Cleveland Clinic Found. v. True Health Diagnostics LLC

• Decision Date: 16 June 2017
• Docket Number: 2016-1766
• Citation: 859 F.3d 1352
• Parties: The CLEVELAND CLINIC FOUNDATION, Cleveland Heartlab, Inc., Plaintiffs–Appellants v. TRUE HEALTH DIAGNOSTICS LLC, Defendant–Appellee
• Court: U.S. Court of Appeals — Federal Circuit

859 F.3d 1352

The CLEVELAND CLINIC FOUNDATION, Cleveland Heartlab, Inc., Plaintiffs–Appellants

v.TRUE HEALTH DIAGNOSTICS LLC, Defendant–Appellee

2016-1766

United States Court of Appeals, Federal Circuit.

Decided: June 16, 2017

Lawrence D. Rosenberg , Jones Day, Washington, DC, argued for plaintiffs-appellants. Also represented by Susan M. Gerber , Cleveland, OH.

Adam 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.

Before Lourie, Reyna, and Wallach, Circuit Judges.

Reyna, Circuit Judge.

The 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.

BACKGROUND

In 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 myeloperoxidase, 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.

The 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.

The patents disclose methods for detecting MPO and correlating the results to cardiovascular risk.¹ The patents 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.

In 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.

The '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 disease comprising:

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 myeloperoxidase mass in comparable samples obtained from the control subjects.

J.A. 51 at col. 31 ll. 24–29.

The '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, comprisingcharacterizing the levels of myeloperoxidase activity, myeloperoxidase mass, or both, respectively in the bodily sample from the human patient, wherein 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 within the next six months comprising:

comparing the level of a risk predictor in a bodily sample from the subject with a value that is based on the level of said risk predictor in comparable samples from a control population, wherein said risk predictor is myeloperoxidase activity, myeloperoxidase mass, a myeloperoxidase-generated oxidation product, or any combination thereof, and wherein said bodily sample is blood, serum, plasma, or urine,

wherein a subject whose bodily sample contains elevated levels of said risk predictor as compared to the control value is at risk of requiring medical intervention to prevent an adverse cardiac event within 6 months of presenting with chest pain, and

wherein the difference between the level of the risk predictor in the patient's bodily sample and the level of the risk predictor in a comparable bodily sample from the control population establishes the extent of the risk to the subject of requiring medical intervention to prevent an adverse cardiac event within the next six months.

J.A. 71 at col. 24 ll. 11–33.

5. 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 within the next six months comprising:

determining the level of risk predictor in a bodily sample from the subject, wherein said risk predictor is myeloperoxidase activity, myeloperoxidase mass, a myeloperoxidase (MPO)-generated oxidation product or any combination thereof,

wherein said bodily sample is blood, serum, plasma or urine,

wherein said myeloperoxidase-generated oxidation product is nitrotyrosine or a myeloperoxidase-generated lipid peroxidation product selected from [list of products] or any combination thereof, and

comparing the level of said risk predictor in the bodily sample of the patient to the level of said risk predictor in comparable samples obtained from a control population,

wherein a subject whose bodily sample contains elevated levels of said risk predictor as compared to the control value is at risk of requiring medical intervention to prevent an adverse cardiac event within 6 months of presenting with chest pain.

J.A. 86 at col. 20 ll. 12–50.

The '260 patent builds on these patents and requires administration of a lipid lowering drug to a patient at risk of cardiovascular disease. Claim 1 of the '260 patent recites:

1. A method for administering a lipid lowering agent to a human patient based on elevated levels of myeloperoxidase (MPO) mass and/or

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