims |
| 1. An immunoconjugate comprising:
(a) an antibody;
(b) a chemotherapeutic moiety; and
(c) a linker comprising (i) a thiol-reactive functional group that binds to a thiol group on the antibody, and (ii) a water-solubilizing
moiety selected from the group consisting of ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA),
triethylenetetraminehexaacetic acid (TTHA), benzyl-DTPA, 1,4,7,10-tetraazacyclododecane-,N,N′,N″,N′″-tetraacetic acid (DOTA),
benzyl-DOTA, 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA), benzyl-NOTA, 1,4,8,11-tetraazacyclotetradecane-1,4,8,11-tetraacetic
acid (TETA) and N,N′-dialkyl substituted piperazine,
wherein the chemotherapeutic moiety is attached to the linker via an intracellularly-cleavable moiety that is cleavable by
intracellular esterases and comprises an ester formed from the α-carboxylic acid of an amino acid, and said thiol-reactive
functional group is a maleimide or vinylsulfone which links to thiol groups of said antibody.
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