Patent ID: 6358490
Filing Date: 2002-03-19
Classification: A61K,B82Y

Abstract:
A method of enhancing active agent localization at a target site in a mammalian recipient, which method comprises:administering to the recipient a first conjugate comprising an antibody or antigen-binding antibody fragment and a biotin, whereupon the first conjugate localizes to the target site; administering to the recipient avidin or streptavidin; and thereupon administering to the recipient a second conjugate comprising biotin, a linker resistant to biotinidase cleavage and an active agent, wherein second conjugate localization at the target site is enhanced as a result of prior localization of the first conjugate and wherein the active agent is an anti-tumor agent or chemotherapeutic drug, and further wherein the linker is selected from the group consisting of: 1) a D-amino acid-containing linker of the formula 2) a linker of the formula 3) a linker of the formula 4) a linker of the formula â€ƒwherein Lâ€² is selected from the group consisting of: a) â€”NHâ€”COâ€”(CH2)nâ€”Oâ€”; b) â€”NHâ€”; d) â€”NHâ€”CSâ€”NHâ€”; and e) â€”NHâ€”COâ€”(CH2)nâ€”NHâ€”; wherein R1 is hydrogen, lower alkyl; lower alkyl substituted with one or more hydrophilic groups, selected from the group consisting of (CH2)mâ€”OH, (CH2)mâ€”OSO3, (CH2)mâ€”SO3, and â€ƒwhere m is 1 or 2; glucuronide-substituted amino acids; R2 is hydrogen; lower alkyl; substituted lower alkyl having one or more substituents selected from the group consisting of hydroxy, sulfate, and phosphonate; or a hydrophilic moiety; R3 is hydrogen; an amine; a lower alkyl; a hydroxy-, sulfate- or phosphonate-substituted lower alkyl; a glucuronide; or a glucuronide-derivatized amino acid; R4 is hydrogen or lower alkyl; Râ€² is hydrogen, â€”(CH2)2â€”OH or a sulfate or phosphonate derivative thereof; or Râ€³ is a bond or â€”(CH2)nâ€”COâ€”NH; and n ranges from 0-5.