By
Kevin E. Noonan —

With
the U.S. Supreme Court set to consider the patent-eligibility of claims to
isolated human DNA in AMP v. Myriad
Genetics this morning, another aspect of Myriad’s control over BRCA testing
technology is being contested.  As
reported on Friday by Gina Kolata in the New
York Times ("DNA Project Aims to Make Public a Company's Data in Cancer Genes"), a group headed by Dr. Robert Nussbaum, Chief of the
Division of Genomic Medicine, University of California at San Francisco has started
an effort to "recreate" Myriad’s database of mutations (in addition
to those disclosed in its patents) that are predictive for increased risk of
breast or ovarian cancer.

The
genesis of this effort, termed Sharing Clinical Reports, stems from Myriad’s
decision in 2004 to keep such information proprietary.  Myriad says its decision was based on misuse
of the information in its database, which was intended for research use but was
being used for patient diagnostics, a particularly sensitive area where such
uncertainties can exist.  As a
consequence of its patents restricting BRCA gene testing, Myriad has developed
a proprietary database of such "new" mutations, including ones of "unknown
significance" (i.e., that have
not been associated with risk prognosis) as well as mutations having predictive
capability.  (The Times article reports that the frequency of such "unknown
significance" mutations was 40% in 1996, 20% in 2004 and 3% today, without
attributing these figures.)  While there
have been more than ten thousand basic research reports published in academic
and medical journals since the time Myriad’s patents were granted, it is
undoubtedly the case that there are undisclosed mutations known only to Myriad.

As
reported in the Times, proponents of
the effort are contacting physicians having patients who have received the
Myriad test and thus have received a Myriad test report.  The requests are initially for the
information to be donated, but the effort is sufficiently well funded that
offers of thirty-three cents per report are being made.  (While that doesn’t sound like much, it might
prove expensive if hundreds of thousands or millions of test reports were
involved, as the article suggests.)  Reflecting
the present informal nature of the effort, the article reports that the work of
transmitting the patient test results is done by students "who need extra
money" and that physicians who provide a minimum of 200 variants are
rewarded with an Apple iPad mini.  Present funding is provided by Dr. Peter Kolchinsky, managing director
of RA Capital Management in Boston (which should raise its own set of
motivational questions in Ms. Kolata’s readers).

The
article is, de riguer, replete with
assertions that genetic researchers are "furious," and that Myriad is
preventing second opinion testing (ironically, by the managing director of
GeneDX, "a gene testing company working with Dr. Nussbaum").  [H]aving one company
control the data for genes is contrary to the way medicine is developing,"
according to Heidi Rehm, a Harvard geneticist, who is reportedly also working
with Dr. Nussbaum.  As detailed in the article, Dr. Rehm is apparently referring
to "whole genome sequencing," which creates a situation where there
are "22,000 genes" and "50
million variants" (which, even if true, is irrelevant to the subject under
discussion, the two human BRCA genes and their mutations and variants).  And as might have been expected, the group is
requesting the National Institutes of Health start a publicly funded database
of all variants of all human genes studied.

Nonetheless,
the group raises an important issue.  As
has been reported here previously, one aspect of the gene patenting debate routinely
ignored is that the genetic information is not patented.  Accordingly, the Sharing Clinical Reports
effort is in no sense "illegal" (provided that the provisions of the
Health Insurance Portability and Accountability Act, HIPAA, regarding patient
confidentiality are not transgressed) nor should it raise patent infringement
liability for the group.  If Myriad had
amassed its database using proprietary means, or if trade secret
misappropriation were involved, the company might have a way of preventing any
effort to obtain the genetic data produced by such proprietary means.

Here,
Myriad elected to enjoy the benefits of patent protection, wherein it could
prevent anyone else from making, using, selling, offering to sell or importing
its inventions.  In return, Myriad was
required to disclose those inventions pursuant to the provisions of patent law
that require a written description of the invention that enables a person of
skill in the art to practice the invention after the patent(s) expire
throughout the full scope of the claims, and to disclose the best mode of
practicing the invention (the latter requirement having been significantly
blunted by the Leahy-Smith America Invents Act).  And there is no allegation that Myriad did
not properly satisfy these requirements, at least with regard to the mutations
it had identified when it filed the applications that were eventually granted
as its patents.

These
disclosure requirements do not apply with regard to any "new"
mutations contained in Myriad’s database, for the simple reason that they were
unknown at the time these applications were filed.  Indeed, there is no requirement in patent law
to supplement a patent specification unless new inventions are claimed.  But the advantages Myriad enjoys (and that "infuriate"
the geneticists so) were procured based on the exclusivity provided by the
patents, and these advantages will persist after the patents expire.  These facts raise the question of whether
there is any aspect of this situation that would constitute "patent
misuse," a concept used as a defense to a charge of patent infringement
that involves (relevant to this discussion) extending patent exclusivity after
the expiration of the patent term.  While
the situation typically arises in patent licensing, it is reasonable to ask
whether the policy drivers behind the defense have any relevance to the
situation here, which can be expected to arise for any genetic diagnostic
patents (exclusively or non-exclusively licensed), provided there is no
obligation to make public or at least share new genetic information generated
during the patent exclusivity period.

The
answer is not to ban patents on isolated DNA (which are not infringed by
genetic diagnostic methods in any event) or genetic diagnostic methods per se.  This is because the policy-based obligation, if any, arises from the
patent grant itself and the quid pro quo
of disclosure in exchange for such exclusivity.  Abolishing the exclusivity would abolish the obligation, and would
provide incentives for companies to disclose as little information as
possible.  Instead of identifying the
mutations now sought by Dr. Nussbaum and his colleagues, for example, future
(unpatented) genetic diagnostic methods could come merely with the information
that a patient has a genetic mutation associated with an increased risk of a
particular disease, with statistics on survival and treatment options and their
success rates but no information on
which mutation(s) were involved.  While
this outcome would be even more inconsistent with the way genetic diagnostics
is and has been developing than Myriad’s behavior bemoaned by Dr. Rehm in the
article, what patients and their doctors want most are reliable diagnostic
results, and a company offering such advanced diagnostics would be in a
position to adopt a "take it or leave it" attitude regarding
disclosure.  This possibility is even
more likely for the majority of diseases that, unlike breast cancer and BRCA
are multivariate and less readily reverse engineered.

These
considerations are not amenable to judicial intervention (despite rumors that
at least one of the legal proponents of the Myriad
case is planning to file such a lawsuit).  Congress could intervene, but any bill would need to provide the right
balance between return on investment (said to be more than $500 million by
Myriad) and public access to information during and after the relevant patent
term.  Any such attempt to legislate will
also require less rhetoric and more problem solving than has been evident in
the gene patenting debate, which in large part involves physicians demanding
the right to freely infringe genetic patents in the name of patient
rights.  Of course, none of these
physicians is proposing to perform these tests for free, and that of course is
one of the distinctions between these physicians and the researchers behind the
10,000 scientific research papers on the BRCA genes.  Regardless of the outcome of the Myriad case before the Supreme Court
(which, no matter how it turns out, will have little to no effect on
availability of genetic diagnostic testing for the BRCA genes), addressing the
policy considerations involving human genetic diagnostics is something that
will remain.  While the politics of
confrontation generates headlines and contributions to those who paint
themselves as patient champions, it has done and will do little to resolve
these important issues.