Transcript Claiming Medical Methods: Between Madness and Too Much Ado

Patenting Challenges for Diagnostic
Methods: Patent Eligibility;
Divided Infringement
October 20, 2011
AIPLA Annual Meeting
Washington, D.C.
James J. Kelley
Senior Director – Assistant General Patent Counsel
Eli Lilly and Company
Indianapolis, Indiana
The contents of this presentation represent the views of the author and do not
represent the policies, viewpoints, or business of Lilly or its management.
Diagnostics
• Diagnosis = correlating a measurement with a
medical conclusion
1.
2.
Measure (biomarker)
Correlate presence, absence, or amount of biomarker with
safety, effectiveness, dose, etc. of pharmaceutical
treatment
– high fasting blood glucose  diabetes
– high blood pressure  risk of stroke, heart disease
• Lilly is not a diagnostics company
– But Lilly’s products are becoming “tied” to diagnostics
Value of Diagnostics
• “Diagnostic tests are estimated to influence 60
to 70 percent of all treatment decisions, yet
account for only 5 percent of hospital costs
and 2 percent of Medicare expenditures.”
– McKinsey Quarterly, February 2010, The
Microeconomics of Personalized Medicine
Personalized Medicine
• Right drug, right patient, right dose, right time
• Who is the “right patient?” What is the “right drug
and dose?” When is best?
– Genetics & proteomics & bioinformatics: “Disruptive
technologies” – disrupting medicine
– Dividing disease categories into smaller categories
• “diabetes” “diabetes in patients with a particular genetic
variation”
• “Companion Diagnostics”
– Drug labeling says “test for biomarker.”
– Diagnostic labeling says “to be used with drug.”
Examples
• Insulin & glucose and hemoglobinA1c (HbA1c)
– “right dose” of insulin for a patient with diabetes
• HERCEPTIN® & Hercep-Test™
– “right patient” = one with breast cancer cells having high
level of HER2 protein
– Genentech, Dako (1998)
• ZELBORAF™ & cobas® 4800 BRAF V600 Mutation Test
– “right patient” = one with melanoma & particular mutated
protein
– Roche, Roche (2011)
• XALKORI® & Vysis ALK Break Apart FISH Probe Kit
– “right patient” = one with late-stage lung cancer &
particular mutant protein
– Pfizer, Abbott (2011)
Complexity
Pharma Cos.
Research
Institutions
Research
ASR (Analyte Specific
Reagent)
Payers
Patients
Health Care
Providers
Diagnostic Cos.
Clinical
Laboratories
Commercial Diagnostics
LDT (Lab Developed Test)
Development
IUO (Investigational
Use Only test)
RUO (Research Use Only)
Complex, evolving science
Complex, evolving, competitive industry
Complex, evolving regulatory environment
Complex, evolving economics
Waived (Class I novel device)
FDA
Patent Holders
510(k) or “de novo” (Class 2
device, market clearance)
PMA (Class 3 device,
Pre-Market Approval)
Patent Uncertainty
• Are diagnostic correlations patent-eligible?
Should they be?
– Natural phenomona?
– Abstract ideas?
• Divided infringement
– Multiple actors
35 U.S.C. 101 Inventions patentable.
• Whoever invents or discovers any new and
useful process, …, may obtain a patent
therefor, subject to the conditions and
requirements of this title.
LabCorp v. Metabolite
• 13. A method for detecting a deficiency of
[particular vitamins] in warm-blooded
animals comprising the steps of:
– assaying a body fluid for an elevated level of [a
particular biomarker]; and
Natural
– correlating an elevated
level of [biomarker] with
a deficiency Phenomenon?
of [vitamins].
Justice Breyer, Dissenting from DIG
(2006)
“[T]he category of non-patentable
‘phenomena of nature,’ like the categories of
‘mental processes,’ and ‘abstract intellectual
concepts,’ is not easy to define.”
“There can be little doubt that the correlation
between homocysteine and vitamin deficiency
set forth in claim 13 is a ‘natural
phenomenon.’”
– LabCorp v. Metabolite
Justice Frankfurter (1948)
• “It only confuses the issue, however, to introduce
such terms as ‘the work of nature’ and the ‘laws
of nature.’ For these are vague and malleable
terms infected with too much ambiguity and
equivocation. Everything that happens may be
deemed ‘the work of nature,’…. Arguments
drawn from such terms for ascertaining
patentability could fairly be employed to
challenge almost every patent.”
– Funk Bros. v. Kalo (concurring)
• Still ambiguous and confusing today.
Bilski
• Machine-or-transformation test is not the
exclusive test; only a clue. “… subject to the conditions
and requirements of this title.”
• Exception analysis
1. Laws of nature
Inherency?
102
Meaning?
st
2. Physical phenomena
Over-breadth?
112,
1
Why?
3. Abstract ideas
Vague?
112, 2nd
“The concepts covered by these exceptions are
‘part of the storehouse of knowledge of all men …
free to all men and reserved exclusively to none.’”
Bilski, quoting Funk Bros.
Deemed “reserved to the public.”
“[Flook’s process was] unpatentable under §
101, … because once that algorithm [wa]s
assumed to be within the prior art, the
application, considered as a whole,
contain[ed] no patentable invention.” Bilski
AIA § 14 TAX STRATEGIES DEEMED WITHIN THE PRIOR ART.
Ariad v. Lilly
80. [A method for modifying effects of external
influences on a eukaryotic cell, which external influences
induce NF-κB-mediated intracellular signaling, the
method comprising altering NF-κB activity in the cells
such that NF-κB-mediated effects of external influences
are modified, wherein NF-κB activity in the cell is
reduced] wherein reducing NF-κB activity comprises
reducing binding of NF-κB to NF-κB recognition sites on
genes which are transcriptionally regulated by NF-κB.
• Inherently anticipated 102
Do we not trust
• over-breadth 112, 1st
“the conditions and
• abstract, vague 112, 2nd
requirements of
this title?”
Prometheus v. Mayo
A method of optimizing therapeutic
efficacy for treatment of [condition X]…,
comprising:
– (a) administering a [particular] drug …
to a subject; and
– (b) determining the level of [biomarker]
in said subject,
– wherein the level of [biomarker] less than
about 230 … indicates a need to increase the
amount of said drug subsequently
administered to said subject and
– wherein the level of [biomarker] greater than
about 400 … indicates a need to decrease the
amount of said drug subsequently
administered to said subject.
The particular drug is converted to another compound in the body. This “metabolite” is the biomarker.
Prometheus v. Mayo
1. Machine or transformation test
2. Exception analysis
Prometheus v. Mayo
A method of optimizing therapeutic
efficacy for treatment of [condition X]…,
comprising:
– (a) administering a [particular] drug …
to a subject; and
– (b) determining the level of [biomarker]
in said subject,
DataTransformative
Gathering?
– wherein the level of [biomarker] less than
about 230 … indicates a need to increase the
amount of said drug subsequently
administered to said subject and
– wherein the level of [biomarker] greater than
about 400 … indicates a need to decrease the
amount of said drug subsequently
administered to said subject.
Pre-empt a Natural
Phenomenon?
Abstract
Correlating
Idea?
The particular drug is converted to another compound in the body. This “metabolite” is the biomarker.
Prometheus v. Mayo
• The correlating “step” involves a natural
phenomenon …
– The court did not define what natural phenomenon it
was talking about.
– Holds that the claim does not pre-empt all uses of a
natural phenomenon (whatever it is).
• The correlating “step” is an abstract idea/mental
step …
– But the preceding steps are not merely extra-solution
“data-gathering” steps – they are the purpose.
– Holds that the claim is not ineligible for being
abstract.
Issue Presented – Mayo v. Prometheus
“This case concerns whether a patentee can
monopolize basic, natural biological relationships.
The Court has twice granted certiorari on the question
presented, without yet resolving the issue [this case
and LabCorp].
“The question presented is: Whether 35 U.S.C. § 101 is
satisfied by a patent claim that covers observed
correlations between blood test results and patient
health, so that the claim effectively preempts all uses
of the naturally occurring correlations, simply because
well-known methods used to administer prescription
drugs and test blood may involve ‘transformations’ of
body chemistry.”
– http://www.supremecourt.gov/qp/10-01150qp.pdf
Myriad
1. A method for detecting [certain] germline
alteration[s] in a BRCA1 gene … in a human which
comprises
–
analyzing a sequence
of a BRCA1
gene or BRCA1
“determining
the level
of [biomarker]
RNA from a human sample or
in said subject, …”
–
analyzing a sequence
of BRCA1 cDNA made
Transformative
in Prometheus,
evenfrom
mRNA from said human sample ….
without administering step
Not
Transformative
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 [BRCA-related] first sequence … from
said tumor sample, … with a second [BRCArelated] sequence … from a nontumor sample of
said subject …,
– wherein a difference in the sequence[s] …
indicates a somatic alteration in the BRCA1 gene in
said tumor sample.
Not
Transformative
Myriad
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.
Does not pre-empt a
Natural Phenomenon
Transformative
Classen
1. A method of immunizing a mammalian subject which comprises:
(I) screening a plurality of immunization schedules, by
–
identifying a first group of mammals and at least a second group of mammals, said mammals
being of the same species, the first group of mammals having been immunized with one or
more doses of one or more infectious disease-causing organism-associated immunogens
according to a first screened immunization schedule, and the second group of mammals
having been immunized with one or more doses of one or more infectious disease-causing
organism-associated immunogens according to a second screened immunization schedule,
each group of mammals having been immunized according to a different immunization
schedule, and
– comparing the effectiveness of said first and second screened immunization schedules in
protecting against or inducing a chronic immune-mediated disorder in said first and second
groups, as a result of which one of said screened immunization schedules may be identified as
a lower risk screened immunization schedule and the other of said screened schedules as a
higher risk screened immunization schedule with regard to the risk of developing said chronic
immune mediated disorder(s),
(II) immunizing said subject according to a subject immunization schedule,
according to which at least one of said infectious disease-causing organismassociated immunogens of said lower risk schedule is administered in accordance
with said lower risk screened immunization schedule, which administration is
associated with a lower risk of development of said chronic immune-mediated
disorder(s) than when said immunogen was administered according to said higher
risk screened immunization schedule.
Transformative
Classen
1. A method of determining whether an
immunization schedule affects the
incidence or severity of a chronic
immune-mediated disorder in a treatment
group of mammals, relative to a control
group of mammals, which comprises
immunizing mammals in the treatment
group of mammals with one or more
doses of one or more immunogens,
according to said immunization schedule,
and comparing the incidence, prevalence,
frequency or severity of said chronic
immune-mediated disorder or the level of
a marker of such a disorder, in the
treatment group, with that in the control
group.
Not
Transformative
“A Coarse Filter”
Removes
BIG things and lets
What is a
BIG thing?
–
–
–
–
SMALL
things pass.
Correlation between force and (mass and distance)?
Correlation between mass and energy?
All means of telegraphy?
A basic algorithm in computer technology?
BIG or
?
SMALL
• Correlation between a particular biomarker
and a particular vitamin deficiency?
• Correlation between the level of metabolites
of a particular drug and its safety?
• Correlation between a genetic variation and
effectiveness of a particular drug?
• Correlation between having any 3 out of 25
genetic markers and long-term survival while
on a particular class of cancer drugs?
Meanwhile, . . . .
• How do you write a claim that will be eligible?
• Claim-drafting ingenuity?
– To “evade” eligibility limitations?
– Add a “transformative” step or steps?
Eligibility Evasions and
Restrictions Decried
“[E]ligibility restrictions usually engender a
healthy dose of claim-drafting ingenuity. In
almost every instance, patent claim drafters
devise new claim forms and language that
evade the subject matter exclusions. …
Excluding categories of subject matter from
the patent system achieves no substantive
improvement in the patent landscape.”
Classen v. Biogen IDEC, RADER, Chief Judge, additional views, joined by
PAULINE NEWMAN, Circuit Judge, August 31, 2011, 3-4.
Divided Infringement
• BMC (2007) (“joint liability may be found when
one party ‘control[s] or direct[s]’ the activities of
another party.”)
• Akamai (2010) (“as a matter of Federal Circuit law
there can only be joint infringement when there
is an agency relationship between the parties
who perform the method steps or when one
party is contractually obligated to the other to
perform the steps.”)
• McKesson (2011)
• Concern about contracting away liability.
Diagnostics Actors
•
•
•
•
•
Patients
Health care providers – docs, hospitals, clinics
Clinical Laboratories
Diagnostic Cos.
Pharma Cos.
Ingenuity Encouraged
“The concerns over a party avoiding
infringement by arms-length cooperation can
usually be offset by proper claim drafting. A
patentee can usually structure a claim to
capture infringement by a single party.”
– BMC Resources Inc. v. Paymentech LP, 498 F.3d
1373, 1381 (Fed. Cir. 2007).
En Banc Questions
“If separate entities each perform separate steps of a
method claim, under what circumstances would that claim
be directly infringed and to what extent would each of the
parties be liable?”
Akamai Technologies, Inc. v. Limelight Networks, Inc.
“1. If separate entities each perform separate steps of a
method claim, under what circumstances, if any, would
either entity or any third party be liable for inducing
infringement or for contributory infringement? []
“2. Does the nature of the relationship between the
relevant actors—e.g., service provider/user;
doctor/patient—affect the question of direct or indirect
infringement liability?”
McKesson Technologies, Inc. v. Epic Systems, Corp.
AIPLA Position
• “Whoever” in § 271(a) is singular or plural
– 1 U.S.C. §1, ¶ 2 (“words importing the singular include
and apply to several persons, parties, or things.”)
– Dictionary (“whatever person or persons”)
– “Whoever” in §101 (“whoever invents”) may be
singular or plural (§116 Joint inventors).
• Joint Tortfeasor “3-step”
1. All elements conducted by one or some?
2. Who (all) caused harm?
3. Who’s participation was substantial enough for
liability?
Summary
• Key eligibility and divided infringement cases are
at Supreme Court and Federal Circuit (en banc).
– Potentially
BIG impact on diagnostics patenting.
• Follow fundamental claim-drafting principles:
–
–
–
–
minimize # of steps
single entity carrying out all steps, if possible
transformative gerunds
explain transformative gerunds in specification
THANK YOU!
Sponsors
Program Coordinator –
Andrew B. Freistein
Moderator –
Lynn C. Tyler