analysis
Abbott asserts in the suit that Folkman
signed the agreement; however, Folkman
maintains that although he signed the
agreement, it was ultimately stopped at
the hospital’s technology transfer office
and never returned to Abbott.
anti-proliferative effect of various plas-
minogen kringle fragments on endothelial
cells (Cao et al., 1996, 1997), Abbott
never claimed that it represented an
invention of Davidson or the company,
Folkman said. Abbott realised only later
that kringle 5 had anti-angiogenic poten-
tial. According to Folkman, Abbott is
seeking to invalidate Folkman’s patent on
kringles 1–5 because it allegedly dis-
covered kringle 5’s unique properties.
Abbott disputes that its involvement was
late, and is seeking not only to invalidate
Folkman’s patent, but is also alleging that
he seeks to appropriate intellectual prop-
erty that he does not own.
This is not the first time that doubt has
been cast on Folkman. In November
1998, a journalist at the Wall Street
Journal reported that no lab could verify
Folkman’s animal data using endostatin,
another anti-angiogenic compound dis-
covered in his lab. Soon after, however,
this was shown to be untrue when a
number of labs demonstrated that
Folkman’s results were correct and repro-
ducible.
the market in the USA. Compared with its
product range, Abbott has only a small anti-
cancer pipeline, but one on which it may
be trying to build. Kringle 5 is its first anti-
angiogenesis compound and it recently
obtained the rights for another anti-cancer
compound from Eisai Co. in Japan.
Abbott’s strong interest in anti-angiogenic
drugs is easily understood given that ∼20
other angiogenesis inhibitors are now
being tested in phase I and II clinical trials
news/angio/table.html).
Such a change in the company’s
research direction may also be seen in its
recent hiring of Jeffrey Leiden from Har-
vard Medical School, for whom it created
the new position of chief scientific officer.
Soon after, Abbott announced a new
management structure and moved Leiden
to head the pharmaceutical business. This
movement indicates that it could be gear-
ing up to move its drug business ahead
swiftly; an anti-angiogenesis compound
that is more powerful than angiostatin
would certainly bring Abbott good press
and could serve as a cornerstone for its
revitalised oncology line.
Now it is up to the courts to decide
whether Abbott or Children’s Hospital is
right. But it will certainly not be the end of
lawsuits against scientists in an industry
that is increasingly using courts to obtain
control over important molecules. And
given the publicity surrounding this case,
scientists in academia may become less
willing to cooperate with Abbott or other
drug companies that may question their
integrity in seeking profits from shared
discoveries.
Abbott tried and failed three times to
obtain exclusive control of kringle 5,
Folkman’s countersuit states. Abbott’s suit
claims that Children’s Hospital and Folk-
man had entered into a written agreement
giving Abbott rights to discoveries, in
exchange for receiving waste plasmino-
gen samples for research, in November
1995. Children’s Hospital maintains that
the document was never signed and
returned to Abbott, but that Abbott
deleted hand-written criticisms by Chil-
dren’s Hospital officials, and submitted it
as evidence of an agreement. Children’s
Hospital’s patent was issued in July 1997,
at which time Abbott saw that its efforts to
obtain control of kringle 5 would not suc-
ceed. A few months later, Abbott con-
tacted Children’s Hospital, demanding all
rights to its patent. A year of negotiations
left both sides with no agreement, and
then after a period of quiet, Abbott filed its
suit in May 2000.
Folkman’s lab has discovered five com-
pounds to date, all of which are licensed
to biotech companies and none of which
Folkman stands to profit from financially.
Indeed, Folkman has little to lose in this
fight except his reputation—but in sci-
ence that is nearly everything a researcher
can have.
Folkman has little to lose in this
fight except his reputation — but
in science that is nearly
everything
Abbott’s strong interest in anti-
angiogenic drugs is easily
understood given that ∼20
angiogenesis inhibitors are now
being tested in clinical trials
In its suit, Abbott maintains that
Davidson was the first to discover the
anti-angiogenic properties of kringle 5.
The company states that Davidson
learned that cleaving plasminogen with
elastase for long periods yields a novel
kringle 5 fragment, with a different
sequence. Abbott asserts that this version
of kringle 5 has greater anti-angiogenic
potency than angiostatin or the other krin-
gle fragments. Furthermore, the lawsuit
states that Folkman congratulated Henkin
on this discovery, said that he had over-
looked kringle 5 and told Henkin to file
patents on it.
While Folkman concedes that his group
did not see remarkable properties in krin-
gle 5 and is happy to see Abbott develop
it into a cancer drug, he says that the com-
pany owes Children’s Hospital royalties
on the plasminogen fragment. When Cao
and others published their article on the
Cao, Y. et al. (1996) Protein kringle domains of
human angiostatin. Characterization of the
anti-proliferative activity on endothelial cells.
J. Biol. Chem., 271, 29461–29467.
Cao, Y., Chen, A., An, S.S.A., Ji, R.W., Davidson,
Abbott, on the other hand, stands to gain
considerable financial advantages if it
obtains patent rights on kringle 5. With US
$5 billion a year in sales, Abbott ranks only
16th of the top 20 international drug com-
panies. While its budget for research and
development is less than other drug mak-
ers, it does have a reputation for being an
aggressive litigator. Abbott waged a costly
war to stop Zenith Goldline Pharmaceuti-
cals from marketing a generic version of its
US $500 million a year drug Hytrin, which
is used to treat non-cancerous growth of the
prostate gland. It also faced an antitrust suit
for trying to keep this company’s drug off
D. and Llinas, M. (1997) Kringle
5 of
plasminogen is a novel inhibitor of endothelial
cell growth. J. Biol. Chem., 272, 22924–
22928.
O’Reilly, M.S. et al. (1994) Angiostatin: a novel
angiogenesis inhibitor that mediates the
suppression of metastases by a Lewis lung
carcinoma. Cell, 79, 315–328.
Vicki Brower
The author is a freelance science writer in New
York, NY.
E-mail: vickibrower@cs.com
DOI: 10.1093/embo-reports/kvd080
302 EMBO Reports vol. 1 | no. 4 | 2000
© 2000 European Molecular Biology Organization