By Kevin
E. Noonan —

After
issuing its decision in Bilski v. Kappos,
the Supreme Court granted certiorari,
vacated the Federal Circuit's decision below, and remanded to the appellate
court two cases related to medical diagnostic claims:  Prometheus
Laboratories, Inc.  v. Mayo Collaborative Services and Classen
Immunotherapies, Inc. v. Biogen Idec.  These cases have the
most-developed case law regarding the question of patent-eligibility for
diagnostic method claims, and thus can be expected to provide the Federal
Circuit with ample opportunity to craft the type of analytical framework
envisioned by the Supreme Court when it left the development of the law in this
area to the Federal Circuit (in the first instance, at least).

It is
another case, however, that may provide the first instance for the Federal
Circuit to "make law" under Bilski v. Kappos.  That case is Association
of
Molecular Pathology v. U.S. Patent and Trademark Office (aka the Myriad
case).  As a reminder, method
claims from the following U.S. Patents were invalidated by the District Court
Judge Robert W. Sweet's decision:  U.S. Patent  Nos. 5,747,282; 5,709,999; 5,710,001; 5,753,441;
and 6,033,857.  These patents are assigned to Myriad Genetics, the University of Utah Research
Foundation, and the National Institutes of Health (the '282, '001 and '441
patents); Myriad Genetics, Centre de Recherche du Chul, and the Japanese Cancer
Institute (the '999 patent); and Myriad Genetics, Endo Recherche, HCS R&D
Ltd. Partnership, and the University of Pennsylvania (the '857 patent).  All but the '857 patent claims priority to an application filed August 12,
1994; all but the '857 patent will expire (upon timely payment of
maintenance fees) in 2015 (the '857 patent expires March
2017).

The
following method claims have (for now) been invalidated:

For the '282
patent:

20. 
A method for screening potential cancer therapeutics which comprises: 
growing a transformed eukaryotic host cell containing an altered BRCA1 gene
causing cancer in the presence of a compound suspected of being a cancer
therapeutic, growing said transformed eukaryotic host cell in the absence of
said compound, determining the rate of growth of said host cell in the presence
of said compound and the rate of growth of said host cell in the absence of
said compound and comparing the growth rate of said host cells, wherein a
slower rate of growth of said host cell in the presence of said compound is
indicative of a cancer therapeutic.

For the '999
patent:

1. 
A method for detecting a germline alteration in a BRCA1 gene, said alteration
selected from the group consisting of the alterations set forth in Tables 12A,
14, 18 or 19 in a human which comprises analyzing a sequence of a BRCA1 gene or
BRCA1 RNA from a human sample or analyzing a sequence of BRCA1 cDNA made from
mRNA from said human sample with the proviso that said germline alteration is
not a deletion of 4 nucleotides corresponding to base numbers 4184-4187 of SEQ
ID NO:1.

For the '001
patent:

1. 
A method for screening a tumor sample from a human subject for a somatic
alteration in a BRCA1 gene in said tumor which comprises comparing a first
sequence selected form the group consisting of a BRCA1 gene from said tumor
sample, BRCA1 RNA from said tumor sample and BRCA1 cDNA made from mRNA from
said tumor sample with a second sequence selected from the group consisting of
BRCA1 gene from a nontumor sample of said subject, BRCA1 RNA from said nontumor
sample and BRCA1 cDNA made from mRNA from said nontumor sample, wherein a
difference in the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from said
tumor sample from the sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA from
said nontumor sample indicates a somatic alteration in the BRCA1 gene in said
tumor sample.

For the '441
patent:

1. 
A method for screening germline of a human subject for an alteration of a BRCA1
gene which comprises comparing germline sequence of a BRCA1 gene or BRCA1 RNA
from a tissue sample from said subject or a sequence of BRCA1 cDNA made from
mRNA from said sample with germline sequences of wild-type BRCA1 gene,
wild-type BRCA1 RNA or wild-type BRCA1 cDNA, wherein a difference in the
sequence of the BRCA1 gene, BRCA1 RNA or BRCA1 cDNA of the subject from
wild-type indicates an alteration in the BRCA1 gene in said subject.

And for
the '857 patent:

1. 
A method for identifying a mutant BRCA2 nucleotide sequence in a suspected
mutant BRCA2 allele which comprises comparing the nucleotide sequence of the
suspected mutant BRCA2 allele with the wild-type BRCA2 nucleotide sequence,
wherein a difference between the suspected mutant and the wild-type sequences
identifies a mutant BRCA2 nucleotide sequence.

2.  A
method for diagnosing a predisposition for breast cancer in a human subject
which comprises comparing the germline sequence of the BRCA2 gene or the
sequence of its mRNA in a tissue sample from said subject with the germline
sequence of the wild-type BRCA2 gene or the sequence of its mRNA, wherein an
alteration in the germline sequence of the BRCA2 gene or the sequence of its
mRNA of the subject indicates a predisposition to said cancer.

If
the Federal Circuit merely applies the rubrics (such as they may be) of the
Supreme Court's Bilski decision to
these claims, it seems that only claim 20 of the '282 patent clearly falls
within the scope of the machine-or-transformation (MOT) test.  The claim requires growth of
transformed human cell in the presence or absence of a test compound.  "Transformation" (or to put
it another way, "the hand of man") could be found either in the
production of a transformed eukaryotic host cell or the growth of such a cell in the presence of a test compound.  Since neither the transformed host cell (which should remain patentable per se under the Court's Chakrabarty decision) nor growth in the
presence of a test compound would occur without human intervention, recitation
of these elements in the claim could be enough for the Federal Circuit to
reverse the District Court's decision based on principles enunciated by the
Supreme Court in Bilski and other
precedent.  This result would also
serve not to "disturb the settled expectations of the patent community" (Festo Corp. v. Shoketsu Kinzoko Kogyo Kabutshiki Co., 122 S. Ct. 1831, 1841 (2002)), since such claims are not unique to this
patent but form the basis for many screening method patents (see, for example, U.S. Patent Nos.
7,736,862; 7,727,731; 7,700,822; 6,960,558; 6,682,920; and 5,344,846, as well
as 1760 other such patents).

The other
claims may not fare as well, in view of language that tracks more closely with
the claims in the patents at issue in the Classen
and Laboratory
Corp. v. Metabolite Labs., Inc. (LabCorp) cases (thereby raising
issues relating to form and substance in determining whether an invention is
patent-eligible).  Each of Myriad's
remaining claims invalidated by the District Court recite "comparing"
steps that are not expressly tied to determining the genetic sequence of an
individual's BRCA1 or BRCA2 genes.  Specifically:

• "analyzing
a sequence of a BRCA1 gene or BRCA1 RNA from a human sample or analyzing a
sequence of BRCA1 cDNA made from mRNA from said human sample" (claim 1, '999
patent)

• "comparing
a first sequence selected form the group consisting of a BRCA1 gene from said
tumor sample, BRCA1 RNA from said tumor sample and BRCA1 cDNA made from mRNA
from said tumor sample with a second sequence selected from the group
consisting of BRCA1 gene from a nontumor sample of said subject, BRCA1 RNA from
said nontumor sample and BRCA1 cDNA made from mRNA from said nontumor sample"
(claim 1, '001 patent)

• "comparing
germline sequence of a BRCA1 gene or BRCA1 RNA from a tissue sample from said
subject or a sequence of BRCA1 cDNA made from mRNA from said sample with
germline sequences of wild-type BRCA1 gene, wild-type BRCA1 RNA or wild-type
BRCA1 cDNA" (claim 1, '441 patent)

• "comparing
the nucleotide sequence of the suspected mutant BRCA2 allele with the wild-type
BRCA2 nucleotide sequence" (claim 1, '857 patent)

• "comparing
the germline sequence of the BRCA2 gene or the sequence of its mRNA in a tissue
sample from said subject with the germline sequence of the wild-type BRCA2 gene
or the sequence of its mRNA" (claim 2, '857 patent)

Arguments could
certainly be made that in each case the patient sample sequence must be
determined, which would involve the "transformative" steps of obtaining
the sequence (involving inter alia
cloning or amplifying patient-specific genomic or cDNA and sequencing the DNA,
all involving multiple chemical transformations).  However, the question may be framed with regard to whether
these claims require such transformative steps, or whether they are broad
enough to encompass mere comparison of sequences previously obtained; under this analysis, the sequence steps
may be viewed as mere "data gathering" and hence not satisfy the MOT
test.

Alternatively,
even if these claims are not sufficiently transformative to satisfy the MOT
test, the Supreme Court's Bilski decision provides another avenue for the
Federal Circuit to reverse the District Court's decision that these claims are
not patent-eligible.  This analysis
comes from the portion of the majority opinion (joined by Justice Scalia)
instructing that its prior precedent (specifically the Benson/Flook/Diehr trilogy) reinforced the principle
that abstract ideas are not patent-eligible subject matter.  The task for the Federal Circuit, then,
would be to determine whether these Myriad claims were sufficiently broad to
claim an abstract idea or a "broad concept" that would "wholly pre-empt"
a law of nature, or as in Diehr be "an application of a law of nature"
to a process and thus be worthy of patent protection.

One distinction
that can be drawn in this regard is that in Bilski (and Diehr) the "law
of nature" (hedging in Bilski, the Arrhenius equation in Diehr) were known in the prior art; indeed, the majority opinion in Bilski found that Bilski's claims were
directed towards "basic concept of hedging, or protecting against risk: 'Hedging is
a fundamental economic practice long prevalent in our system of commerce and
taught in any introductory finance class,'" citing (now Chief) Judge Rader's
dissent in In re Bilski, 545 F. 3d,
at 1013.  In Myriad's claims the "law
of nature," the presence of a specific mutation at a specific position in
the nucleotide sequence of the BRCA1 or BRCA2 gene, was unknown prior to its elucidation by the Myriad inventors.  (On the other hand, a claim to a single
nucleotide polymorphism (or SNP) itself could encompass the "natural
phenomenon" or "law of nature" itself and have precisely the
preclusive effect disparaged by the Court in Bilski and earlier precedent.)

It is clear that Myriad's method claims raise many of the same
issues of patent-eligibility as in Classen
and LabCorp.  How the Federal Circuit resolves those
issues, and whether the Supreme Court is more willing to let the Federal
Circuit make these decisions under Chief Judge Rader than it was under Chief
Judge Michel, will determine the extent to which genetic diagnostic claims
remain patent-eligible.  And
consequently whether "unforeseen innovations," like personalized
medicine, will be developed under the patent regime (with enabling disclosure
attendant thereto) or be limited to alternative protections (such as trade secret)
for which disclosure is antithetical and with all the resulting costs and
disadvantages thereof.  Which path
is taken will determine the rate, scope, and benefits of such new technology for
at least a generation.