By Matthew Willett

In the process of plucking Gendaq Ltd.¿s zinc finger DNA-binding protein technology and consolidating a lead position in the zinc finger gene expression regulation space, Sangamo BioSciences Inc. disclosed Monday an agreement with UltiMAb antibody-makers, Medarex Inc.

The pair will share costs and profits from the joint effort to develop and commercialize fully human antibodies using cell lines that overexpress selected G protein-coupled receptors (GPCRs) created with Sangamo¿s zinc-finger DNA-binding protein transcription factor technology.

The deal is the 12th this year for Medarex. Its vice president of business development, Ronald Pepin, said the GPCR area is a hot one for companies looking for therapeutics.

¿GPCRs are important pharmaceutical targets,¿ Pepin told BioWorld Today. ¿The downside to GPCRs is that they¿re kind of a tough target. These are seven-transmembrane receptors, meaning the protein loops in and out of the cell membrane seven times. The problem with some GPCRs is that the part outside the cell that¿s most accessible to antibodies is quite small. . . . but I think our technology is such that if any approach has a way of working, ours will. That said, scientifically, it¿s a challenge.¿

Creating cell lines that overexpress the targeted GPCRs, however, is a challenge Richmond, Calif.-based Sangamo¿s founder, CEO and president, Edward Lanphier, said his company is up to.

¿Our role is to generate the antigen, and the way we¿ll do that is with our zinc finger technology, going into the cell and specifically turning on the GPCR of interest, causing that gene to be overexpressed,¿ Lanphier told BioWorld Today from Europe. ¿The overexpression of the GPCR gene will cause a significant amount of receptors to be expressed on the surface of the cells, on the cell membrane, and Medarex can use that cell or cell membrane to vaccinate the mice.¿

Sangamo¿s Universal Gene Recognition technology engineers zinc finger DNA-binding proteins, proteins that recognize specific genes. These zinc finger proteins can control gene expression, and therefore, cell function. Sangamo has formed 23 collaborations around the technology with pharmaceutical and biotechnology companies.

The upside for Sangamo is simple, Lanphier said: ¿products.¿

¿We¿re not an antibody company, and we won¿t be an antibody company,¿ he said. ¿This leverages work we¿ve done and work we¿re doing, and doing well, in a class of therapeutics that we wouldn¿t independently be able to access. GPCRs are a very hot area. These are validated targets, very significant targets in pharmaceutical product development, and I think the technology is applicable to any clinically relevant GPCR. It¿s a very significant opportunity.¿

Though there¿s no time limit to the partnership, it¿s likely watchers will see a product from the collaboration ready to enter the clinic in 18 to 24 months, Pepin agreed. Medarex is known for its T12 program ¿ a process that moves pharmaceuticals from target to the clinic in about 12 months.

¿Science is always science,¿ Pepin cautioned. ¿It will take time to engineer the zinc finger to overexpress the GPCRs. That should happen, I¿m guessing, in a six- to nine-month time frame. One of the things about Medarex is that we have a track record, especially in serious unmet medical needs, to go from the target to clinical trials in 12 months, our T12 program, and I don¿t think anyone in the industry can do it any quicker than that.¿

Lanphier cited a confidence in that ability as one of the attractions of Princeton, N.J.-based Medarex. He added that the broad applicability of the collaboration was another.

¿We¿re focused more at this point on the breadth of the combination,¿ Lanphier said. ¿We can apply the zinc finger technology to up-regulate any GPCR; it can be applied to any protein in any clinical field of use, from infectious disease to cancer to inflammation, and those are all areas of interest. The platforms combined can apply to any one of those.¿

Sangamo entered an option agreement two weeks ago to purchase all the outstanding stock of London-based Gendaq and to assume all employee stock options. Sangamo would give up 2.25 million shares, or about 10 percent of the company, in the proposed deal that was valued at 39.6 million. (See BioWorld Today, May 31, 2001.)

Sangamo¿s stock (NASDAQ:SGMO) fell 15 cents Monday, closing at $14.87. Medarex¿s shares (NASDAQ:MEDX) fell $2.29, closing at $27.56.

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