[Pharm-policy] Hepatitis C Virus Patent Dispute

[James Love]

Interesting (but somewhat dated) account of patent dispute involving a
former CDC official and Chiron Corp.  Jamie

http://www.bioinfo.com/rotavirus.html

Hepatitis C Virus Patent Dispute (article from February 1995 Antiviral
Agents Bulletin)

Dr. D.W. Bradley, formerly with the Centers for Disease Control and
Prevention (Atlanta, GA), has filed suit against Chiron Corp.
(Emeryville, CA), challenging the status of its recently issued U.S.
patent (5,350,671) covering hepatitis C virus (HCV) clones, diagnostics
and vaccines. Dr. Bradley seeks to invalidate the patent, have himself
included as a co-inventor and receive damages and royalty income from
Chiron. The suit filed in the Northern District of California (San
Francisco, CA) also names several Chiron officials and scientists and
Ortho Diagnostics Systems (a subsidiary of Johnson & Johnson Co.;
Chiron's partner in HCV diagnostics marketing) as defendants. The
Department of Health and Human Services (parent of CDC) is an
involuntary defendant, cited for a 1990 agreement with Chiron that
conceded all patent rights to Chiron. Dr. Bradley is currently retired
and serves as Chairman, Steering Committee on Polio and Hepatitis
Vaccines, World Health Organization. Note, U.S. patent 5,350,671, "HCV
Immunoassays Employing C Domain Antigens," (for abstract and first
claim, see October 1994 Bulletin, p. 306) was erroneously reported in
Dr. Bradley's court filing and by other publications as U.S. patent
5,530,671.

Dr. Bradley claimed he supplied Chiron with high titer HCV-infected
plasma from infected chimpanzees that was instrumental in Chiron's
isolation and cloning of HCV; that he developed critical findings about
the virus, including its having an RNA genome and an envelope; and that
he provided Chiron with assistance regarding cloning methods,
specifically concerning the use of lambda gtll expression screening. Dr.
Bradley began work on what was then called non-A, non-B hepatitis (later
to be designated HCV) in 1977, joined CDC in 1982 where he primarily
worked on HCV and continued there until last year. He is acknowledged as
having first infected chimpanzees with HCV and demonstrating that
chimpanzees develop hepatitis symptoms and are a useful animal model for
study of HCV. Dr. Bradley claims he provided Chiron with "over 2,500 ml
of a very rare commodity, a unique commodity," namely HCV-infected
chimpanzee plasma that was essential to Chiron's isolation and cloning
efforts. Dr. Bradley shared in much of the scientific recognition and
several awards for his contribution to the cloning of HCV.

The dispute between Dr. Bradley and Chiron can be traced back to 1986
when the parties failed to agree on terms for Dr. Bradley to provide
infected plasma to Chiron. The disagreement continued and was
exacerbated in 1988 when Chiron announced its cloning of the HCV genome
(and failed to include Dr. Bradley on its patent applications). Dr.
Bradley's complaint alleges that NIH (which handles most patent matters
for CDC) proposed to Chiron that it should receive co-ownership of HCV
patents based on Dr. Bradley's contribution, in exchange for which NIH
would grant the company a 3% royalty for a ten-year period. Chiron
rejected this demand. In 1990, CDC reached a settlement with Chiron (to
which Dr. Bradley was also a party) in which it renounced interest in
HCV patents. In return, Chiron paid $2.25 million to CDC to fund HCV
vaccine research through a Collaborative Research and Development
Agreement (CRADA) for which Dr. Bradley was the CDC's principal
investigator and agreed to personally pay Dr. Bradley $67,500/year for
five years in recognition of his contributions. However, Dr. Bradley
claims he was not a party to these negotiations and alleges he "signed
the agreement under duress," lacking a full understanding of its
consequences and was concerned about providing for his family after
recently being diagnosed as having prostate cancer. A legal review of
Dr. Bradley's claims was included by Chiron in its U.S. patent
submission in 1991.

As is normal and expected in such cases, the parties involved issued
statements supporting their positions and rebutting those of their
adversaries. Chiron alleges that Dr. Bradley's suit is part of a
"desperate strategy" by companies (e.g., Organon Teknika Ltd., Murex
Diagnostics Ltd. and United Biomedical; see October 1994 Bulletin, p.
300) which have been unsuccessful in their challenges of Chiron's HCV
patents in the U.S. and other countries. Dr. Bradley is represented by
the same firm that represents Organon Teknika in its HCV patent
disputes. Chiron claims that Dr. Bradley was not a co-inventor and cites
the March 1990 agreement with both CDC and Dr. Bradley which includes
their abandoning any future HCV patent-related claims against Chiron.
Dr. Bradley's suit alleges that his "victory would save at least $30
million annually in health care costs," presumably through a reduction
in the cost of HCV immunodiagnostics used to screen blood products for
HCV antibodies that would result from government nonexclusive licensing
of HCV patents. The suit also alleges that Chiron "has built a worldwide
reputation and billion-dollar business largely due to Dr. Bradley's
research and inventive ideas. This is a classic example of corporate
greed resulting in an exorbitant cost for public health care and the
diminution of one of those `faceless' government researchers' dedication
to hard work."

Note, Dr. Bradley's co-inventorship claim is primarily based on his
providing HCV-infected plasma to Chiron, not that he performed the
actual cloning, although some of his suggestions may have been adopted
by Chiron, and Dr. Bradley did not directly participate in the
development of cDNA libraries or cloning of HCV by Chiron. The U.S.
patent's claims refer only to HCV compositions (e.g., clones, genes,
antigens) and do not refer to methods used for HCV isolation and
cloning. In general, the supply of raw materials or proposals for
specific procedures are not sufficient to require co-inventorship status
for U.S. patents. As stated by one of Chiron's attorney's, it is highly
unlikely that "merely providing materials or theorizing about the nature
of the virus or the type of procedures necessary for its isolation
constitute qualitative enough contributions to the claimed invention."

Previous patent disputes, particularly between Amgen and Chugai
Pharmaceuticals concerning recombinant erythropoietin (EPO), have
resulted in rulings that generally cite the actual isolation and cloning
of a gene (the claimed invention), not just its purification and general
characterization, as the moment of invention. However, evaluation of the
contributions of individuals still plays a significant role in
determining inventorship rights. Chiron alleges that although Dr.
Bradley may have been right regarding some characteristics of HCV and
his suggestions for action (which were not critical to the actual
invention--HCV cloning and gene sequences), this does not constitute
inventorship. A similar doctrine was recently upheld for the granting of
sole inventorship rights for AZT to Burroughs Wellcome Co. In this case,
NIH researchers provided the technology that enabled screening of AZT
for anti-HIV efficacy and blindly screened AZT and other substances
provided by the company.

-- 
James Love, Consumer Project on Technology
v. 1.202.387.8030, fax 1.202.234.5176
love@cptech.org, http://www.cptech.org