[Ip-health] Science: Tangled Patent Dispute Over 'Free' Drug-Resistance Database

[Matt Price]

http://www.sciencemag.org/cgi/content/full/323/5918/1156

Tangled Patent Dispute Over 'Free' Drug-Resistance Database

Jon Cohen

A patent dispute among a small European biotechnology company,
Stanford University, and one of its HIV/AIDS researchers has triggered
a defamation lawsuit, raised issues of academic freedom, and led some
observers to call it a battle out of Don Quixote.

At the center of the dispute are U.S. patents owned by Advanced
Biological Laboratories (ABL) S.A. in Luxembourg that involve computer
methods to guide treatment of patients with HIV infection and other
diseases. In early 2007, ABL notified Stanford that its popular
Internet-accessible HIV Drug Resistance Database (HIVdb) possibly
infringed two of the company's patents. The HIVdb helps clinicians,
researchers, and drug developers around the world make sense of the
complex array of mutations the virus has developed to dodge specific
treatments. "It's a tremendous tool that takes full advantage of the
power of the Web and marrying sequencing and clinical data," says
HIV/AIDS clinician Daniel Kuritzkes of Brigham and Women's Hospital in
Cambridge, Massachusetts. "I use it every time I'm in the clinic."

Robert Shafer, an infectious-disease specialist at Stanford who began
building the database 10 years ago and receives support from the U.S.
National Institutes of Health and unrestricted grants from industry,
was outraged by ABL's claims. "It's so blatantly wrong," says Shafer.
He claims the patents are overly broad and vague and notes that the
European Patent Office "refused" a similar application in 2006.

Shafer says at first he saw eye to eye with Stanford's attorneys, who
in October 2007 filed for "declaratory relief," essentially asking a
judge to prevent litigation from moving forward. Stanford also told
ABL that it might file reexamination requests with the U.S. Patent and
Trademark Office (USPTO), which can correct or invalidate issued
patents.

The company and the university continued to negotiate and in March
2008 reached a settlement--without Shafer's input. The "immunity
agreement" states that ABL would not file patent-infringement claims
against any party that used the database for noncommercial purposes.
But only people affiliated with Stanford had the right to pursue
commercial activities with the database; anyone else who used it "in
activities for a fee or otherwise in exchange for monetary
consideration" remained subject to ABL's patents. As part of the
agreement, Stanford pledged to post a notice on the HIVdb that said as
much.

Shafer says telling him what to post on his Web site violates academic
freedom and he balked, noting that many companies use the HIVdb to
develop drugs or to support their own commercial tests that help
clinicians make treatment decisions. The agreement, says Shafer,
"gives ABL a green light to go and sue other people. It makes Stanford
complicit and makes me seem complicit."

Five months passed before the Web site posted a notice, which said, in
part, "Stanford does not represent that use of this database would not
infringe patent rights of other persons or entities." To ABL's dismay,
this was not the agreed-upon language, and the notice made no mention
of the company.

Shafer hired his own counsel and on 10 October 2008 filed
reexamination requests with USPTO on the two patents. Twelve days
later, he posted a notice on the Web site that mentioned the company's
patent rights but noted that he had filed the reexamination petitions.
Shafer also included a disclaimer that said he "considers these
patents to be harmful to research on the use of computers in medicine
and is concerned that the recent litigation resulting from these
patents is harmful to the care of persons with HIV infection."

On 1 December, ABL sued both Stanford and Shafer for breach of
contract and defamation. Chalom Sayada, a co-founder of ABL who has
led the company's negotiations with Stanford, says he has "a very deep
and sincere respect" for Shafer's scientific work and the HIVdb. And
he stresses that ABL has attempted to solve these issues amicably.

Sayada, a geneticist who has served as CEO of several other biotechs,
strongly objects to Shafer's allegation that the patents have harmed
research and patients. "We are not aiming to prevent research," he
says. "And we obviously are not looking to harm or prevent the care of
anybody." He adds that clinicians, even though they charge their
patients fees, are free to use the HIVdb without paying licensing fees
to ABL. "We try to be realistic," he says.

Sayada contends that Stanford's and Shafer's actions have hurt ABL's
business. "People are speaking very badly about my company," says
Sayada. And he says USPTO's patent reexamination is the proper venue
to resolve the debate. "Anything beyond this is mere politics, and I'm
not sure who benefits."

Sayada thinks Stanford made a "big mistake" by not involving Shafer
during the original agreement negotiations. Stanford counsel Patrick
Dunkley sees this as a misstep, too. Although the university owns the
database and "had the complete authority to enter into the agreement
without consulting with Professor Shafer," says Dunkley, "in
hindsight, it probably would have been more prudent to have involved
him."

Shafer, who says he has spent more than $100,000 of his own money
pursuing the patent reexaminations and defending himself against ABL's
suit, contends that Stanford set a bad precedent by caving in to ABL's
threats. "The university didn't back down at all," retorts Dunkley.
"What the university did was protect the rights of the research
community, and upon achieving its objective, there was no ongoing
fight to have."

Shafer has peppered many colleagues with e-mails about the dispute and
about restrictive patents in general. This has alienated some
colleagues who see his impassioned battle against allegedly harmful
patents as tilting at windmills. But he has also attracted some strong
support. "As a faculty member who does work precisely in this area, I
was surprised and concerned that the university took the position it
took rather than trying to contest the patent," says Mark Musen, a
Stanford researcher who specializes in biomedical informatics.

USPTO is expected to rule on the patent reexamination requests within
the next few months. Stanford and Shafer have until the middle of
March to respond to ABL's lawsuits. ABL's Sayada has attempted to
engage Shafer in an informal mediation with leading HIV/AIDS
researchers, but Shafer vows to fight to the end. "I'm not doing it
out of spite," says Shafer. "It's a way of a vindication to say,
'Look, you guys were scared, but I fought this and was able to win
this.' I want to show Stanford should have taken a stand."