THE CLEVELAND CLINIC FOUNDATION, CLEVELAND HEARTLAB, INC., Plaintiffs-Appellants
TRUE HEALTH DIAGNOSTICS LLC, Defendant-Appellee
from the United States District Court for the Northern
District of Ohio in No. 1:15-cv-02331-PAG, Judge Patricia A.
Lawrence D. Rosenberg, Jones Day, Washington, DC, argued for
plaintiffs-appellants. Also represented by Susan M. Gerber,
Louis Marchuk, Perkins Coie LLP, Chicago, IL, argued for
defendant-appellee. Also represented by Michael Robert
Osterhoff, Mark T. Smith, Caroline Ayres Teichner; Dan L.
Bagatell, Hanover, NH.
Lourie, Reyna, and Wallach, Circuit Judges.
Cleveland Clinic Foundation and Cleveland Heartlab, Inc.
accused True Health Diagnostics LLC of infringement of three
patents that claim methods for testing for myeloperoxidase in
a bodily sample and a fourth patent that claims a method for
treating a patient that has cardiovascular disease. The
United States District Court for the Northern District of
Ohio found that the asserted claims of the three testing
patents are not directed to patent-eligible subject matter
and that Cleveland Clinic failed to state a claim of
contributory or induced infringement of the fourth patent.
For the reasons explained below, we affirm.
2003, researchers at the Cleveland Clinic Foundation
developed methods for detecting the risk of cardiovascular
disease in a patient. When an artery is damaged or inflamed,
the body releases the enzyme myeloperoxi-dase, or MPO, in
response. MPO is an early symptom of cardiovascular disease,
and it can thus serve as an indicator of a patient's risk
of cardiovascular disease.
prior art taught that MPO could be detected in an
atherosclerotic plaque or lesion that required a surgically
invasive method. Another prior art method indirectly
detected for MPO in blood. Yet another known method could
detect MPO in blood but yielded results that were not
predictive of cardiovascular disease. The inventors here
purportedly discovered how to "see" MPO in blood
and correlate that to the risk of cardiovascular disease.
patents disclose methods for detecting MPO and correlating
the results to cardiovascular risk. The pa- tents disclose that
"[m]yeloperoxidase activity may be determined by any of
a variety of standard methods known in the art."
E.g., J.A. 39 at col. 8 ll. 32-33. These methods
include colorimetric-based assay, flow cytometry, and
enzyme-linked immunosorbent assay ("ELISA").
Additionally, the patents disclose MPO detection kits
modified from commercially available kits "by including,
for example, different cut-offs, different sensitivities at
particular cut-offs, as well as instructions or other printed
material for characterizing risk based upon the outcome of
the assay." E.g., J.A. 38 at col. 6 ll. 21-24.
addition to ways to "see" MPO, the inventors
developed a way to correlate MPO with risk of developing
cardiovascular disease. To do this, the inventors compiled
MPO data from a population to create a
"predetermined" or "control" value. Then,
using statistical methods, the inventors analyzed the data
based on whether the person was "apparently
healthy" or had some cardiovascular disease.
E.g., J.A. 45 at col. 20 ll. 32-43. Diagnosers could
then use this data to determine whether a patient presents a
risk of cardiovascular disease:
If the level of the present risk predictor in the test
subject's bodily sample is greater than the predetermined
value or range of predetermined values, the test subject is
at greater risk of developing or having [cardiovascular
disease] than individuals with levels comparable to or below
the predetermined value or predetermined range of values.
J.A. 46 at col. 21 ll. 37-42.
'552 patent claims methods for characterizing a test
subject's risk for cardiovascular disease by determining
levels of MPO in a bodily sample and comparing that with the
MPO levels in persons not having cardiovascular disease. The
dependent claims limit the way MPO is detected and how the
MPO values in the control subjects are evaluated. The
district court analyzed claims 11, 14, and 15, which provide:
11. A method of assessing a test subject's risk of having
atherosclerotic cardiovascular disease, comprising
comparing levels of myeloperoxidase in a bodily sample from
the test subject with levels of myeloperoxidase in comparable
bodily samples from control subjects diagnosed as not having
the disease, said bodily sample being blood, serum, plasma,
blood leukocytes selected from the group consisting of
neutrophils, monocytes, sub-populations of neutrophils, and
sub-populations of monocytes, or any combination thereo[f];
wherein the levels of myeloperoxidase in the bodily from the
test subject relative to the levels of [m]yeloperoxidase in
the comparable bodily samples from control subjects is
indicative of the extent of the test subject's risk of
having atherosclerotic cardiovascular disease.
J.A. 50 at col. 30 ll. 48-62.
14. A method of assessing a test subject's risk of
developing a complication of atherosclerotic cardiovascular
determining levels of myeloperoxidase (MPO) activity,
myeloperoxidase (MPO) mass, or both in a bodily sample of the
test subject, said bodily sample being blood, serum, plasma,
blood leukocytes selected from the group consisting of
neutrophils and monocytes, or any combination thereof;
wherein elevated levels of MPO activity or MPO mass or both
in the test subject's bodily sample as compared to levels
of MPO activity, MPO mass, or both, respectively in
comparable bodily samples obtained from control subjects
diagnosed as not having the disease indicates that the test
subject is at risk of developing a complication of
atherosclerotic cardiovascular disease.
J.A. 51 at col. 31 ll. 8-23.
15. The method of claim 14, wherein the test subject's
risk of developing a complication of atherosclerotic
cardiovascular disease is determined by comparing levels of
my[elo]peroxidase mass in the test subject's bodily
sample to levels of myelop-eroxidase mass in comparable
samples obtained from the control subjects.
J.A. 51 at col. 31 ll. 24-29.
'286 patent and '581 patent further claim ways of
detecting MPO. The dependent claims of the '286 patent
limit MPO detection by flow cytometry and further require
detection of another compound, troponin. Other dependent
claims of the '286 patent and '581 patent require
detection of MPO byproducts. The district court analyzed
claims 21 and 22 of the '286 patent and claim 5 of the
'581 patent, which provide:
21. A method of assessing the risk of requiring medical
intervention in a patient who is presenting with chest pain,
characterizing the levels of myeloperoxidase activity,
myeloperoxidase mass, or both, respectively in the bodily
sample from the human patient, where-in said bodily sample is
blood or a blood derivative,
wherein a patient whose levels of myeloperoxidase activity,
myeloperoxidase mass, or both is characterized as being
elevated in comparison to levels of myeloperoxidase activity,
myeloperoxidase mass or both in a comparable bodily samples
obtained from individuals in a control population is at risk
of requiring medical intervention to prevent the occurrence
of an adverse cardiac event within the next six months.
J.A. 71 at col. 23 l. 45-col. 24 l. 10.
22. A method of determining whether a patient who presents
with chest pain is at risk of requiring medical intervention
to prevent an adverse cardiac event ...