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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.
Measure (biomarker)

2.
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

Diagnostic Cos.

Clinical
Laboratories

Health Care
Providers

Patients

Pharma

Cos.

Commercial
Diagnostics


LDT

(Lab Developed Test
)

Research


ASR
(
Analyte

Specific
Reagent)


RUO

(Research Use
Only)

Development


IUO
(Investigational
Use Only test)

Research
Institutions

Payers

Patent Holders

FDA


Waived
(Class I novel device)


510(k) or “de novo”
(Class 2
device, market clearance)


PMA
(Class 3 device,

Pre
-
Market Approval)

Complex, evolving science

Complex, evolving, competitive industry

Complex, evolving regulatory environment

Complex, evolving economics

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



correlating

an elevated level of [biomarker] with
a deficiency of [vitamins].


Natural
Phenomenon?

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.


Exception analysis

1.
Laws of nature

2.
Physical phenomena

3.
Abstract ideas


Meaning?

Why?

Inherency?

Over
-
breadth?

Vague?

102

112, 1
st


112, 2
nd


“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.”

“… subject to the conditions
and requirements of this title.”

“[
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


over
-
breadth


abstract, vague

102

112, 2
nd


112, 1
st


Do we not trust
“the conditions and
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



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.


Transformative

Prometheus v. Mayo

Correlating

Pre
-
empt a Natural
Phenomenon?

Abstract
Idea?

Data
-

Gathering?

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
RNA from a human sample or



analyzing

a sequence of BRCA1
cDNA

made from
mRNA from said human sample ….



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 [BRCA
-
related] 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

Not

Transformative


determining

the level of [biomarker]
in said subject, …”

Transformative in
Prometheus
, even
without administering step

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.

Transformative

Does not pre
-
empt a
Natural Phenomenon

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 organism
-
associated
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
SMALL

things pass.


What is a
BIG

thing?


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




Moderator





















Andrew B.
Freistein



Lynn C. Tyler