Genzyme Transgenics Corp. announced that it has been able toobtain high levels of recombinant human antithrombin III (AT-III) from the offspring of its transgenic goats. Up to 7 grams ofthe drug per liter of goat's milk have been expressed by theanimals, the company said.
During its initial public offering last July, the companyannounced that it had been able to extract 1 gram of AT-IIIper liter of mouse milk.
The Framingham, Mass., company (NASDAQ:GZTC), a majority-owned subsidiary of Genzyme Corp., is currently preparing foran investigational new drug submission to FDA. In pre-INDdiscussions with the agency, Genzyme Transgenics is explainingto FDA its plans to establish a production herd of AT-III-expressing goats from the founding male, said James Geraghty,the company's president and chief executive officer. "Thefounding male is equivalent to a master cell bank," Geraghtytold BioWorld, so plans to derive AT-III through futuregenerations of goats must past muster with FDA.
AT-III, a protease inhibitor, is currently derived from humanplasma. It is used to treat hereditary AT-III deficiency, whichresults in the proliferation of blood clots. Approximately one inevery 5,000 to 10,000 people suffer from this disorder,company spokeswoman Kathleen Rinehart said. People alsoacquire a deficiency of AT-III from illnesses such as liverdisease and septicemia and from surgical procedures, such aship and knee replacement, she added. Plasma-derived AT-IIIis approved for treatment of this deficiency in Europe andJapan.
The company predicted that its recombinant AT-III fromtransgenic animals will be cheaper than plasma-derived AT-III, and it is hoping to establish an improved efficacy andsafety profile.
Genzyme Transgenics currently has five AT-III-producinggoats. One the males sired three of the AT-III-expressing goats,Geraghty said, and will be the "founder" of the production herd.
He added that, to the best of his knowledge, GenzymeTransgenics is the only company that has successfully bredtransgenic goats. In addition to the AT-III goats, the companyalso has successfully bred a herd of transgenic goats, now in itsthird generation, that produce a long-acting tissue plasminogenactivator (LATPA). In December, the company began injectinggoats with a human gene that will cause them to produce amonoclonal antibody to be used as a treatment for stomachcancer. The company has found expression in mice of the MAbat 4 g/L, Geraghty said.
Transgenic male goats are bred with non-transgenic females toavoid confusion that might result from not knowing whichtransgene was causing expression of drugs, Geraghty added, sothe company could theoretically breed an infinite number ofAT-III-expressing goats from its founding male. GenzymeTransgenics has estimated a worldwide market potential forAT-III of $300 million per year.
-- Karl A. Thiel Associate Editor
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