By Debbie Strickland

Everyone knows that if an orchid's going to grow in Alaska in January, it had better be sheltered in a climate-controlled, lighted environment similar to that of its natural, tropical habitat. No matter how much it's fertilized, an orchid isn't going to sprout in the permafrost.

Human stem cells likewise won't grow outside their natural habitat inside the bone marrow unless that habitat is meticulously recreated, said Aastrom Biosciences Inc., which has exclusive rights to a patented medium-exchange method for culturing the cells ex vivo.

According to the Ann Arbor, Mich., company, four new allowed and issued patents "describe fundamental technology for either the ex vivo growth or genetic modification of human stem cells to be used for the restoration of damaged or diseased tissues [such as] bone marrow, blood and immune system cells, bone cartilage and connective tissue."

Among the broadest claims, according to R. Douglas Armstrong, Aastrom's president and CEO, are these two, in an allowed patent:

* An ex vivo cell culture composition in which a substantial number of human stem cells originating from a human hematopoietic system have undergone ex vivo cell division as a result of the conditions in a medium-exchange ex vivo culture.

* An ex vivo human hematopoietic or stromal stem cell composition in which a substantial number of human hematopoietic or stromal stem cells have undergone ex vivo cell division as a result of the conditions in a medium-exchange ex vivo culture.

In other words, said Armstrong, his company owns the rights to the medium-exchange-cultured ex vivo dividing and/or divided stem cells themselves.

Aastrom, which funded basic science research that produced the technology, has an exclusive license to the patents, owned by University of Michigan.

"These four patents together . . . give us quite a unique patent status in the industry," Armstrong said. "Most of the major pharmaceutical companies" are affected, he told BioWorld Today.

Armstrong cited Novartis AG, of Basel, Switzerland; Chiron Corp., of Emeryville, Calif.; Genzyme Corp., of Cambridge, Mass.; Hoechst AG, of Frankfurt, Germany; Schering AG, of Berlin; and Rhone Poulenc Rorer, of Collegeville, Pa.

"Given that they have an interest in these areas, there is a very strong opportunity for some collaborations to move forward," the CEO said, adding, "We don't look at this as a means to force everybody to stop their businesses and come to us. The patents allow us to move forward in a protected fashion . . . We want to move therapies forward, not prevent them from happening."

Aastrom said it has a lock on stem cell reproduction, but CellPro Inc., of Bothell Wash., also announced a patent allowance covering stem cell expansion.

"What our patent really covers is expansion using specific cytokines," said Joann Reiter, spokeswoman for CellPro. "Our patent covers the expansion of stem cells. I can't give an opinion on how it does or does not interact with Aastrom's."

CellPro already markets a device that separates stem cells — the Ceprate SC Stem Cell Concentration System — approved for processing autologous bone marrow to obtain a stem cell-enriched population for hematopoietic support after myeloablative therapy.

That device is the subject of a patent dispute with Baxter International Inc., of Deerfield, Ill., whose Isolex cell separation system goes before an FDA advisory panel today.

As for Aastrom's culturing technology, it has an array of potential applications, including gene therapy, treatments using umbilical cells, cartilage restoration and — the lead indication — post-chemotherapy stem cell replacement.

The stem cell therapy market currently consists of chemotherapy-related bone marrow stem cell extraction and replacement. At high doses, and when used in combination with each other, chemotherapeutic treatments also destroy the stem cells in a patient's bone marrow. These cells can be restored by infusion of stem cells collected from the patient or donor before cancer treatment is administered.

This market alone is worth more than $500 million a year and is growing by 20 percent annually, according to analyst David Stone, of Cowen & Co., in Boston.

CellPro's and Baxter's separation systems are aimed at this market — they separate stem cells from other materials, including tumor cells — but Aastrom's system could offer an added advantage: the extraction procedure takes one outpatient visit of less than two hours, providing, the company said, significant savings of time, pain and money over other separation techniques.

According to trial results announced in May, Aastrom's Cell Production System (CPS) grew bone marrow cells from a small amount of material, retaining the stem and other key immune cells needed to restore tissues destroyed by aggressive cancer treatments.

The company plans to initiate a multicenter pivotal trial soon, to support marketing applications in the U.S. and Europe. The device would be marketed (in late 1999 or early 2000) in the U.S. by Lakewood, Colo.-based COBE BCT, a subsidiary of Sweden's Gambro AB and owner of a 24 percent equity stake in Aastrom. The CPS may be approved earlier in Europe, where a trial is under way.

Aastrom's shares (NASDAQ:ASTM) closed Wednesday at $6.875, down $1.25. *