1. Plaintiffs File Petition for Certiorari
in AMP V. USPTO (Myriad case)
By Kevin E. Noonan
科碩一 易先勇
• Basic intro.
• Law issue
• Conclusion and feedback
3. Paper Review
• Certiorari: from Latin, means to be informed of gaining
appellate review, ordered and examined by superior court.
Author: Kevin E. Noonan, Ph.D.
• an experienced biotechnology patent
lawyer, a partner of a LLP.
• more than 10 years as a molecular
biologist.
• founding author of the Patent Docs
weblog.
• In 2010, interviewed for a segment
that aired on the television program
"60 Minutes” addressing the issue of
gene patenting.
4. • In AMP. v. USPTO, Public Patent Foundation (PubPat)
and American Civil Liberties Union (ACLU) argued for
plaintiffs.
The Public Patent Foundation at Benjamin N.
Cardozo School of Law (“PUBPAT”) is a not-for-
profit legal services organization whose mission is
to protect freedom in the patent system.
The American Civil Liberties Union (ACLU) is
a nonpartisan non-profit organization with
mission "to defend and preserve the
individual rights and liberties guaranteed to
every person in this country by the
Constitution and laws of the United States.
5. Plaintiffs and Defendants
• Plaintiffs- appellees
• Researchers
• Drs. Kazazian, Ganguly (University of Pennsylvania School of medicine,
Genetic Diagnostic Lab.), Ostrer (New York University)…
• Organizations
• AMP (Association for Molecular Pathology), AMCG (American College of
Medical Genetics)…
• Patients
• Defendants- appellants
• USPTO
• Myriad Genetics, Inc (Salt Lake City)
• former co owner and exclusive licensee
• UURF (The University of Utah Research Foundation)
• an owner or part owner of each patent.
• Amici
• American Medical Association, American Society of Human
Genetics…
6. Case History
Federal District Court of
Southern District of New
York (S.D.N.Y.)
Issued on 3/29.2010
Mayo Collaborative Services v.
Prometheus Laboratories,
Inc.(C.A.F.C)
Federal Court of Appeals,
Federal Circuit (C.A.F.C.)
Issued on 7/29.2011
PubPat & ACLU
Petition for Certiorari near
12/08, 2011
Certiorari granted in light of Mayo Collaborative Services v.
Prometheus, on 3/26, 2012, oral Prometheus
Laboratories, Inc.(S.C) issued on
argument held on 6/20, 2012 3/20,2012
7. Background
• In 1990, one gene that
correlated with increased
risk of breast and/or ovarian
cancer was located in the
body on chromosome 17.
Some of these researchers
formed Myriad in 1991.
• In 1994, Myriad, along with
researchers from NIEHS,
Univ. of Utah, and McGill
University, sequenced the
cancer gene, and named
“BRCA1”.
• Later, Myriad found another
gene named “BRCA2” in
1995, and obtained series of
patents of BRCA1/2.
8. Background
• In 1998~ 2008, Myriad charges
about $3000 for BRCA1/2 test.
.
• In 2008, revenues are $222 million,
of which $190 million in profit.
• In contrast, the Ontario regional
public health plan offering
BRCA1/2 testing - in disregard of
the Myriad patents –charges about
$1000/test.
• Through cease and desist letters,
communication person in person,
licensing and litigations…Myriad‟s
act of enforcing its patent right was
widely known in the research
community.
9. Isolated DNA
Extracted or purified
cDNA
DNA
• Isolated DNA refers to a segment of DNA nucleotides
existing separate from other components normally
associated with native DNA.
• DNA with isolated DNA
• Common
• same information
• Difference
• structurally and chemically difference, like introns
• usage different as probes or primers
11. Main Issue
• Patent Eligibility
• Are human gene patentable?
• Standing Requirement
• Did the court err in adopting a new and inflexible rule that contradict
to MedImmune, Inc. imposing a more rigid requirement for
standing?
13. Category1: Isolated, non- mutated forms,
and fragments of BRCA1/2 gene
• Claim 1 of the „282 patent
• An isolated DNA coding for a BCRA1 polypeptide, said polypeptide
having the amino acid sequence set forth in SEQ. ID. NO: 2.
• Claim 2 of the „282 patent
• The isolated DNA of claim 1 ,wherein said DNA has the nucleotide
sequence set forth in SEQ ID NO: 1.
• Claim 5 of the „282 patent
• An isolated DNA having at least 15 nucleotides of the DNA of claim1.
• Claim 6 of the „282 patent
• An isolated DNA having at least 15 nucleotides of the DNA of claim2.
• Claim 1 of the „492 patent
• An isolated DNA molecule coding for a BRCA2 polypeptide, said DNA
molecule comprising a nucleic acid sequence encoding the amino acid
sequence set forth in SEQ ID NO: 2.
14. Category2: BRCA1/2 genes containing
mutations
• Claim 1 of the „473 patent
• 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.
• Claim 7 of the „282 patent
• An isolated DNA selected from the group consisting of :
• (a) a DNA having the nucleotide sequence set forth in SEQ. ID. NO: 1 having T at nucleotide
position 4056;
• (b) a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having an extra C at
nucleotide position 5385;
• (c) a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having G at nucleotide
position 5443; and
• (d) a DNA having the nucleotide sequence set forth in SEQ ID NO:1 having 11 base pairs at
nucleotide position 189-199 deleted.
• Claim 6 of the „492 patent
• An isolated DNA molecule coding for a mutated form of the BRCA2 polypeptide set
forth in SEQ. ID. NO:2, wherein said mutated form of the BRCA2 polypeptide is
associated with susceptibility to cancer.
• Claim 7 of the „492 patent
• The isolated DNA molecule of claim 6, wherein the DNA molecule comprises a
mutated nucleotide sequence set forth in SEQ. ID. NO:1.
15. Category3: Methods analyzing an individual‟s BRCA 1
gene to determine inherited mutations
• Claim 1 of the 999‟ patent
• A method for detecting a germline alteration in a BRCA1 gene, said
alterations set forth in Table 12A, 14, 18 or 19 in a human which
comprises
• analyzing a sequence of a BRCA 1 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.
16. Category4 : Methods comparing patients‟ BRCA1/2 gene with the
normal, and examination to determine a potential therapeutic
compound
• Claim 1 of „001 patent
• A method for screening a tumor sample from a human subject for a
somatic alteration in a BRCA1 gene in said tumor which comprises
• gene comparing a first sequence selected from the group consisting of a
BRCA1 from said tumor sample, BRCA1 RNA from said tumor and
BRCA 1 cDNA made from mRNA from said tumor sample with
• a second sequence selected from the group consisting of BRCA1 gene
from a non- tumor sample of said subject, BCRA1 RNA from said non-
tumor sample and BRCA1 cDNA made form mRNA from said non-tumor
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 cDNA from said non- tumor sample indicates a
somatic alteration in the BRCA1 gene in said tumor sample.
17. • Claim 1 of „441 patent
• 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 rom said sample with
• germline sequence of wild- type BRCA1 gene, wild- type BRCA1 RNA
or wild- type BRCA 1 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 the said subject.
18. • Claim 1 of „857 patent
• 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
sequence identifies a mutant BRCA2 nucleotide sequence.
• Claim 2 of „857 patent
• 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.
19. • Claim 20 of the „282 patent
• A method for screening potential cancer therapeutics which
comprises
• growing a transformed eukaryotic host cell containing an altered BRCA1
gene causing cancer and 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 the
said compound and comparing the growth rate of said host cells,
wherein a slower rate of said host cell in the presence of said compound
is indicative of a cancer therapeutic.
20. Patents
• U.S.C 35, section 101
• Whoever invents or discovers any new and useful process,
machine, manufacture, or composition or matter, or any new and
useful improvement thereof, may obtain a patent therefore, subject
to the conditions and requirements of this title.
• Novelty, section 102
• Non- obvious, section 103
• Utility
• Utility Examination guidelines
• Statutory subject matter
21. Exceptions of Section 101
• from Diamond v. Chakrabarty,
• Laws of nature
• Natural phenomena
• Abstract Idea
In General Electronic, a In Funk Brothers, a mixture
purified tungsten couldn‟t be of bacteria couldn‟t be
patented, since it ”existed in patented, since it “did not
nature and doubtless has create a state of inhibition or
existed for centuries.” of non- inhibition.”
Patentable subject must be markedly different from a product of
nature, which means it must possess a new or distinctive
from, quality or property.
22. Judgment of the court
- composition matter
D.A. C.A.F.C.
• What makes DNA unique not • The claim covers molecules that
only its chemical structure, but hardly exist in natural status.
also the information it conveys. • The isolated DNA is free of some
• Isolated DNA may serves as other components in the cell.
probes or primer. Why it can • For example, BRCA2
serve so results from the without introns shrink to just
sequence it carries. 10,200 nucleotides in
• The different chemical structure comparison with those
are just the result of purification. normal with introns can
have near 80,000
nucleotides.
Not Patentable Patentable
23. Machine and Transformation Test
• Use to determine whether a mental process or patentable
subject. From Bilski to Prometheus, two prongs:
• (1) It is tied to a particular machine or apparatus, or
• (2) It transforms a particular article into a different state or thing.
In addition, the use of specific machine or transformation must
impose meaningful limits on the claim‟s scope, and the involvement
of a machine or transformation must not merely insignificant extra-
solution activity. (e.g. data gathering)
24. Example : Prometheus
• Claim in Prometheus:
• A method of optimizing therapeutic efficacy for treatment of an
immune- mediated gastrointestinal disorder, comprising:
• (a) administering a drug providing 6- thioguanine to a subject having
said immune- mediated gastrointestinal disorder, and
• (b) determining the level of 6- thioguanine in said subject having said
immune- mediated gastrointestinal disorder,
wherein the level of 6- thioguanine less than about 230 pmol per 8x108
red blood cells indicates a need to increase the amount of said drug
subsequently administered to said subject and
wherein the level of 6- thioguanine greater than about 400 pmol per 8x108
red blood cells indicates a need to decrease the amount of said drug
subsequently administered to said subject.
25. Example : Prometheus
• Transformation exist as human body as well as the
chemical and physical changes of the drug‟s metabolites.
• The “determining” step alone was transformative and
central to the claimed method since determining the levels
of the metabolites in a subject necessarily involves a
transformation, for those levels can‟t be determined by
mere inspection.
26. Example: Grams
• The method consisted of two step:
• (1) performance of clinical laboratory tests on an individual to
obtain data for the parameters, and
• (2) analyzing the data to ascertain the existence and identify of an
abnormality…
• No transformative step on human subject.
• Court held that the essence of what was claimed was the
mathematical algorithm for analyzing the clinical data, and the sole
physical process- laboratory testing was merely data- gathering to
obtain clinical data.
27. Judgment of the court
- method
D.A.
(Category 3,4)
(claim 20 of 282‟ patent)
• The words “Analyzing and comparing”, in contrast
to “determining the metabolite level ”, refers to
only abstract mental process. • Viewed in entirety, the
• “From a human subject” or “from a non- tumor essence of the claim is
sample ” in the claim only serves to identify the that comparing a slower
DNA. growth rate to indicates a
• The word “analyzing and comparing” even cancer therapeutic.
seemed as include “isolating and sequencing Inserting DNA or
human DNA”, it won‟t be central to the purpose of
compound into host cells
claim.
• Without specifying how about the words can only be regarded as
“analyzing and comparing” impose no meaningful preparatory data
limitation on the claim. gathering step.
Not Patentable
28. Judgment of the court
- method
C.A.F.C
(Category 3,4)
• Reasoning as D.A.
Not Patentable
(claim 20 of 282‟ patent)
• Tie to specific host cells transformed with BCRA gene.
• Satisfying the transformation test, including these transformative steps:
• 1. host cells growing with a altered BCRA1 gene
• 2. determine growth rate with or without the compound
• 3. these steps are central to the claimed process
Patentable
29. Standing requirement
• Declaratory Judgment:
• Real and substantial, definite and concrete, having adverse legal
interests.
• Controversy of sufficient immediacy and reality to warrant the
issuance of declaratory judgment.
• Lujan v. Defenders of Wildlife (Standing)
• Suffering some actual or threatened injury as a result
• The injury must be fairly traceable to the challenge action
• The situation is likely redressed by a favorable decision
• MedImmune v. Genentech
• From actual infringement to “apprehension of litigation”
• All circumstances test: whether the facts alleged, consider all the
circumstances, show that there is a substantial controversy…
30. Standing requirement
• Affirmative Act by the defendants
• A requirement that there be a specific, affirmative act directed
toward the plaintiff to establish standing to seek a declaratory
judgment of patent invalidity would be inconsistent with the S.C.
mandate that “all facts alleged, under all the circumstances…”
• Meaningful preparation
• “Ready, willing and able” to infringe and that such expressions of
desire and ability are sufficient to establish standing…
31. Judgment of the court
- standing
D.A. C.A.F.C.
• Myriad constituted a • Only three plaintiffs‟ injury
“widespread understanding” that traceable to Myriad, since
one may engage BCRA testing affirmative enforcement toward
at the risk of being sued for them.
infringement liability • Others only took consideration,
• Plaintiffs‟ desire and ability to but Dr. Ostrer show unequivocal
engage testing is clear. intent to restart testing. (real
• The researchers and patients and immediate injury or threat)
are deterred from BRCA testing • Plaintiffs failed to show patients
because of Myriad. judicially cognizable injury due to
denial of health service…
Everyone has standing One Dr. Ostrer has standing
33. Conclusion
• C.A.F.C. established a rigid criteria toward standing.
• Gene still be regarded as a composition patent subject
matter.
• Note: In Prometheus, S.C ruled:
• The step in claim process involved well- understood, routine, and
conventional activity previously engage in the research field.
• Upholding the patent would risk disproportionately tying up the use
of underlying natural laws.
34. Feedback ＆ Discussion
• The standing requirement?
• Better rigid
• 節省訴訟資源
• Should human gene be patentable?
• Criteria: Vague (markedly different? central?)
• 考慮分配正義
Thank you for your listening
