Patents
and
Clinical Genetics
Rebecca Rae Anderson, J.D., M.S., C.G.C.
University of Nebraska Medical Center
College of Public Health
Dilbert’s I.P. experience
SACGHS
Office of Science Policy – NIH
Secretary’s Advisory Committee on
Genetics, Health and Society
Gene Patents and Licensing Practices and
Patient Access to Genetic Tests (Public
Consultation Report March 2009)
Appendix 1: Case Studies
Duke University Center for Genome Ethics, Law
& Policy
What we’ll discuss:
Can you really patent a gene?
What is a genetic patent, anyway?
How have genetic patents affected
clinical genetics?
What can we expect in the future?
Can you really patent a gene?
Article 1 Section 8
Congress shall have power . . .
to promote the progress of
science and useful arts, by
securing for limited times to
authors and inventors the
exclusive right to their respective
writings and discoveries.
Can you really patent a gene?
37 USC§101.
Inventions
Patentable. 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.
Can you really patent a gene?
Can you really patent a gene?
Patent number
Inventors
Current owners
Filing history
Field of art
Abstract
‘487 Inventors & Assignees
‘487 Timeline
‘487 Abstract
‘487 Drawings
‘487 Enablement
‘487 Claims
‘487 Claims
2. A purified normal CFTR RNA . . .
3. A purified . . . cDNA.
4. A purified DNA molecule . . . Comprising
a DNA sequence encoding an amino acid
sequence depicted in Fig 1 . . .
5. A detectably labeled normal CFTR probe,
comprising . . . At least 16 contiguous
nucleotides . . .
6. A normal CFTR probe . . .
‘487 Claims
‘487 Claims
‘487 Figure: CFTR Sequences
~4,400 sequence patents by 2007
What’s the fuss?
Monopoly?
Anti-commons?
Hold-outs?
Cross-blocking?
Defensive patents?
Gendia
What’s
the
fuss?
Adam Brandejs
art installation
ca.2006
Canavan – Miami Children’s
Retrospective royalties
$25 per test (later $12.50)
Few academics (<100 assays)
One large commercial lab
Salon.com Who owns
your DNA? 3-7-2000
Jonathan & Amy Greenberg Judith Tsipis, M.S.
Greenberg v. Miami Children’s
264 F Supp 2d 1064 (S.D. Fla. 2003)
Lack of informed consent
Breach of fiduciary duty
Unjust enrichment
Fraudulent concealment
Conversion
Misappropriation of trade secrets
Canavan – Miami Children’s
"My understanding from the
hospital was we needed to file
the patent just so I could work
with the gene myself," says
Matalon, who has since
moved to the University of
Texas hospital system, where
he continues to work on
Canavan disease. "I had
nothing to do with their
licensing decision and I got no
penny from any patent.”
Dr. Reuben Matalon
Salon.com Who owns
your DNA? 3-7-2000
Science, Aug 2004
Hereditary Deafness
Athena
A1555G
35delG
Connexin
26
Sublicense
Connexin
26

Connexin
26 D50N
GeneDX
-- KID
Pediatrix newborn screen
BRCA1-2 -- Myriad
Dr. Mark Skolnick
70’s Ph.D: Utah Population Database
200,000 Mormon families
1.6 million descendents of original
10,000 settlers
Linked w/ Utah Cancer Registry
40,000 hits
BRCA1-2 -- Myriad
BRCA1 co-inventors at University of Utah, NIH
Assigned to University of Utah
Exclusively licensed to Myriad
BRCA2 purchased by Myriad from OncorMed
Sole provider of BRCA1 – 2 sequencing in US
Begins w/ full gene sequencing $3120
Mutation-specific for family members $300
Aggressive enforcement
BRCA1-2 -- Myriad
Slow uptake of new technology?
Large deletions found by French group
Now part of Myriad package
Inability to get ‘second opinion’?
Inflated prices / lack of access?
Suppression of research?
At-cost sequencing for investigators: $1200
Undue advantage in finding new mutations
BRCA1-2 – Myriad
Inflated cost?
Gene
BRCA1
BRCA2
APC
MLH1
MSH2
MSH6
Amplicons
35
47
42
19
16
25
Size
81,155
84,193
108,353
57,359
80,098
23,807
BRCA1-2 – Myriad
cost per amplicon
BRCA1-2
Full seq (2)
82
Myriad
$3,120
$38.05
FAP
Full seq (1)
42
Baylor
Boston
Harvard
Huntington
U Pennsylvania
Mayo
Myriad (44 amplicons)
$1,675
$1,675
$1,500
$1,200
$1,360
$1,300
$1,795
$39.88
$39.88
$35.71
$28.57
$32.38
$30.95
$40.80
HNPCC
Full seq (3)
60
Baylor
Boston
City of Hope
Harvard
Huntington
Mayo
Myriad
U Pennsylvania
Quest Diagnostics
$3,200
$2,995
$4646.16
$2,700
$1,800
$3,100
$2,950
$2,840
$4,760
$53.33
$49.92
$77.44
$45.00
$30.00
$51.67
$49.17
$47.33
$79.33
Medibic Life Sciences
Remedies? Challenge Rules
Fed Register 66(4)1092-1099 Jan 5, 2001
Discoveries (vs. inventions) not patentable
Genes are products of nature
Shouldn’t patent core of personhood
Patent on gene sequence is overbroad
Contrary to indigenous law / 13th amendment
Patents are delaying medical research
Sequence per se has little utility
Sequence per se inherently useful
Scope should be limited to methods, applications
Scope should be limited to disclosed uses
Sequences are now routine and thus obvious
Patent genes only when completely characterized
Reject computer-based conjectural gene functions
PTO self-correction?
The claimed invention in Ex parte Kubin, 83
USPQ2d 1410 (Bd. Pat. App. & Int. 2007), was an
isolated nucleic acid molecule. The claim stated that
the nucleic acid encoded a particular polypeptide.
The encoded polypeptide was identified in the claim
by its partially specified sequence, and by its ability
to bind to a specified protein.
A prior art patent to Valiante taught the polypeptide
. . . In view of Valiante's disclosure of the
polypeptide, and of routine prior art methods for
sequencing the polypeptide and isolating the nucleic
acid molecule, the Board found that a person of
ordinary skill in the art would have had a reasonable
expectation that a nucleic acid molecule within the
claimed scope could have been successfully obtained.
Remedies? Challenge Claims
Impermissible subject matter
Prior art
Insufficient description
Total patents:
74
Total claims:
1167
Total claims with problems: 448
Cumulative problems:
667
Patents on human genes: an analysis of scope and claims
Science 307:1566-7 (2005) Paradise, Andrews, Holbrook
Remedies? Challenge Scope
Public policy arguments to Congress
Mandatory licensing
Exclusion of diagnostic use
Changes would be prospective only
Statutory / constitutional arguments to courts
Natural phenomena, mental processes,
abstract ideas
Invalidation effective retrospectively
What’s Persuasive in court?
Drafter’s intent
Precedent (earlier cases)
Reasoning by analogy
Chemical moieties?
Plant extracts
I claim this substance
I can’t claim any substance w/
aromatic hydrocarbon
Alphabet?
I copyright an article
I can’t copyright a word
Assoc Molecular Pathology et al vs.
USPTO, Myriad Genetics et al
Not patentable subject matter
Naturally occurring genes
Association between mutation and disease
Contrary to constitutional enabling clause
Doesn’t promote progress of science
Contrary to first amendment protections
of freedom of thought, academic inquiry,
exchange of knowledge and ideas
5,747,282 Claims
1. An isolated DNA coding for a
BRCA1 polypeptide, said polypeptide
having the amino acid sequence set
forth in SEQ ID NO:2.
5. An isolated DNA having at least 15
nucleotides of the DNA of claim 1.
5,693,473 Claims
1. 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.
5,837,492 Claims
6. 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.
6,033,857 Claims
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.
5,710,001 Claims
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 gene 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.
5,747,282 Claims
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.