	US 7,470,429 B2
	Methods and compositions for increasing the target-specific toxicity of a chemotherapy drug
Gary L. Griffiths, Morristown, N.J. (US); and Hans J. Hansen, Slidell, La. (US)
Assigned to Immunomedics, Inc., Morris Plains, N.J. (US)
Filed on Feb. 06, 2002, as Appl. No. 10/66,782.
Application 10/066782 is a division of application No. 09/399221, filed on Sep. 17, 1999, granted, now 6,361,774.
Claims priority of provisional application 60/101039, filed on Sep. 18, 1998.
Prior Publication US 2002/0114808 A1, Aug. 22, 2002
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 39/00 (2006.01)

U.S. Cl. 424—178.1

14 Claims

1. A method for increasing the target-specific toxicity of a chemotherapeutic agent, comprising:

a) pretargeting an enzyme to a mammalian target site, wherein said pretargeting comprises (i) administering a bispecific antibody or binding fragment thereof, wherein one arm of the bispecific antibody is targeted against a target site antigen and a second arm is targeted against a low molecular weight hapten that is conjugated to said enzyme and (ii) administering a low molecular weight hapten that is conjugated to said enzyme; and

b) administering a cytotoxic chemotherapeutic agent known to act at the target site, or a prodrug form thereof which is converted to the chemotherapeutic agent in situ, which chemotherapeutic agent is also detoxified to form an intermediate of lower toxicity using said mammal's ordinary metabolic processes, whereby the detoxified intermediate is reconverted to its more toxic form by the pretargeted enzyme and thus has enhanced cytotoxicity at the target site, wherein said hapten is DTPA or a DTPA chelate.