Download AMP v. Myriad – Brief History

The Future of Gene Patents: Patenting
DNA and Other Biological Molecules
and Products Following the Supreme
Court’s Decision in AMP v. Myriad
Genetics
Christopher L. Wight
DNA Primer: What is DNA?
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The Central Dogma of Molecular Biology:
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DNA→RNA→mRNA→Protein (exist in nature)
DNA Primer: What is cDNA?
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cDNA (non-naturally occuring)
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Recombinant protein
Patent Eligibility Before AMP v. Myriad
35 U.S.C. § 101 – Patent Eligibility
Whoever invents or discovers any new and useful
process, machine, manufacture, or composition of
matter, or any new and useful improvement thereof,
may obtain a patent therefor, subject to the conditions
and requirements of this title.
Patent Eligibility Before AMP v. Myriad
35 U.S.C. § 101 – EXCEPTIONS
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Laws of nature – E=MC2
Products of nature – salt
Natural phenomena – gravity
Abstract ideas – calculus
These are the “basic tools of scientific and technological
work”
Patent Eligibility Before AMP v. Myriad
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What makes something patent eligible?
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Any non-trivial act of human intervention
Product is distinguishable from anything in nature
Isolation of biomolecule from native source
Example: Protein purified from human tissue, having
therapeutic benefits not possessed by native form
Patent Eligibility Before AMP v. Myriad
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Isolated DNA
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Separated from other DNA
Ability to sequence purified/concentrated DNA
Isolated proteins
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Separated from other biomolecules
Increased specific activity (confers additional utility
as a therapeutic)
AMP v. Myriad – Brief History
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U.S. Patent No. 5,747,282
1. An isolated DNA coding for a BRCA1 polypeptide having the
amino acid sequence set forth in SEQ ID NO:2 [the BRCA1
protein/amino acid sequence].
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Claim defines isolated DNA by its functional ability to
encode a BRCA1 protein sequence
Both genomic DNA and cDNA encode BRCA1 protein
DNA claims held to be ineligible for patent protection
AMP v. Myriad – Brief History
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U.S. Patent No. 5,747,282
2. The isolated DNA of claim 1, wherein said DNA has the
nucleotide sequence set forth in SEQ ID NO:1 [cDNA
sequence that encodes BRCA1].
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Claim defines isolated DNA by its structural nucleotide
sequence
cDNA claims held to be eligible for patent protection
AMP v. Myriad – Brief History
Majority Opinion (Justice Clarence Thomas)
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HOLDING: “Myriad did not create anything. To be sure, it
found an important and useful gene, but separating that
gene from its surrounding genetic materials is not an act of
invention”
COMPROMISE: “cDNA does not present the same
obstacles to patentability as naturally occurring, isolated
DNA segments… creation of a cDNA sequence from
mRNA results in an exons-only molecule that is not
naturally occurring”
cDNA is “synthetically created”
“…the lab technician unquestionably creates something
new when cDNA is made”
AMP v. Myriad – Brief History
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Only “new” compositions are patent eligible
Mere isolation is not enough to render a natural
product “new”, absent some other human intervention
that goes beyond merely isolating from natural
environment
AMP v. Myriad – Brief History
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What was Supreme Court’s rationale for patent
ineligibility of isolated DNA?
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Isolated DNA merely “cleaved” from genomic DNA (insufficient
physical modification)
Isolated DNA retains the genetic information embodied in
cellular DNA
AMP v. Myriad – Brief History
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What was Supreme Court’s rationale for patent
eligibility of cDNA?
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cDNA is “synthetically created”
cDNA has a different physical structure than genomic DNA (it
omits introns)
AMP v. Myriad – Scope of Holding?
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Products isolated from natural environment invalid?
Isolated proteins from humans, animals, plants?
Antibiotics from microbes?
Stem cells?
Synthetically created versions?
DNA having high sequence similarity?
AMP v. Myriad – Ambiguities?
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Naturally occurring – produced naturally and isolated
from its native environment (i.e., isolating DNA from
saliva or a blood sample)
vs.
Synthetically created – made by a non-natural (i.e.,
human contrived) process (i.e., synthetic DNA
produced from PCR process, or DNA made from
expression of recombinant DNA molecule)
AMP v. Myriad – Ambiguities?
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Is ALL synthetically created DNA patent eligible (i.e.,
synthetically amplified by PCR)?
Myriad claims cover “isolated” DNA, but not limited to
“synthetic” DNA
While “synthetic” DNA may retain genetic information,
it is in fact structurally different (i.e., lacks epigenetic
modifications, such as methylation of cytosine and
adenine DNA molecules, typically found in genomic
DNA)
AMP v. Myriad – Ambiguities?
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cDNA is “synthetic” in the same sense that PCR
amplified DNA is “synthetic”
Structural difference between cDNA and mRNA
(thymine replaced by uracil, differing by only a single
methyl group) is comparable to structural differences
between genomic DNA and synthetic DNA (addition of
methyl group to cytosine or adenine DNA nucleotides)
AMP v. Myriad – Impact on Patenting DNA
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Isolation of a biomolecule, produced naturally in a
biological organism, probably not enough to confer
patent eligibility
“Synthetic” molecules, having common or similar
sequence or structure, probably patent eligible
AMP v. Myriad – Impact on Patenting Protein
Therapeutics (or signal interfering DNA)
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Myriad case held that invalidated claims “are simply
not expressed in terms of chemical composition, nor
do they rely in any way on the chemical changes that
result from the isolation of a particular section of DNA”
DNA having similar sequence to genomic DNA may be
patent eligible if there are structural differences in the
synthetic DNA, and such structural differences are
recited in the claim
AMP v. Myriad – Impact on DNA Diagnostics
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PCR-based amplification
Nucleotide probes (short sequences complementary to
and capable of hybridizing to template DNA, used to
initiate sequencing)
AMP v. Myriad – Impact on Other Biological
Discoveries (i.e., Stem Cells)
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Consumer Watchdog v. Wisconsin Alumni Research Foundation,
No. 13-1377 (Fed. Cir. 2013).
Appeal from holding of USPTO Board of Patent Appeals, which
confirmed patentability of claims in U.S. Patent No. 7,029.913.
Issue of patent eligibility raised for first time on appeal.
ISSUE: Are cultured human embryonic stem cells (hESCs)
markedly different from naturally-occurring hESCs?
Does the process of culturing the cells provide the cells “with
markedly different characteristics from any found in nature?”
CW asks Fed. Cir. to apply holding of Myriad to in vitro cultured,
human embryonic stem cell cultures, and find them ineligible for
patent protection under 35 U.S.C. 101.
AMP v. Myriad – Impact on Other Biological
Discoveries (i.e., Stem Cells)
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WARF’s U.S. Patent No. 7,029,913
1. A replicating in vitro cell culture of pluripotent human
embryonic stem cells derived from a pre-implantation embryo,
wherein the stem cells (i) will proliferate in an in vitro culture for
over one year in an undifferentiated state without the
application of exogenous leukemia inhibitory factor, (ii)
maintain a karyotype in which the chromosomes are euploid
through prolonged culture, (iii) maintain the potential to
differentiate to derivatives of endoderm, mesoderm, and
ectoderm tissues throughout the culture, (iv) are inhibited from
differentiation when cultured on a fibroblast feeder layer.
AMP v. Myriad – Impact on Other Biological
Discoveries (i.e., Stem Cells)
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WARF argues that claim recites “in vitro cell culture” – clearly not
a “product of nature”
Expert witness for WARF further testified that the morphology of
the hESCs are different from prior art mouse ES cell colonies
(hESC colonies are flatter and more compact)
CW argues that the claims “merely identify properties that are
inherent in all ES cells, including those that exist naturally” and do
not recite either a method of preparation or a scientific application
of the claimed composition.
Practical Advice
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Recite additional limitations beyond mere isolation
Significantly altering molecular structure to improve function or
biological activity
Synthesize biomolecule in such a way as to alter physical
properties or biological activity
Comparative testing of “isolated” naturally occurring molecule vs.
synthetically created molecule
Culturing self-replicating organisms (ex vivo) in a manner different
from natural environment
Practical Advice
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Artificially engineer a biomolecule with other biomolecules
Example - Amgen’s ENBREL®, a dimer of two extracellular
domains of TNF receptor molecule linked to each arm of an Fc
domain of IgG1 antibody (extends half-life and increases
biological activity)
Contact Info
Christopher L. Wight
Bateman IP Law Group
257 East 200 S., Suite 750
Salt Lake City, Utah 84111
Web: www.BatemanIP.com
Phone: (801) 533-0320
Email: [email protected]