West Coast Editor

The drug industry may seldom advance by leaps and bounds, but Therapeutic Human Polyclonals Inc. is pushing things along with a significant hop by creating the first transgenic rabbits to make human antibodies.

Roland Buelow, chief scientific officer and co-founder of the Mountain View, Calif.-based company, will offer results of proof-of-concept studies using polyclonal antibodies from the rabbits at a scientific conference this week on transgenic animals in Tahoe City, Calif.

Polyclonals, THP noted, can bind and eliminate many targets linked with complex diseases, binding multiple antigens and saturating a target, so they stay active even if the antigen mutates, which gives them a strong advantage over monotherapy.

Although transgenic mice have allowed for impressive research through the likes of Medarex Inc., of Princeton, N.J., and Fremont, Calif.-based Abgenix Inc., THP said rabbits are preferred for commercial-scale therapeutic antibodies, and polyclonals - which mice are too small to make - could "revolutionize" the drug world.

"Our rabbits can be used for monoclonals, as well, but it's not the focus of the company," Wim van Schooten, CEO of THP, told BioWorld Today. "They are more of a byproduct than anything else."

Late last month, polyclonals made news when Kirin Brewery Co. Ltd., of Tokyo, paid $45 million in cash for Sioux Falls, S.D.-based Hematech LLC's technology that makes bovine-derived human polyclonal antibodies. (See BioWorld Today, July 27, 2005.)

In animal polyclonals, "it's Hematech and us," Van Schooten said. "We believe rabbits have very distinct advantages over cows. They've been used for many decades to make polyclonals for human use, and there's no approved drugs from cows on the market."

Polyclonal antibodies have been used in the clinic for more than a century. Those derived from horses and sheep were introduced in the 1890s for pneumococcal pneumonia, meningococcal meningitis, scarlet fever, diphtheria and measles. They have not caught on widely as "serum therapy," though, because of animal-derived proteins' immunogenicity problems in humans - the same challenge monoclonal antibodies faced at first.

One strong example of a current rabbit polyclonal is the anti-thymocyte globulin Thymoglobulin to prevent renal transplant rejection from Fremont, Calif.-based SangStat Medical Corp., which was bought two years ago for $585 million by Genzyme Corp., of Cambridge, Mass. (See BioWorld Today, Aug. 5, 2003.)

THP had a deal with SangStat that Genzyme inherited.

"Thymoglobulin dominates that market because it's so powerful and so potent, but it's a rabbit antibody so it can't go into other diseases than organ transplantation," Van Schooten said, adding that work is under way to humanize the compound so that it might be used in other disorders, including autoimmune diseases and cancer.

"We are doing it and they have access to our animals to make the product," he said.

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