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Targeted Drugs

Contractors score on a new class of cancer therapeutics

by Rick Mullin
May 16, 2005 | A version of this story appeared in Volume 83, Issue 20

Dow Chemical's MeO-DOTA chelating agent complexes a radioactive metal while linking to a monoclonal antibody.
Dow Chemical's MeO-DOTA chelating agent complexes a radioactive metal while linking to a monoclonal antibody.


The push to develop cancer therapies that link cell-killing agents to cell-targeting monoclonal antibodies is creating work for contract manufacturing and service companies.

Last week, Dowpharma, the pharmaceutical services division of Dow Chemical, announced an agreement with Cytogen under which the drug company will use Dow's MeO-DOTA bifunctional chelant technology to radiolabel its prostate-specific membrane antigen (PSMA) antibody, creating a prostate cancer drug.

Meanwhile, Albany Molecular Research was awarded a contract by Seattle Genetics for manufacturing of the linking system employed by Seattle Genetics in SGN-35, an antibody-drug conjugate that combines a monoclonal antibody with a cytotoxic compound.

Cytogen opted to use the Dow technology after the open-chain-linking process employed in its Prostascint (capromab pendetide) molecular imaging agent proved insufficiently stable for binding therapeutic radionuclides, according to Michael D. Becker, Cytogen's CEO. Because of its cyclic structure, Becker says, MeO-DOTA holds the radionuclide more tightly than can an open-chain link.

Seattle Genetics has transferred the process for producing its enzyme-cleavable linking technology to Albany Molecular so the contract chemistry firm can manufacture the compound under current Good Manufacturing Practice conditions. Seattle Genetics plans to begin clinical trials on SGN-35 early next year as a treatment for Hodgkin's disease, according to CEO Clay Siegall.

There are currently only two radiolabeled drugs on the market--Bexxar from Corixa and GlaxoSmithKline, and Zevalin from Biogen Idec. Both of these target non-Hodgkin's lymphoma, Becker notes, while PSMA is a solid cell cancer therapy. Wyeth's Mylotarg, a treatment for acute myeloid leukemia, is the only antibody-drug conjugate approved by FDA.


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