By Lisa PierceyWashington Editor

WASHINGTON _ The U.S. Patent and Trademark Office (PTO)has issued a broad patent covering ex vivo human gene therapy toresearchers from the National Institutes of Health (NIH).

The patented technology was developed under a 1988 CooperativeResearch and Development Agreement (CRADA) between the NIHand Genetic Therapy Inc. (GTI), of Gaithersburg, Md. As a result,GTI has been granted an exclusive license to commercialize thetechnology.

News of the NIH patent and GTI's exclusive position was greetedwarmly by Wall Street on Tuesday. GTI's stock (NASDAQ:GTII)closed at $10, up $1.50 (17 percent) per share. But experts andanalysts in the field of gene therapy challenged the depiction of thepatent as seminal or as having an extensive immediate economicimpact. In addition, it's unclear whether the broad patent canwithstand challenges.

If the NIH patent does hold, it could potentially have far-reachingconsequences. Of the more than 100 early-stage gene therapy clinicaltrials currently under way in the U.S., the vast majority use ex vivogene therapy technology. A number of biotechnology companies,among them Somatix Therapy Inc., of Alameda, Calif., and TargetedGenetics Corp., of Seattle, have invested heavily in the field.

GTI president and CEO James Barrett told BioWorld that the NIHpatent "clarifies the proprietary landscape in gene therapy" and couldattract investors and collaborators to his firm. "We have certainduties under our license from NIH with respect to licensingstrategies," said Barrett. "Our obligation is to undertake a licensingstrategy that maximizes the speed at which these products (ex vivogene therapy products) get to the marketplace."

Ex vivo gene therapy is based on the premise that acquired diseasesand genetic defects may be treated by introducing the correct versionof defective or missing genes into patients. The ex vivo approachinvolves extracting cells from a patient, inserting a gene expressing atherapeutic protein into the cells, and then reinjecting the geneticallyaltered cells into the patient.

The first evidence that such an approach might work was thesuccessful treatment in 1990 of two children who suffer from a rareblood disorder known as adenosine deaminase deficiency (ADA).NIH researchers French Anderson, Michael Blaese and StevenRosenberg conducted the study in conjunction with GTI. The threescientists are listed as inventors on the NIH patent.

ADA sufferers carry an incorrect version of the ADA gene whichrenders them unable to fight even mild forms of infection. AfterAnderson and his team treated the children, they were able toproduce ADA on their own. Both girls now lead relatively normaland healthy lives.

"What we provided was the proof-of-principle that gene therapy cantreat disease," said Anderson, who is currently a professor ofbiochemistry and pediatrics at the University of Southern Californiain Los Angeles. "We showed that gene therapy works and that's whywe got the patent." Anderson serves as a consultant to GTI and ischairman of the company's scientific advisory board.

Curiously, the results of the NIH-GTI trial still have not beenpublished in a major scientific, peer-reviewed journal. According toAnderson, the four-year-old data is now in the process of beingsubmitted to the Science.

According to GTI, the NIH-GTI collaboration and the ADA trialform the basis of the NIH patent, No. 5,399,346. It covers "the use ofhuman cells [such as, for example, but not limited to, human bloodcells] as vehicles for the transfer of human genes encodingtherapeutic agents and/or gene encoding detectable markers."

Brandon Fradd, a biotechnology analyst at Montgomery Securities inSan Francisco who covers GTI, said the NIH patent and GTI'sexclusive position affirm the company's "leading position in the fieldof gene therapy." But he predicted that it would neither haveimportant commercial implications nor attract investors to the field ofgene therapy, which they have abandoned in the last year.

"We saw interesting results in the ADA children but we haven't seena lot of direct or sustained cures since then," said Fradd. "Genetherapy is complex and people realize that it's off in the future. It willbe a year or two before we even see pivotal trials launched for genetherapy products."

An Unfavorable Affect On Other Companies?

Fradd said the NIH patent might adversely affect companies likeSomatix that have focused on ex vivo gene therapy. But Somatixchief financial officer Mark Bagnall said it's too early to judge thestrength of the NIH patent. His firm has a number of broad patentscovering ex vivo gene therapy for specific cell types in Europe, aswell as one in the U.S. that covers the genetic modification ofepithelial cells.

The existence of Somatix's issued patents, as well as two pendingpatents with file dates earlier than the NIH patent, "throws intoquestion for GTI how well the [NIH] patent will hold," according toBagnall.

"In order to practice gene therapy, companies will need a wide rangeof gene therapy intellectual properties," said Bagnall.

Anderson argued that his patent, which underwent five years ofreview at the PTO, likely will withstand challenges. "I know that thepatent office examined this patent all the way up to the level of thecommissioner's officer and back again before they felt comfortablewith its breadth," he said. "They reviewed it for a full year after theprimary examiner had made her initial recommendation just to besure."

Robert Abbott, president and CEO of San Diego-based Viagene Inc.,which focuses on in vivo gene therapies, told BioWorld that theimpending patent brouhaha may be much ado about nothing. "Thewhole industry is trending toward in vivo gene therapy becausepeople understand that ex vivo approaches are going to be toocostly," he said. Case in point: Somatix recently bought privatelyheld Merlin Pharmaceutical Corp., based in Research Triangle Park,N.C., because it had an attractive in vivo program.

Analysts said the real test for ex vivo and in vivo gene therapies alikeremains, will they work and can you sell them? The answer to thatquestion may not be forthcoming for five to 10 years. n