Immunomedics Inc announced the issuance of Israeli patent 114830, with an expiration date of August 3, 2015. This patent covers immunoconjugates that are polyspecific, or binding more than one target, so that both the multidrug resistance gene product and antigens associated with cancer or infectious agents can be treated.

The pharmaceutical compositions patented also include drugs, isotopes, and immunomodulators that can be targeted to the cancer cells or infectious agents for a selective therapy.

Drug resistance is a major obstacle to the successful treatment of many cancers and infections, such as bacteria and parasites. One important mechanism responsible for this resistance that is developed against a variety of chemotherapy agents is related to the increased expression of certain proteins of the membrane of the resistant cells, such as the P-glycoprotein.

It is generally believed that P-glycoprotein and related molecules are responsible for cancer cells or microorganisms pumping out the cytotoxic drugs that constitute many of the conventional chemotherapy agents, giving rise to multidrug resistance, or MDR, which results in a cross-resistance to many drugs affected by MDR.

"By constructing polyspecific immunoconjugates, or antibodies, which target both the MDR protein and to cancer cells or infectious agents, selective blocking of MDR may be achieved," commented the inventor and Immunomedics' chairman, Dr. David M. Goldenberg. "This method may allow the cancer cells to be susceptible to the common drugs affected by MDR, while the normal cells having MDR are unaffected and thus protected from the drugs," Dr. Goldenberg commented further.

The Immunomedics invention involves the use of at least two antibodies fused together to result in a bispecific molecule to target both the cancer cells (or infectious organisms) and the P-glycoprotein of MDR. "By constructing specific targeting vehicles that bind both the protein drug-pumps and cancer cells, selective delivery of a therapeutic or diagnostic agent to the P-glycoprotein-expressing cancer cells could be possible, and is certainly extendible to many different cancers, infectious organisms, and classes of drugs," Dr. Goldenberg remarked.

He explained further: "The invention also permits the attachment of various diagnostic labels to the bispecific antibodies, so that tumors expressing P-glycoprotein potentially could be identified prior to high-dose chemotherapy with drugs that are affected by MDR, thus perhaps allowing other therapeutic interventions, including the polyspecific immunoconjugates of this invention, to be applied."