Courts Invalidating Life Sciences Discoveries at Alarming Rate Under Mayo/Alice

In the 1980s, Dr. Malcolm Simons discovered that certain DNA sequences in coding regions (exons) of genes are correlated with non-coding regions (in-trons), i.e., they are "linked" together within an individual's genome. These non-coding regions, often colloquially referred to as "junk DNA," were at that time believed not to serve any relevant biological function. Using this discovery, Dr. Simons and other scientists were able to devise methods using the junk DNA to detect alleles of particular genes and use that information to ultimately diagnose and treat genetic disorders.¹

In the 1990s, Drs. Dennis Lo and James Wainscoat discovered that cell-free fetal DNA ("cffDNA") circulated in a pregnant woman's blood plasma and serum, the portion of maternal blood samples that was, until then, discarded as medical waste. They then amplified the cffDNA and searched for paternally inherited sequences, which allowed them to devise methods to diagnose fetal genetic conditions via noninvasive testing that was simpler and safer to use than the typical methods involving amniocentesis,² a discovery that revolutionized prenatal genetic testing.

In two recent opinions by the U.S. Court of Appeals for the Federal Circuit, each of these discoveries has been invalidated under 35 U.S.C. § 101 for being directed to patent-ineligible subject matter.³ These decisions have further added to the uncertainty of the Supreme Court's two-step patentable subject matter test elucidated in Mayo Collaborative Services v. Prometheus Laboratories, Inc.⁴ and Alice Corp. v. CLS Bank International,⁵ which had already led to lower court decisions invalidating life sciences method patents.

The Mayo/Alice Framework

35 U.S.C. § 101 states that "[w]hoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent."⁶ However, the Supreme Court has long held that there are exceptions to patent-eligible subject matter including laws of nature, natural phenomenon, and abstract ideas, as they are basic tools of science and technology.⁷ At the same time, though, the Supreme Court has recognized "that too broad an interpretation of this exclusionary principle could eviscerate patent law," and that an application of a law of nature may be deserving of patent protection.⁸

In Mayo and Alice, the Supreme Court set forth a two-step analysis for distinguishing patents that claim patent-ineligible subject matter from those that claim eligible applications of those concepts. In the first step of the analysis, the court determines whether the claim at issue is directed to a law of nature, natural phenomenon, or abstract idea.⁹ If it is, the second step searches for an "inventive concept"—whether the additional elements of the claim, both individually and as an ordered combination, transform the claim to a patent-eligible application.10 Implicit in this analysis is the idea that "patents that claim processes that too broadly preempt the use of a natural law" should be invalidated.¹¹

Ariosa and Genetic Technologies

In Ariosa Diagnostics, Inc. v. Sequenom, Inc.,¹² the Federal Circuit ruled that claims of U.S. Patent No. 6,258,540 were directed to ineligible subject matter. Claim 1 of the '540 patent claimed a method of "amplifying" the paternally-inherited DNA from the blood serum or plasma of a pregnant mother and "detecting" the presence of fetal DNA in the sample.¹³ The Federal Circuit first found that claim 1 "begins and ends with a natural phenomenon."¹⁴ Under step two of the analysis, the Federal Circuit found that each additional method step merely recited routine, conventional activities in 1997 and therefore was not new and useful enough to transform the invention to patent-eligible subject matter.¹⁵ Turning then to the issue of preemption—i.e., whether the claim was so broad as to preclude any practiced application of the discovery—the Federal Circuit cautioned that while "preemption may signal patent ineligible subject matter, the absence of complete preemption does not demonstrate patent eligibility."¹⁶

These last two aspects of the decision—the step two analysis and the preemption analysis—are critical, as the Federal Circuit likely broadened the already broad § 101 framework from the Supreme Court. If courts do not have to view the additional method steps of a claim as a whole, unexpected discoveries like in Ariosa, which take routine, conventional steps and apply them in a way that is unexpected and surprising, will not be found patent eligible. Further, the Federal Circuit's discarding of preemption as "moot" where the evidence indicated that there were examples of alternative uses of cffDNA outside the scope of the claims is concerning, as this was previously thought to be the cornerstone of this exception to patentable subject matter under Supreme Court jurisprudence.¹⁷

The Ariosa decision was reinforced by Genetic Technologies, Ltd. v. Merial L.L.C.¹⁸ Claim 1 of U.S. Patent No. 5,612,179 recited a method of detecting a coding region of a person's genome by amplifying and analyzing a linked non-coding region of that same person's genome. Before Genetic Technologies, there was a split in the lower courts regarding the patentability of claim 1. The first decision, in the U.S. District Court for the Northern District of California, Genetic Technologies, Ltd. v. Agilent Technologies, Inc.,¹⁹ found claim 1 of the '179 patent to be patent eligible, as the "amplifying" step transformed the claim, when "considered as a whole," to a patent-eligible concept and additional uses existed that were not preempted by the claim.²⁰ Seven months later, the U.S. District Court for the District of Delaware invalidated the same claim as patent-ineligible subject matter in Genetic Technologies, Ltd. v. Bristol-Myers Squibb Co.²¹

In Genetic Technologies, the Federal Circuit found that this claim was directed to a law of nature, due to the "similarity of claim 1 to the claims evaluated in Mayo and Ariosa."²² Under step two of the Mayo/Alice framework, the Federal Circuit held that "a claim directed to a newly discovered law of nature . . . cannot rely on the novelty of that discovery for the inventive concept necessary for patent eligibility; instead, the application must provide something inventive, beyond mere 'well-understood, routine, conventional activity.'"²³ Like Ariosa, the amplification and other method steps in claim 1 did not provide sufficient inventive concept to transform the claim into a patent-eligible concept.²⁴

Recent District Court Decisions Invalidating Method Claims

In Exergen Corp. v. Brooklands, Inc.²⁵ the method claim at issue was directed to the assertedly unexpected finding that body temperature could be determined from surface skin temperature measured at the forehead. The steps of the claim involved a "measuring" step (measuring the temperature at the forehead), and a "processing" step (taking the data from the measuring step and applying a mathematical formula to approximate core body temperature). These steps were found to be routine and conventional, since they only consisted of measuring the forehead temperature and applying a mathematical formula to the data, even though the prevailing thought at the time of the invention was that measuring internal body temperature from the forehead was impossible.²⁶

Similarly, in Celsis in Vitro, Inc. v. CellzDirect, Inc.,²⁷ the discovery at issue concerned the finding that certain liver cells were capable of being frozen and thawed more than once. The prevailing thought at the time of invention was said to be that liver cells could only be frozen once and then must be used or discarded.²⁸ In contrast with this thought, Celsis' U.S. Patent No. 7,604,929 claimed a method of "thawing" the previously frozen cells, "separating" the nonviable cells from the viable ones, and "refreezing" the cells. However, once again, the steps of thawing and refreezing the liver cells were found by the court to be routine and conventional when analyzed individually, because the same process used to freeze the cells twice was used to freeze the cells once.²⁹ Thus, the court held that the patent's method claims were directed to ineligible subject matter.³⁰

In another case involving the company Genetic Technologies, Genetic Technologies Limited v. Laboratory Corporation of America Holdings,³¹ the court invalidated U.S. Patent No. 7,615,342, which covered the unexpected discovery that certain genes in the human body are associated with physiological traits relating to athletic performance, which could allow the selection of those individuals more likely to become elite athletes.

Claim 1 of the patent claimed a method of "analyzing" a human sample, "detecting" the presence of the 577R allele, and "predicting" potential elite performance.³² The court determined that the method steps were no more than routine, conventional applications of a natural law, and dismissed the claim as patent ineligible.³³

There are yet other examples of life sciences discoveries that have been invalidated under the Mayo/Alice framework of 35 U.S.C. § 101. Lower courts have also invalidated a method for detecting a patient's risk for heart disease,³⁴ a method for determining whether particular types of pharmaceuticals are likely to be effective in treating lung cancer in a patient,³⁵ a method for determining whether a dog has (or might develop) canine exercise-induced collapse,³⁶ and a method for determining a nutritional diet for an animal based on the relationship between physiological conditions and genomic data.³⁷ In all of these cases, the lower courts reached their decision based on looking at the method steps individually (and not as a whole) or without addressing the preemption factor.

Could Method-of-Treatment Claims Be Next?

In Endo Pharmaceuticals Inc. v. Actavis Inc.,³⁸ the court held that plaintiffs' characterization of the claim at issue as a new and useful method for treating pain with an existing pharmaceutical compound instead of a law of nature was "thoroughly unconvincing." The patent at issue, U.S. Patent No. 8,871,779, covers a method of using oxymorphone (a known drug) in the treatment of pain by providing the patient with a dosage form and noting that the bioavailability of the drug is increased in renally-impaired patients.³⁹ While in this case, the drug was known and the method of using the drug to treat pain was also known, it was not known at the time of invention the relationship between the dosage of oxymorphone and renal impairment. While the court noted that it was not invalidating a method of treatment patent in this instance,⁴⁰ a footnote to the opinion arguably opened the door to potentially invalidating these types of methods in the future:

Plaintiffs' emphasis on the fact that this relationship between renal function and the effectiveness of oxymorphone was a new discovery, however, only adds support to the Court's understanding that Plaintiffs merely discovered a natural law (the way the human body reacts to a specific drug) and sought to patent the application of that natural law.⁴¹

It has been a cornerstone of patent law for many years that a discovery of a new, unexpected use of a known pharmaceutical compound provides an additional patentable discovery.⁴² However, under this new broad framework for patent eligibility under § 101, it could be argued that a new use of a known compound is merely a discovery of a previously unknown natural law (that the known compound can also be used to treat another illness). This would seem to be another example of a patent-ineligible concept under the Mayo/Alice Supreme Court framework.⁴³

Ameritox: A Sense of Hope?

In Ameritox, Ltd. v. Millennium Health, LLC,⁴⁴ a district court found the claimed method eligible for patent protection when viewing the method steps as a whole and finding no evidence that the claims had a preemptive effect. The discovery at issue in that case, similar to many of the cases above, covered the discovery that a urine screening method could determine whether a patient was adhering to a prescribed treatment plan—an idea said to be impossible at the time of invention.⁴⁵ However, in this case, the court ruled that the combination of steps produced a new and useful result when "examined as an ordered combination," noting that "if inventors engage in activities that run counter to scientific thought, those activities can hardly be considered conventional under § 101."⁴⁶ While this case was decided prior to the Federal Circuit's decision in Ariosa, the district court's reasoning shows how a life science method claim under the Mayo/Alice framework can be upheld using the proper two-step analysis from the Supreme Court.⁴⁷

What is clear from these recent decisions is that many lower courts are applying the Supreme Court's Mayo/Alice framework to determine the patent eligibility of life sciences claims in ways that are invalidating many inventions that previously may well have passed muster. Sequenom recently filed a petition for writ of certiorari for the Supreme Court to hear its appeal from the Federal Circuit's Ariosa decision.⁴⁸ Many amici have also filed briefs in support of the Court hearing the case. If the Supreme Court agrees to hear the case, it could shed some further light on this evolving area of law.⁴⁹

1. Genetic Techs. Ltd v. Merial L.L.C., Nos. 2015-1202, 2015-1203, 2016 BL 110883, at *1-2 (Fed. Cir. April 8, 2016).
2. Petition for Writ of Certiorari, Sequenom, Inc. v. Ariosa Diagnostics, Inc., U.S., No. 15-1182 (March 21, 2016).
3. Genetic Techs., 2016 BL 110883, at *10; see Ariosa Diag-nostics, Inc. v. Sequenom, Inc., 788 F.3d 1371, 1380 (Fed. Cir. 2015); see also, Ariosa Diagnostics, Inc. v. Sequenom, Inc., 809 F.3d 1282, 1284 (Fed. Cir. 2015) (denying en banc review); see also, Assoc. for Molecular Pathology v. Myriad Genetics, Inc., 133 S.Ct. 2107 (2013) (finding that the discovery of the precise location and sequence of the BRCA1 and BRCA2 genes, which if mutated can dramatically increase the risk of breast and ovarian cancer, was a patent-ineligible invention as it was merely a discovery of a natural law); see also, In re BRCA1- & BRCA2-Based Hereditary Cancer Test Patent Litigation, 774 F.3d 755 (Fed. Cir. 2014) (finding method claims utilizing the BRCA1 and BRCA2 discovery patent ineligible under § 101).
4. 132 S.Ct. 1289. 1296-97 (2012).
5. 134 S.Ct. 2347, 2355 (2014).
6. 35 U.S.C. § 101 (2006).
7. Mayo, 132 S.Ct. at 1293.
8. Id. at 1293-94.
9. Id. at 1297; see also, Alice, 134 S.Ct. at 2355.
10. Mayo, 132 S.Ct. at 1298; see also, Alice, 134 S.Ct. at 2355.
11. Mayo, 132 S.Ct. at 1294.
12. 788 F.3d 1371 (Fed. Cir. 2015).
13. Id. at 1373-74.
14. Id. at 1376.
15. Id. at 1377.
16. Id. at 1379.
17. Judge Linn's concurrence highlights some of these issues, as he expressed concern that the sweeping language in Mayo led to the "perhaps unintended" consequence of "excluding a meritorious invention from the patent protection it deserves." Id. at 1380. Four additional Federal Circuit judges expressed concern over the decision in the court's denial of re-hearing en banc. See Ariosa, 809 F.3d at 1282.
18. 2016 BL 110883, at *1-2.
19. 24 F. Supp. 3d 922 (N.D. Cal. 2014).
20. Id. at 930-32.
21. 72 F. Supp. 3d 521 (D. Del. 2014). This decision was appealed to the Federal Circuit by Genetic Technologies. The Northern District of California case was dismissed by joint stipulation on the same day the Delaware decision came out, Oct. 30, 2014. See Genetic Techs., Ltd. v. Agilent Techs., Inc., Case No. 3:12-cv-01616-RS, D.I. 124 (N.D. Cal. Oct. 30, 2014).
22. Genetic Technologies, 2016 BL 110883, at *6.
23. Id. (citing Mayo, 132 S.Ct. at 1294).
24. Id. at *7.
25. No. 12-12243-DPW, 2015 BL 279905, at *4 (D. Mass. Aug. 28, 2015).
26. Id. at *6; see also, Exergen Corp. v. Thermomedics, Inc., No. 13-11243-DJC, 2015 BL 311319, at *6 (D. Mass. Sept. 15, 2015) ("No matter how novel the concept of measuring body temperature from forehead skin temperature or how valuable the contribution to the medical community, this idea as set forth in the asserted claims is fundamentally a discovery of a natural relationship between skin temperature and body temperature.") (finding same). But see, Exergen Corp. v. Kaz USA, Inc., No. 13-10628-RGS, 2015 BL 400894 (D. Mass. Dec. 7, 2015) (analyzing different claims in different related patents finding certain claims pass the motion to dismiss stage for patentable subject matter).
27. Celsis in Vitro, Inc. v. CellzDirect, Inc., 83 F. Supp. 3d 774 (N.D. Ill. 2015).
28. Id. at 777-78.
29. Id. at 778-79.
30. Id. at 783. The court also found that while the claims were more narrowly drawn than the claims at issue in Mayo and Alice and do not preempt the natural law in its entirety, this did not weigh against the finding of patent ineligibility. Id. at 785.
31. No. 12-1736-LPS-CJB, 2014 BL 243747 (D. Del. Sept. 3, 2014).
32. Id. at *2.
33. Id. at *10-12.
34. See Cleveland Clinic Found. v. True Health Diagnostics LLC, No. 1:15 CV 2331, 2016 BL 51904, at *1, *7 (N.D. Ohio, Feb. 23, 2016) ("Plaintiff argues that the patent satisfies § 101 because it does not preempt the entire field since it does not foreclose the use of other current or future MPO measuring techniques. The argument is rejected.") (citing Ariosa, 788 F.3d at 1379); see also Cleveland Clinic Found. v. True Health Diagnostics LLC, No. 1:15 CV 2331, 2015 BL 382088 (N.D. Ohio, Nov. 18, 2015) (denying request for preliminary injunction based on same reasoning).
35. See Esoterix Genetic Labs. v. Qiagen Inc., 133 F. Supp. 3d 349, 358 (D. Mass. 2015) ("Thus, none of the additional steps, considered individually, added any innovation worthy of patent protection to the basic law of nature that was recited in the claims.") (emphasis added).
36. See Genetic Veterinary Scis., Inc. v. Canine EIC Genetics, LLC, 101 F. Supp. 3d 833, 844 (D. Minn. 2015) ("Outside of the natural law relationship between the T767 allele and EIC, the techniques or methods identified in the claims, whether viewed individually or in the aggregate, were at the time the patent was issued 'well-understood, routine, and conventional techniques that a scientist would have thought of when instructed to' test whether a certain allele exists at a specific genetic location.") (quoting BRCA, 774 F.3d at 764). Judge Tunheim's decision did not even mention the preemption factor involved in the 101 analysis.
37. See Hemopet v. Hill's Pet Nutrition, Inc., No. CV 12-01908-JLS, 2014 BL 454981, at *6-7 (C.D. Cal. Nov. 24, 2014) ("The Court agrees with Hemopet that this final step in the claims, creating a nutritional product for dogs and cats, is an additional step not found in previous claims the Supreme Court has addressed. However, the Court finds Hill's to be correct that this step is nothing more than a general 'apply it' step that does not transform an otherwise ineligible-patent concept into a patentable invention.") (internal citations omitted).
38. No. 14-1381-RGA, 2015 BL 378267 (D. Del. Nov. 17, 2015).
39. Endo Pharms. Inc. v. Actavis Inc., No. 14-1381-RGA, 2015 BL 307717, at *1 (D. Del. Sept. 23, 2015) (report and recommendation from magistrate judge).
40. Endo Pharms., 2015 BL 378267, at *4 ("Plaintiffs here claimed a widely-used, well-known method of treating pain. The only new aspect of the '737 patent was to tell doctors to adjust the dosage of oxymorphone based upon their discovery of a natural law—namely, how the bodies of individuals with renal deficiencies process the drug. No creative steps or inventive leaps aside from the discovery of a natural law are contemplated here. The patent merely tells doctors to apply a natural law. Accordingly, this case is hardly the poster child for a policy argument on the wide-ranging implications of a § 101 rejection of a pharmaceutical method patent.").
41. Id. at *4 n.4.
42. See In re Hack, 245 F.2d 246, 248 (C.C.P.A. 1957).
43. See also, Bristol-Myers Squibb Co. v. Merck & Co., No. 15-560-GMS, 2016 BL 81845, at *1 n.1 (D. Del. March 17, 2016) (finding that a method-of-treatment claim for an anti-cancer biologic compound was directed to a natural law, but denying Merck's motion to dismiss under § 101 because whether "the claims amount to an implementation step is a complicated factual determination that the court could better resolve after discovery.").
44. Ameritox, Ltd. v. Millennium Health, LLC, 88 F. Supp. 3d 885 (W.D. Wis. 2015).
45. Id. at 889-90.
46. Id. at 907, 912 (emphasis in original).
47. See also, Rutgers v. Qiagen N.V., No. 15-cv-7187 (PGS)(LHG), 2016 BL 59500, at *5 (D.N.J. Feb. 29, 2016) (denying motion to dismiss under § 101 because the "Rutgers inventions satisfy [the 101] test by greatly improving upon the prior practice" and the method claims are "limited to the specific application of diagnosis of human TB infections" and are therefore not preemptive).
48. Petition for Writ of Certiorari, Sequenom, Inc. v. Ariosa Diagnostics, Inc., No. 15-1182 (March 21, 2016).
49. Not only the courts are struggling with this—so is the U.S. Patent and Trademark Office, which in a recent May 2016 revision to its 2014 and 2015 Guidance on Patent Subject Matter Eligibility provides updated guidance to patent examiners regarding the patent eligibility of subject matter related to natural products. May 2016 Subject Matter Eligibility Update, 81 Fed. Reg. 27,381 (May 6, 2016).