Alexion Pharmaceuticals Inc. signed an agreement with abiotechnology research consortium to become the worldwideexclusive licensee of porcine embryonic stem cells and relatedtechnologies for use in the production of transgenic animalswhose organs and cells can be used for human transplantation.

To date, embryonic stem cells have only been isolated in themouse system. A group of scientists funded by theBiotechnology Research and Development Corp. (BRDC) isolatedembryonic stem cells from the pig. BRDC, which has exclusiverights to technology developed under its sponsorship, in turnlicensed the stem cells to Alexion.

BRDC has a patent pending for the porcine embryonic stemcells. The members of BRDC, formed in the mid-1980s, areAmerican Cyanamid Co., Amoco Technology Co., Hewlett-Packard Co., Mallinckrodt Inc., the Dow Chemical Co., ImceraGroup Inc., Agricultural Research and Development Corp. andAlexion.

Since embryonic stem cells are the cells from which all othercells in the body are derived, Alexion's president and chiefexecutive officer, Leonard Bell, explained that "if onegenetically modifies the stem cell, one can modify the entireanimal."

Alexion is focusing on developing a gene-targeting sequencethrough which a specific gene would be deleted from the cell --the gene for an antigen that leads to cell-mediated rejection ofa transplanted organ by the human immune system. "To deletesuch antigens in all cells in mature animals," Bell said, you"must do so early," in undifferentiated embryonic stem cells.

He said it is "currently not possible to knock out genes in theembryonic phase unless you have stable embryonic stem cells."He added that Alexion has identified antigens in the mature pigthat the company would want to delete to improvetransplantation.

Bell said that transgenic technology used over the past 10years involves microinjection, whereby DNA is injected into anearly cluster of partially differentiated embryonic cells. He saidthe uptake of DNA into the cells is entirely random andproduces different genetic modifications every time.

In comparison, when stem cells are genetically engineered, allsubsequent cells in mature animals include the modificationengineered into the stem cells. This "removes the trial anderror involved in microinjection."

The use of genetically engineered porcine embryonic stem cellsshould result in more efficient and more commercially viableproduction of transgenic animals, Bell said. Alexion plans todevelop the embryonic stem cell technology -- in concert withits proprietary technologies targeting cell and complement-mediated rejection -- for the commercialization of products fororgan transplantation and prevention of restenosis. Thecompany said it may ultimately use the same approach togenerate the endothelial cells that form the basis of its Encelprotein drug-delivery system.

In addition to the pig, transgenic sheep, goats and cows havealso been produced. Bell said the pig is the most suitable donorfor transplantation because its organs are anatomically andphysiologically similar to human organs. Bell noted that Alexionbelieves it may be able to transplant pig organs into humansby 1995.

Alexion, a New Haven, Conn.-based biopharmaceuticalcompany, was founded in January 1992. It is focusing on threeareas: development of novel biopharmaceutical, cellreplacement and gene therapy approaches to the treatment ofspecific immunologic, cardiovascular and hematologic disorders;genetically engineered cellular pumps for long-term, systemicprotein drug delivery; and screening for novel anti-inflammatory and anti-infective agents.

Earlier this month, the company announced that it hadobtained a worldwide exclusive license for the use of leukemiainhibitory factor (LIF) in the production of transgenic animalsfrom embryonic stem cells. According to Alexion, "LIF is theonly known growth factor to independently and stablymaintain embryonic stem cells in an undifferentiated state."The company licensed LIF from AMRAD Corp. (AustralianMedical Research Development Corp.) Ltd., an independentbiotechnology company.

-- Brenda Sandburg News Editor

(c) 1997 American Health Consultants. All rights reserved.