Transcript Myriad - Tech Transfer Central

Myriad, Metabolite, Bilski, and
Prometheus:
The Four Horsemen of the Biotech
Apocalypse?
Kevin E. Noonan, Ph.D.
McDonnell Boehnen Hulbert & Berghoff LLP
Professor Christopher Holman
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Outline of the Talk
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Introduction
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How did we get here?
AMP v. Myriad Genetics
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Parties and interests
The claims: DNA and methods
The arguments
The court’s decision
Constitutional issues?
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Outline of the Talk
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Labcorp v. Metabolite
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The claims
The Supreme Court argument
The dissent from dismissal of cert
In re Bilski
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The Claims and Federal Circuit decision
How does this relate to biotech?
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Outline of the Talk
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Prometheus v. Mayo Labs
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Claims and issue
The Federal Circuit decision: Diagnostic method
claims can be patent-eligible
Relevance to Myriad decision
Recommendations
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To patent or not to patent
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Introduction
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How did we get here?
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Tremendous success of a technological age
Biotechnology the beneficiary of strong patent
protection
Biotechnology developed in university setting –
1980 Bayh-Dole Act promotes patenting
But success breeds criticism – from variety of
sources
These include political criticism from those
opposed to university patenting
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Where is here?
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Politically-motivated groups in the arena: ACLU
and PubPat
PubPat challenges variety of patents (not just
biotech); notable the WARF human ESC patents
General attitude that patents have become too
powerful and retard innovation (little empirical
support)
Time ripe for Myriad challenge: in addition, the
“right” defendant, due to aggressive patent
enforcement tactics
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AMP v. Myriad
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Myriad: The parties
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Suit brought in May 2009, SDNY (Judge Sweet)
Plaintiffs: several breast cancer victims, variety
of physicians’ groups, certain researchers who
claimed research impeded by BRCA patents
Defendants: University of Utah (patent assignee),
Myriad Genetics, U.S. PTO
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Supporters: ACLU, PubPat, academics
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Seven patents/ 15 claims at issue
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Invalid under patent statute and Constitution
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Myriad: The issue
Patent eligibility versus patentability
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Patent-ineligible means that the subject matter
is not eligible for a patent for public policy
reasons notwithstanding the fact that it may
be patentable (i.e., useful, novel, and not
obvious).
Patentable subject matter means the invention
as claimed is useful, novel, and not obvious.
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Myriad: The claims
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Two broad types of claims at issue: claims to
isolated DNA molecules, and diagnostic method
claims
DNA claims recite “isolated” DNA encoding
specific amino acid sequences (cDNA)
Also claims to oligonucleotide probes
Method claims: methods of detecting mutation or
providing a diagnosis/risk assessment
Method claims involve “comparing” mutant
sequence to normal sequence
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Myriad: The claims
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Composition of matter claims covering “isolated
DNA” covering the BRCA 1 and BRCA 2 genes.
Claim 1 of US Patent 5,747,282 is representative
of this class of claims:
An isolated DNA coding for a BRCA1 polypeptide, said
polypeptide having the amino acid sequence set forth
in SEQ ID NO:2.
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Myriad: The claims
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Composition of matter claims covering “isolated
DNA” covering the mutations of BRCA 1 and
BRCA 2 genes. Claim 1 of US Patent 5,693,473
is representative of this class of claims:
An isolated DNA comprising an altered BRCA1 DNA
having at least one of the alterations set forth in
Tables 12A, 14, 18 or 19 with the proviso that the
alteration is not a deletion of four nucleotides
corresponding to base numbers 4184-4187 in SEQ.
ID. NO:1.
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Myriad: The claims
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Methods of detecting mutations in the BRCA
genes. Claim 1 of US Patent 5,709,999 is the
only claim in this class:
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
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Myriad: The claims
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Methods that “compare” and “correlate” mutations
in the BRCA genes with an increased risk of breast
or ovarian cancer. Claim 2 of US Patent 6,033,857
is representative of this class of claims:
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.
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Myriad: The arguments
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Regarding the DNA claims, plaintiffs argue that
they are “products of nature” and hence not
“inventions”
No Supreme Court case that DNA patent-eligible
Precedent (19th century, subject to
interpretation) that “supports” their view
Method claim arguments based on Bilski
Constitutional argument: violation of 1st
Amendment right to biological information and
14th Amendment due process
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Myriad: The decision
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Judge Sweet agrees that DNA an unpatentable
“product of nature”
DNA is “the physical embodiment of genetic
information”
Distinguishes other types of “natural products”
(antibiotics, vitamins) on this basis
Method claim invalid on Bilski
Constitutional arguments avoided, Patent Office
dismissed from the lawsuit
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Myriad: The Constitution
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Although the judge avoided, still important
Quickest way to get the Supreme Court’s
attention
Depends on a failure to appreciate that the
information isn’t what is patented in claims to
isolated DNA
However, information is implicated in method
claims, because that is what a diagnostic method
claim produces – diagnostic information
Should it matter?
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Myriad: Remaining claims
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A vector comprising isolated DNA operative in a host
cell.
A host cell containing isolated DNA and control
sequences
Methods for producing BRCA1 polypeptide comprising
culturing cells and harvesting the BRCA1 polypeptide
A kit for detecting mutations in the BRCA1 gene
A nucleic acid probe specifically hybridizable to BRCA1
DNA
The method that amplifies all or part of a BRCA1 gene
and sequences the amplified BRCA1 nucleic acids.
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Patentability of Diagnostic
Methods
Labcorp v. Metabolite
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Labcorp Claim
Claim 13.
A method for detecting a deficiency of
cobalamin or folate in warm-blooded animals comprising
the steps of:
assaying a body fluid for an elevated level of total
homocysteine; [a “detecting” step] and
correlating an elevated level of total homocysteine in
said body fluid with a deficiency of cobalamin or folate
[an “inferring” step].
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Labcorp dissent - context
General problem of “determine and infer”
claims (Prof. Kevin Emerson Collins):
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Characterized by one or more “determining” steps
that involve assays, etc. = transformative
Include “mental step” of reaching a conclusion or
arriving at an inference based on outcome of
determining steps
Claim preamble directs method to activity (e.g.,
diagnosing) based on inference
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Supreme Court argument
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Defendant argued that the claim was not
patent-eligible, because it was merely mental
activity directed at making a diagnosis
Raised the issue of patents interfering with
medicine (surgical techniques earlier lost
patent infringement liability)
Methods that occur wholly in the mind, by
“correlating” or “comparing” should not be
patented
Supreme Court argument
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Justices heard the arguments, then decided
(for procedural reasons) that the Court
should not have heard the case
Justices Breyer, Souter and Stevens dissented
from this decision
Justice Breyer’s dissent based on his
acceptance and agreement with defendants’
argument that the claims not eligible for
patenting
Labcorp dissent
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“As construed by the Federal Circuit, claim 13 provides those researchers with
control over doctors' efforts to use that correlation to diagnose vitamin
deficiencies in a patient. Does the law permit such protection or does claim
13, in the circumstances, amount to an invalid effort to patent a
‘phenomenon of nature’"?
“At most, respondents have simply described the natural law at issue in the
abstract patent language of a ‘process.’ But they cannot avoid the fact that
the process is no more than an instruction to read some numbers in light of
medical knowledge.”
“[H]ere, aside from the unpatented test, they embody only the correlation
between homocysteine and vitamin deficiency that the researchers
uncovered. In my view, that correlation is an unpatentable ‘natural
phenomenon,’ and I can find nothing in claim 13 that adds anything more of
significance.
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Labcorp dissent
Justice Breyer misses a few points of
well-established patent law:
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Whether a claim recites patent-eligible subject
matter does not depend on whether the claim
is itself patentable
Applications of “phenomena of nature” are
patentable; the phenomenon itself is not
Patent eligibility of a claim must be
determined from the claim “as a whole”
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In re Bilski
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In re Bilski: The claims
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Claims directed to a method for hedging risk in
commodities trading
Rejected by the patent examiner, affirmed by the
patent board of appeals
Federal Circuit (appellate court that hears these
appeals) agrees, announcing a new test
A method to be patentable has to either
Be tied to a particular machine or
Transform a particular article into a different
state or thing
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Supreme Court weighs in
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Does not reject Federal Circuit test, but says it is
not the only test
Goes back to first principles, relating to whether
what is claimed is an abstract idea that preempts every use thereof
Benson/Flook/Diehr precedent, wherein
applications of abstract ideas are patent-eligible
but not if the idea is completely pre-empted
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But MOT test “should be satisfied” is most cases
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How does Bilski apply to biotech?
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MOT test not limited to “business methods”
Test required for any method, including
diagnostic methods
Typical diagnostic method is not tied to a
particular machine
Many diagnostic methods (like in Metabolite)
involve using data to make a diagnosis, so don’t
“transform”
Also based on medical knowledge – is this an
“abstract idea”?
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Prometheus Labs v. Mayo
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Consequences of Bilski Decision
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Prometheus Labs v. Mayo (decided September 16,
2009)
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Claims a method for optimizing treatment of an immune-mediated
gastrointestinal disorder with 6-thioguanine
Recited steps of administering the drug to a patient and detecting
6-thioguanine or 6-methyl-mercaptopurine (metabolite) in blood
Recites inferring step of therapeutic efficacy when 6-thioguanine
levels in red blood cells are between 230 pmol-400 pmol per 8 x
108 red blood cells
Levels outside these ranges “indicates a need” to adjust
administration amounts accordingly – but does not recite
affirmative steps of adjusting
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Prometheus Labs v. Mayo
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Steps for administering a drug and determining
metabolites can be transformative and satisfy Bilski
Such steps can be “method of treatment” steps that
are “always transformative”
Involving “natural processes” not determinative,
since “every transformation of physical matter . . .
occurs as the result of natural processes”
A process for chemical or physical transformation of
a physical object or substance are “virtually selfevidently” patent-eligible subject matter
Inclusion of a mental step does not negate patenteligibility
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Prometheus Labs v. Mayo
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In the wake of Bilski, the Supreme Court
granted cert, vacated the Federal Circuit
decision and remanded
Mayo has asked the court for en banc review
No matter what the Federal Circuit decides,
expect appeal to Supreme Court
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Consequences and the Future
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Recommendations:
Isolated DNA claims
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If “isolated” is insufficient, many DNA claims
invalid
Consequences depend on what the claims
are protecting
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For making therapeutic proteins, recombinant
cell claims should survive
Vector claims should also be patentable (manmade)
Kit claims should also be patentable, as
manufactures
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Recommendations:
Diagnostic Method claims
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Fate of diagnostic method claims may be
language-dependent
Insofar as claim can be cast as “merely
mental step” then at greater risk
“Correlating”/“comparing” language
problematical
Claims containing more active steps (like
“sequencing”) may be at lower risk
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Recommendations:
Diagnostic Method claims
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Bigger problem for these claims (even if
they survive Bilski /Prometheus decisions)
Potential for a patent “thicket”
Some efforts around this (patent pooling,
SNP consortium, Navigenics “ASCAP”
solution)
Will get worse before it gets better,
particularly regarding personalized medicine
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Recommendations: Ways forward
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Patented technology
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Licensing
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Litigation
New technology
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To patent or not to patent
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Recommendations:
Patented technology
 “Narrowing” reissue a possibility
 For DNA claims, can limit to
“manufactured” DNA – claim scope
expressly outside chromosomal DNA by
structure
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Can also narrow vector claims to these
embodiments
Diagnostic method claims to include
“active” steps like sequencing
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Recommendations:
Patented technology
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In litigation, DNA claims not usefully
asserted
But then, what damage (usually) from DNA
claim alone?
Recombinant cells should survive Myriad
even at Supreme Court
Pharmaceutical infringement should involve
at least use of recombinant cells
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Recommendations:
New technology
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Patenting may not be an option (or at least
be unattractive)
For industry, when you cannot patent, trade
secret becomes attractive
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Not easy, but attractive
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But may be worth the risk and investment
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Broad (and negative) implications for
academic research
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“Old” technology
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BRCA1 and BRCA2 the anomalous – many
common diseases (diabetes, most cancers,
cardiovascular disease) multigenic
Requires detection of more than one
dominant mutant gene
Not difficult to identify “disease” genes
But may be difficult to obtain sufficient
correlations between several genes to be
useful
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Recommendations:
New technology
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Academia versus industry: what industry
does better
Focused investigation to determine which
genes in combination are diagnostic
Wealth of genetic data (thanks, Human
Genome Project) + large reservoirs of
frozen tumor and other tissue
Capacity to use both for to develop assays
for making diagnostic decisions
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Recommendations:
Diagnostic methods/ trade secrets
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With existing technology, can analyze tens
of thousands of frozen normal and diseasespecific tissue samples
Identify the differences between normal and
disease that are common in disease
Perform prospective study on normal/
diseased cohorts to show predictive power
Assemble roster of disease-specific genes
for a particular disease
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Recommendations:
Diagnostic methods/ trade secrets
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Diagnostic test is “gene chip” containing
>10,000 sequences
Some of these are specific for the disease
(multiple sequences from different genes)
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Some are positive controls
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Some are negative controls
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All are assembled on the chip “randomly” –
positions encrypted for each chip
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Recommendations:
Diagnostic methods/ trade secrets
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Encryption informs reader which sequences
are determinative for disease
Billions of permutations, (almost)
impossible to decipher/reverse engineer
Showing of reliability may be required, but
identity of genes should not be
FDA issues regarding extent of disclosure
required, but alternative may be no test at
all
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Recommendations:
Diagnostic methods/ trade secrets
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Consequences:
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Academia/industry collaborations over
Research-intensive efforts preclude global
approaches
Pace of genetic research on diseases slows
Disclosure disappears
No disclosure = no need to reduce prices ever
Fundamentally shifts progress (negatively)
and incentives to innovate
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Recommendations:
Possible alternative
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Industry abandons the space entirely
Diagnostic genetic testing done in university
or hospital settings exclusively
Concentrated in large medical centers, with
advantages and disadvantages:
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Test consistency and reliability concerns
Relationship to university mission
Best use of resources
Availability/cost of genetic counseling
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Recommendations:
Diagnostic methods/ trade secrets
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Exchange of powerful incentives
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Today, early-stage, research-intensive,
high-risk research
Tomorrow, focused, disease-specific
research by industry to develop diagnostic
products
Provides rationale/explanation to counter
“free is good” arguments
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Conclusions
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Situation very unsettled
No clear and unambiguous path forward
Myriad appeal on track, appellant briefs due
in October
Prometheus will most likely be the next
opportunity for a Supreme Court decision
Possible that the Court will let the Federal
Circuit flesh things out in a few cases before
granting cert
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Thank you!
Kevin E. Noonan, Ph.D.
[email protected]
www.patentdocs.org
MBHB
300 South Wacker Drive
Chicago, Illinois 60606-6709
312 913 0001 phone
312 913 0002 fax
www.mbhb.com
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