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Ameritox, Ltd. v. Millennium Health, LLC

United States District Court, W.D. Wisconsin

February 19, 2015

AMERITOX, LTD., and MARSHFIELD CLINIC, INC., Plaintiffs,
v.
MILLENNIUM HEALTH, LLC., Defendant

Decided February 18, 2015.

Page 886

[Copyrighted Material Omitted]

Page 887

For Ameritox, Ltd., Plaintiff, Counter Defendant: James P Ulwick, LEAD ATTORNEY, Kramon and Graham PA, Baltimore, MD; Adam Louis Marchuk, PRO HAC VICE, Mark T. Smith, Matthew F. Carmody, Michael R. Osterhoff, Tiffany Patrice Cunningham, Timothy J. Carroll, Perkins Coie LLP, Chicago, IL; David Edwin Jones, Perkins Coie LLP, Madison, WI.

For Marshfield Clinic, Plaintiff: James P Ulwick, LEAD ATTORNEY, Kramon and Graham PA, Baltimore, MD; Naikang Tsao, LEAD ATTORNEY, Foley & Lardner LLP, Madison, WI; Adam Louis Marchuk, PRO HAC VICE, Matthew F. Carmody, Michael R. Osterhoff, Timothy J. Carroll, Perkins Coie LLP, Chicago, IL; David Edwin Jones, Perkins Coie LLP, Madison, WI; Kimberly Kristin Dodd, Foley & Lardner LLP, Milwaukee, WI; Matthew Brewer, Peter Benjamin Bensinger, Jr., PRO HAC VICE, Bartlit Beck Herman Palenchar & Scott, Chicago, IL.

For Millennium Health, LLC, Defendant: Robert Benjamin Wolinsky, LEAD ATTORNEY, Rebecca Cheryl Mandel, Steven P Hollman, Hogan Lovells U.S. LLP, Washington, DC; Arlene L Chow, PRO HAC VICE, Hogan Lovells U.S. LLP, New York, NY; Bonnie Chen, Hogan Lovells U.S. LLP, New York, NY; Douglas Maynard Poland, Jennifer Lynn Gregor, Godfrey & Kahn, S.C., Madison, WI.

For Millennium Health, LLC, Counter Claimant: Robert Benjamin Wolinsky, LEAD ATTORNEY, Steven P Hollman, Hogan Lovells U.S. LLP, Washington, DC; Arlene L Chow, PRO HAC VICE, Hogan Lovells U.S. LLP, New York, NY; Bonnie Chen, Bonnie Chen, Hogan Lovells U.S. LLP, New York, NY.

Page 888

OPINION AND ORDER

William M. Conley, United States District Judge.

This patent dispute presents a question of first impression with respect to the subject matter eligibility of a urine or other biological sample for drug screening and compliance protocols under 35 U.S.C. § 101, as well as related issues of enablement under § 112. The analysis is made more challenging by the state of flux in the treatment of competing goals inherent in § 101 challenges in recent years, and even in recent months. See Mayo Collaborative Services v. Prometheus Laboratories, Inc.,

Page 889

132 S.Ct. 1289, 182 L.Ed.2d 321 (2012); In re BRCA1- & BRCA2-Based Hereditary Cancer Test Patent Litig., 774 F.3d 755 (Fed. Cir. 2014); DDR Holdings, LLC v. Hotels.com, L.P., 773 F.3d 1245 (Fed. Cir. 2014); Ultramercial, Inc. v. Hulu, LLC, 772 F.3d 709 (Fed. Cir. 2014). Of course, this debate reflects a broader tension in patent law between what is legitimate invention in need of the incentives of patent law and what is merely description of the natural world for which no further incentive is required than our desire to understand it better -- a tension recognized virtually from the outset of the American patent system. See Le Roy v. Tatham, 55 U.S. 156, 159, 14 L.Ed. 367 (1852). Justice Breyer's relatively recent opinion in Mayo attempts to reconcile the goal of ensuring that patents do not " impede innovation more than it would tend to promote it," and the axiomatic notion that " all inventions, at some level embody, use, reflect, rest upon, or apply laws of nature, natural phenomena, or abstract ideas." Id. at 1293. Thus, Justice Breyer cautions that " too broad an interpretation of the exclusionary principle could eviscerate patent law." Id.

Here, plaintiffs Ameritox, Ltd., and Marshfield Clinic, LLC allege that defendant Millennium Health, LLC infringes two of their patents: U.S. Patents No. 7,585,680 (" the '680 patent" ), purporting to describe a method for drug screening and compliance protocols for one sample of urine from a patient on a prescribed medication regimen; and 7,785,895 (" the '895 patent" ), purporting to describe a similar method for one biological sample generally. ( See Am. Compl., Exs. A, B (dkt. ##106-1, 106-2).) Defendant Millennium seeks summary judgment of non-infringement and invalidity as to both patents. (Dkt. #126.) The parties also ask the court to construe various terms common to both patents, including most notably " known normative data" and " quantifying the concentration." (Def.'s Opening Br. (dkt #130); Pl.'s Opp'n (dkt. #172).) For the reasons that follow, the court will deny Millennium's motion for summary judgment of non-infringement and invalidity with respect to the '680 patent and grant the motion with respect to the '895 patent, finding the patent invalid for lack of enablement under § 112. For many of the same reasons, the court finds the '895 patent is vulnerable to the application of the exclusionary principle under § 101, while the '680 patent is substantially less so.

UNDISPUTED FACTS

I. The Licensing Agreement

Plaintiff Marshfield Clinic is a health care and research organization. Marshfield is also the assignee of the patents-in-suit from the inventors, Dr. Michael Larson and Dr. Thomas Richards.

Plaintiff Ameritox Ltd. is in the field of pain medication monitoring, including a provider of urine drug testing (" UDT" ) services. Ameritox is the exclusive licensee of the patents-in-suit pursuant to an exclusive license agreement between Ameritox and Marshfield dated March 15, 2010. In exchange for an exclusive license, Ameritox agreed to make certain royalty payments to Marshfield and to use good faith commercial efforts to develop, market, and sell a drug testing service based on the asserted patents.

II. The Testing Protocols

Ameritox tests urine samples on behalf of doctors, nurses, and other health-care providers who prescribe pain medications to treat chronic pain. (Am. Compl. (dkt. #106) ¶ 7.) Ameritox describes its UDT service as being able to " help clinicians assess whether patients are correctly taking medications and whether the prescription

Page 890

should be adjusted." (Dr. Paul J. Orsulak Infringement Report (" Orsulak Infringement Rept." ) (dkt. #117) ¶ 27.) Healthcare professionals periodically use Ameritox's services to monitor drug levels in their patients in order to help assess their patients' therapeutic response to medications and adherence to the treatment plan, as well as to detect aberrant behaviors ( e.g., illegal drug use) that may complicate treatment. ('680 patent at 2:17-20.)[1]

On May 16, 2011, Ameritox launched its current Rx Guardian CD service, which Ameritox asserts is based on the patents-in-suit.[2] The testing protocol for Rx Guardian CD has three phases. (Dr. Paul J. Orsulak Rebuttal Report (" Orsulak Rebuttal Rept." ) (dkt. #118) ¶ ¶ 246-56.) First, Ameritox performs a series of laboratory tests to detect and measure the amount of drug and drug metabolites in a patient's urine sample (the " detection" steps, which are reflected in steps (a)-(d) of the '680 patent). Second, Ameritox " normalizes" or " adjusts" urine drug levels for a patient's hydration status by determining the metabolite/creatinine ratio of the patient (the " normalization" step, as reflected in step (e) of the '680 patent).[3] Third, the Rx Guardian CD protocol compares a patient's normalized test results to a range of " normative data" collected from other clinical patients on the same medication, who Marshfield carefully monitored to insure adherence to their prescribed opioid regimen (the " determining" step, as reflected in step (f) of the '680 patent).

By comparing the patient's normalized value to a range of values for other clinical patients believed to be prescribed and taking the same medication properly, the health care provider can better assess whether a patient is likely to be taking the prescribed drug in a manner consistent with the prescribed regimen. The three steps outlined above largely truncate the steps outlined in claim 1 of the '680 patent, which states:

1. A method for quantifying at least one metabolite in a biological sample comprising the steps of:
(a) providing one biological sample obtained from a patient on a prescribed medication regimen, wherein the sample comprises at least one test metabolite, wherein in the sample is urine ;
(b) providing one set of known normative data specific to a reference metabolite, wherein the set of data is collected from a population that is on a prescribed medication regimen;

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(c) contacting the biological sample with an analytical device;
(d) detecting the presence of at least one test metabolite in the biological sample with the device, wherein the device is capable of measuring the concentration of the test metabolite in the sample;
(e) normalizing the biological sample to adjust for changes in the patient's hydration status by determining the metabolite/creatinine ratio of the patient; and
(f) quantifying the concentration of at least one test metabolite in the biological sample by comparing a ratio between the concentration of the test metabolite from the patient to the set of known normative data specific to the reference metabolite concentration.

( '680 patent at 21:9-32.)

III. The Specification, Prosecution History and Reexamination Certificates

The patents-in-suit have a priority date of August 28, 2003, and cover a method to monitor medication usage and to detect aberrant drug usage patterns, including over-use and under-use of prescribed medications. ('680 patent at ABSTRACT.) The patents share the same specification, which states that adherence to a prescribed medication regimen is important to the success of most treatments, " particularly in patients in drug abuse or chronic pain programs." ( Id. at 1:21-24.) The specification further describes a number of sources used by health care professionals to monitor medication usage, including interviews with patients, medical records, pill counts, prescription monitoring programs, and testing of biological samples, such as urine. ( Id. at 1:42-48, 15:11-15.) The specification also states that urine drug screens available in 2003 were limited to reporting a positive or negative result because of " the large amount of variability in urine drug concentrations, mostly due to variations in hydration and urinary output volume." ( Id. at 1:50-53.)

Both patents highlight problems with purely " up or down" test results. In particular, so long as patients took some amount of medication, their test results were positive and patients who overused or underused their medications continued to receive the same prescription:

To date, a test is purely negative or positive as to the presence or absence of a drug metabolite in the urine. Accordingly, it would be useful to develop a method to assess with confidence patient adherence to prescribed drug treatment regimens.

( Id. at 2:61-3:3 (emphasis added).) In light of the problems in the prior art, the specification goes on to state that:

[t]he method of the present invention enables improved clinical accuracy of protocols used in testing biological samples, such as, urine testing [and] the present invention can substantially improve the ability of a clinician to monitor and confirm whether a patient has been using the medication in a manner which is consistent with the prescription.

( Id. at 3:17-19, 4:50-54) (emphasis added).) The specification thus describes a method to " improve" or " enhance" medication monitoring and seeks to identify aberrant drug use. ( Id. at 3:17-19.)

The description of the invention is also reflected in the prosecution history, including the inventors' statement that:

Applicants developed a normative database for the drug metabolite hydration corrected ratio that allows statistical analysis of drug metabolite level in urine to determine if the medication is utilized in a manner consistent with the prescription or what the potential dose may have been.

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(Declaration of Rebecca C. Mandel (" Mandel Decl." ), Ex. 24 (dkt. #129-24) pp.14-15); see also id., Ex. 17 (dkt. #129-17) p.9.) By contrasting the invention with prior art references, the invention is better elucidated. For example, the inventors submitted to the Patent Office that the " Kell [reference] focuses on adulteration of the urine sample, whereas applicants' method [a] focuses on identification of the urine, [b] correction of hydration in order to reduce variability and then [c] comparison of that corrected drug metabolite to a normative database to identify appropriate or inappropriate" drug use. ( Id., Ex. 24 (dkt. #129-24) p.15.) The inventors further represents that " none of the patent publications from the Kell portfolio anticipate or render the claims obvious." ( Id.)

The Patent Office agreed with the inventors' submission leading to issuance of both patents. The patents also survived two more recent reexaminations, with the Patent Office issuing: the first reexamination certificates for the patents-in-suit in May and June 2013, leaving each of the challenged claims intact and issuing additional claims, and a second set of reexamination certificates on May and July 2014 -- again leaving each of the challenged claims intact. ( See id., Ex. 1 (dkt. #129-1) pp.27-30; id., Ex. 2 (dkt. #129-2) pp.26-29.)

IV. Prior Art[4]

There are several references cited in the prosecution history (and by the parties themselves) that constitute prior art so well known by the " scientific community" at the time of the invention that it assists in determining whether the combination of elements in '680 patent constitute inventive concept. See Mayo, 132 S.Ct. at 1298 (patent is invalid if any additional steps consist of well-understood, routine, conventional activity already engaged in by the scientific community). In reviewing these references, the court is mindful that when prior art is put into evidence -- either existing as part of the prosecution history or cited in expert reports -- the reference must be considered in its entirety, i.e., as a whole, including portions that would teach or steer away from the claimed invention. W.L. Gore & Assocs., Inc. v. Garlock, Inc., 721 F.2d 1540, 1550 (Fed. Cir. 1983).

One of the most relevant prior art references in this case is the George Article. S. George & R.A. Braithwaite, A Pilot Study to Determine the Usefulness of the Urinary Excretion of Methadone and its Primary Metabolite (EDDP) as Potential Markers of Compliance in Methadone Detoxification Programs, J. Analytical Toxicol., Mar./Apr. 1999, at 81-85. ( See Mandel Decl., Ex. 43 (dkt. #129-43).) The authors of the George Article investigate urinary excretion to determine whether " methadone or EDDP could be a simple and noninvasive marker of methadone compliance." ( Id. at 83.) Testing was specifically performed " to try to resolve the issue of whether urinary excretion could be used in place of plasma concentration as a mechanism to monitor compliance during methadone replacement therapy for opiate addiction." ( Id. (emphasis added).)

The George Article was cited before the Patent Office, and it is also cited at length in Dr. Wu's expert report, opining that the patents were invalid on § § 101, 102 and

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103 grounds.[5] Millennium further cites the George Article in support of the factual proposition that " normalizing urinary samples via metabolite/creatinine ratios [was] a routine and conventional practice" at the time of the invention. (Def.'s PFOFs (dkt. #127) ¶ 259.) The crux of the article, however, is best summarized by Ameritox's expert Dr. Orsulak who explains:

One aim of the George article was to determine if quantitative urinary excretion data of methadone and EDDP may be used to distinguish between compliant and noncompliant subjects undergoing methadone detoxification. (George article at 83.) The George article discloses two datasets from different patient populations. One patient population consisted of 14 control subjects. A second patient population consisted of 56 drug abusers, including those suspected of missing dosages or topping up from other sources of methadone. (George article at 83.) The George article concludes, " there is too large of an interindividual variation to use urinary excretion concentrations of methadone or EDDP as markers of compliance." (George article at 83.)

( Orsulak Rebuttal Rept. (dkt. #118) ¶ 59.)

As Dr. Orsulak points out, the George Article " never compares the results from any of the 56 drug abusers to the 14 control subjects. Rather, to the extent any comparison is made, the George article only discloses comparing a patient's test result to earlier results from that same patient." ( Id. at ¶ 86 (emphasis added).) " In other words, the George article discloses a straight historical results analysis, without any 95% inclusion range being involved, nor is any comparison to a known normative database disclosed." ( Id.) Thus, the " only comparison disclosed in the George article is a single patient's test result to his/her own earlier test results." ( Id.) These facts were not squarely controverted in Dr. Wu's opinion, nor is there anything else in the record that puts them into dispute. The George Article offers further insights into what was well known at the time of the claimed invention:

o " there is too large of an interindividual variation to use urinary excretion concentrations of methadone or EDDP as markers of compliance" ;
o urinary excretion testing " would point to a lack of suitability of using urine concentrations of EDDP or methadone as markers of compliance" ; and
o " the only reliable method available to monitor methadone compliance is the use of plasma methadone drug testing."

( Mandel Decl., Ex. 43 (dkt # 129-43) 84-85.) In each respect, the George Article supports a conclusion that at the time of the invention, blood testing was the only reliable method to determine whether a patient was complying with a prescribed drug regimen.

Another article that reflects the state of the art is the Haddow Article. Haddow, J., et al., Replacing Creatinine Measurements with Specific Gravity Values to Adjust Urine Cotinine Concentrations, CLINICAL CHEM. 562 (1994). ( See Expert Report of Roger L. Bertholf, Ph.D. (" Bertholf Rept." ), Ex. H (dkt. #209-8).) The Haddow Article evaluates the use of creatinine and specific gravity values in a study of environmental tobacco smoke exposure in non-smoking children with asthma. ( Id. at 562.) Haddow uses a regression analysis

Page 894

of the logarithm of urinary cotinine and creatinine in a population of 116 children who were not exposed to environmental tobacco smoke. ( Id.)

" [A]lthough measuring creatinine measurements to reflect hydration" was known, Haddow teaches that it adds " complexity and cost when such measurements are applied in routine and clinical practice." ( Id.) This is why " specific gravity (relative density) measurements in urine samples from children with asthma" were used to " provide information equivalent to that from creatinine measurements." ( Id.) Moreover, Haddow does not involve drug treatment or compliance with a prescribed drug regimen and no known normative database is developed. ( Id. at 562-64.)

V. The Skilled Addressee[6]

For the purposes of identifying a person of ordinary skill in the art, the court agrees with Dr. Orsulak that the " relevant art of the subject matter claimed by the patents-in-suit is medication or therapeutic drug monitoring." (Orsulak Rebuttal Rept. (dkt. #118) ¶ 3.) Orsulak further opines that such a person would have a degree in a field " such as medicine, biochemistry, biology, clinical health psychology, clinical laboratory sciences, clinical toxicology, or pharmacology and several years of work experience related to medication or therapeutic drug monitoring, including drugs-of-abuse testing or substance abuse testing." ( Id.) This characterization of the skilled addressee seems sensible; nothing in Millennium's materials alters this viewpoint; and the characterization is consistent with the field of the art applicable to the invention.[7]

VI. The Claims of the '680 and the '895 patent

The disputed claims in suit -- specifically claims 1, 2, 4-7, 10 and 16-18 of the '680 patent and claims 1, 4-5, 10-12 and 14 of the '895 patent -- generally disclose a series of six steps that culminate in a final comparison step between the drug collected from a patient's urine sample to " known normative data" collected from a patient population. Neither party disagrees with this characterization. As such, the asserted independent claims of the '680 patent (claims 1 and 4) and the '895 patent are represented below.

Claim 1 of the '680 patent states:

1. A method for quantifying at least one metabolite in a biological sample comprising the steps of:
(a) providing one biological sample obtained from a patient on a prescribed medication regimen, wherein the sample comprises at least one test metabolite, wherein in the sample is urine;
(b) providing one set of known normative data specific to a reference metabolite, wherein the set of data is collected from a population that is on a prescribed medication regimen;
(c) contacting the biological sample with an analytical device;
(d) detecting the presence of at least one test metabolite in the biological sample with the device, wherein the device is capable of measuring the concentration of the test metabolite in the sample;

Page 895

(e) normalizing the biological sample to adjust for changes in the patient's hydration status by determining the metabolite/creatinine ratio of the patient; and
(f) quantifying the concentration of at least one test metabolite in the biological sample by comparing a ratio between the concentration of the test metabolite from the patient to the set of known normative data specific to the reference metabolite concentration.

( '680 patent at 21:9-32 (terms in dispute have been bolded).)

Claim 1 of the '895 patent states:

A method for quantifying at least one metabolite in at least one biological sample comprising the steps of:

(a) providing at least one biological sample obtained from a patient on a prescribed medication regimen, wherein the biological sample comprises at least one test metabolite;
(b) providing one set of known normative data specific to a reference metabolite, wherein the set of data is collected from a population that is on a prescribed medication regimen;
(c) contacting the biological sample with an analytical device;
(d) detecting the presence of at least one test metabolite in the biological sample with the device, wherein the device is capable of measuring the concentration of the test metabolite in the at least one biological sample;
(e) normalizing the biological sample to adjust for changes in the patient's hydration status by determining the metabolite/creatinine ratio of the patient; and
(f) quantifying the concentration of at least one test metabolite in the biological sample by comparing a ratio between the concentration of the test metabolite from the patient to the set of known normative data specific to the reference metabolite concentration.

( '895 patent at 20:56-21:12.)

With regard to the disputed terms, the parties' preferred constructions are summarized in the following table:

Disputed Terms

Plaintiff

Defendant

Ameritox's

Millennium's

Preferred

Preferred

Construction

Construction

" known normative data"

Plain and Ordinary

Known dose-specific data that is

(all asserted claims)

Meaning

related to the population it is

intended to predict

" quantifying the

Plain and Ordinary

To the extent that this term can be

concentration of at

Meaning

construed, it means: predicting the

least one test

dosage taken by a patient from at

metabolite in the

least one test metabolite in the

biological sample by

biological sample by comparing the

comparing a ratio

ratio based on the concentration of

between the

the test metabolite from the patient

concentration of the

to the set of known normative data

test metabolite from

specific to the reference metabolite

the patient to the set

concentration

of known normative

data specific to the

reference metabolite

concentration"

(all asserted claims)

Millennium contends that the purpose of the patents is to quantify a specific dose. It argues that this purpose provides the proper context and is dispositive of what is meant by " known normative data." Similarly, with respect to the second disputed phrase -- " quantifying the concentration" --

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Millennium argues in favor of a definition that specifically predicts the dosage of the test metabolite. Ameritox contends that neither of these disputed terms should be so confined. More specifically, Ameritox argues that Millennium's construction seeks to import limitations from the specification to deviate from the plain and ordinary meaning of the claim terms.

OPINION

Analysis of patent infringement is a two-step process: " first, the scope of the claims are determined as a matter of law, and second, the properly construed claims are compared to the allegedly infringing device to determine, as a matter of fact, whether all of the limitations of at least one claim are present, either literally or by a substantial equivalent, in the accused device." Teleflex, Inc. v. Ficosa N. Am. Corp., 299 F.3d 1313, 1323 (Fed. Cir. ...


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