Mayo at Five: Are Traditional Method of Treatment Claims in Danger Under Section 101?

Just over five years ago, the Supreme Court began reshaping the concept of patent-eligible subject matter in the life sciences with its decision in Mayo v Prometheus.[i] The Mayo case introduced a new two-step test for patent eligibility, under which courts must first determine whether claims are directed to a patent-ineligible concept and, if the answer is "yes," must then search for an "inventive concept" by determining whether additional elements "transform the nature of the claim" into a patent-eligible application.[ii]

In our first of a series of blog posts on the evolving jurisprudence on Section 101 in the life sciences, we examined how courts have treated diagnostic claims under the Mayo test, and concluded that they have not fared well, with nearly every decision post-Mayo finding diagnostic claims patent ineligible under Section 101.

Have method of treatment claims fared better? After Mayo, the Supreme Court noted that scientists who discover natural laws or phenomena are "in an excellent position to claim applications of that knowledge."[iii] More directly, the Federal Circuit has dismissed the idea of finding "patent ineligible methods of, say … treating cancer with chemotherapy (as directed to cancer cells' inability to survive chemotherapy), or treating headaches with aspirin (as directed to the human body's natural response to aspirin).[iv] These and similar pronouncements led some in the life sciences community to believe that method of treatment claims were less likely to fall under Section 101 than their diagnostic counterparts.[v]

Despite the optimism, the results thus far have been mixed. Several district court decisions have rejected eligibility challenges to method of treatment claims. But, even when finding claims patent eligible, a number of district court decisions have found claims including treatment steps to satisfy the first prong of the Mayo test. (See Bristol-Myers Squibb[vi], Vanda[vii].) And, in other cases, courts have actually found method of treatment claims patent ineligible under Mayo. (Endo[viii], Boehringer Ingelheim[ix].) The Federal Circuit has not yet issued an eligibility decision on method of treatment claims post-Mayo, but the district court decisions have caused some in the pharmaceutical industry to fear that nearly all pharmaceutical method of treatment claims could be at risk because, at some level, all treatments are based on natural phenomenon.[x]

In this blog post, we briefly recap the important district court decisions and USPTO guidance on Section 101 for method of treatment claims post-Mayo. Our linked full-length article provides an in-depth analysis of how courts have treated method of treatment and various other types of life sciences patent claims in the wake of Mayo.

Two District Court Decisions Have Refused to Find Method of Treatment Claims Patent Ineligible But Did Find They Satisfied Step One of the Mayo Test

In at least two decisions, although not finding claims ineligible, district courts have found method of treatment claims satisfied step one of the Mayo/Alice test.

In March 2016, in Bristol-Myers Squibb Co. v. Merck & Co., Judge Sleet of the District of Delaware denied a motion to dismiss based on § 101 but found that a method of treatment claim, without any diagnostic limitation, satisfied step one of the Mayo/Alice test.[xi] The claims at issue were directed to treating cancer by administering a solution including an anti-PD-1 human antibody.[xii] The antibody solution blocked a pathway in the body that suppressed immune response, called the PD-1 pathway and allowed T-cells to attack and remove cancer cells from the body.[xiii]

The court found Mayo/Alice step one was satisfied because the claims "touch[ed] upon" a natural phenomenon "by using T cells to activate the immune system":

First, the court concludes that, contrary to Bristol-Myers contention, the ‘994 patent touches upon a natural phenomenon by using T cells to activate the immune system. The ‘994 patent relies on the known scientific fact that blocking activation of the PD-1 pathway causes this effect in the body, which enables the patient’s T cells to perform their normal biological activity of removing cancer cells. This interaction is a natural phenomenon.[xiv]

As for step two, the court held it was "a complicated factual determination that the court could better resolve after discovery."[xv]

Later the same year, in Vanda Pharmaceuticals Inc. v. Roxane Labs., Inc,[xvi] Judge Sleet found that claims relating to Vanda Pharmaceutical's Fanapt® product used for the treatment of schizophrenia satisfied step one of the Mayo/Alice test but were saved by step two. The claims at issue included a first determination step to identify whether the patient is a CYP2D6 poor metabolizer via a genotyping assay and, second, an administration step where iloperidone is administered to a patient in a certain amount depending on whether the patient was determined to be a CYP2D6 poor metabolizer.[xvii]

Applying the Mayo/Alice two-part test, the court found the first step satisfied because the asserted claims "depend" upon a law of nature, "the relationship between iloperidone, CYP2D6 metabolism, and QTc prolongation."[xviii] However, with respect to step two, the court did not find the claims patent ineligible, reasoning that the patent "does not apply to all patients, but only a specific patient population based upon their genetic composition," and that "the process of using this genetic test to inform the dosage adjustment recited in the claims was not routine or conventional and amounted to more than a mere instruction to apply a natural relationship."[xix]

Other District Court Decisions Have Found Method of Treatment Claims Patent Ineligible

Several other district court decisions have not only found method of treatment claims satisfy step one of the Mayo/Alice test, but went on to find that they are patent ineligible.

In 2015, in Endo Pharmaceuticals Inc. v. Actavis Inc., Judge Andrews from the District of Delaware held ineligible under § 101 claims to a method of treating pain with oxymorphone in renally impaired patients.[xx] The claims, as characterized by the court, told "doctors to take an existing pharmaceutical compound for treating pain and 1) measure the creatinine clearance rate of the patient using an existing method, 2) use an unpatentable law of nature to assess the bioavailability of oxymorphone in light of the patient’s creatinine clearance rate, 3) reconsider drug dosage in light of the law, and 4) administer that dosage."[xxi] On step one of the Mayo/Alice test, the court found that "the subject matter of the invention is the connection between the severity of renal impairment and the bioavailability of oxymorphone, or, in other words, the reaction of the human body of a renally impaired individual to oxymorphone, which is unquestionably a natural law."[xxii] Regarding step two, Judge Andrews found that, even though the claim required the doctor to orally administer a lower dose based on the level of renal impairment, the patent did no more than tell doctors to apply the natural law.[xxiii]

Later in 2016, the District of New Jersey, at the motion to dismiss stage, found ineligible under § 101 claims reciting a method for treating metabolic diseases in Boehringer Ingelheim Pharmaceuticals, Inc. v. HEC Pharm Co.[xxiv] The patent generally related to treatments of metabolic diseases using DPP-IV inhibitors.[xxv] The use of certain DPP-IV inhibitors to treat metabolic diseases was known, but the patent disclosed DPP-IV inhibitors that purported to improve upon conventional DPP-IV inhibitors.[xxvi] Of particular note, the patent included claims to treating type 2 diabetes with a specific Boehringer Ingelheim DPP-IV inhibitor identified by chemical structure in the claim.[xxvii]

Under Step 1 the court found the patent was directed to an abstract idea because the "improvement over the conventional DPP-IV inhibitors is that the DPP-IV inhibitors disclosed in the '156 patent are mainly excreted via the liver, and only to a minor extent via the kidney, in order to treat the targeted patient population."[xxviii] According to the court, the claims reciting the specific compound "simply recite a single instruction of administering a drug to a targeted patient population, which is an abstract idea."[xxix] On step 2, the court found the claims did not add enough to transform the abstract idea into patent-eligible subject matter because the problems with using conventional DDP-IV inhibitors to treat metabolic diseases were "known and well-understood in the scientific community," and the additional features recited by the claims were only limiting the use or dose of the DDP-IV inhibitors to specific diseases or describing known methods for structurally modifying the DPP-IV inhibitors.[xxx]

Most recently, in Natural Alternatives International, Inc. v. Allmax Nutrition, Inc., the Southern District of California granted the defendant's motion to dismiss, finding that the four asserted patents claimed ineligible subject matter under § 101.[xxxi] One of the four patents claimed methods of increasing the amount of beta-alanylhistidine in human tissue by "providing an amount of beta-alanine to blood or blood plasma" and "exposing the tissue to the blood or blood plasma, whereby the concentration of beta-alanylhistidine is increased in the human tissue."[xxxii]

The court found the first step of the Mayo/Alice test satisfied because "the principle that ingesting beta-alanine, a natural substance, will increase carnosine concertation in tissue and, thereby, aid in regulating the hydronium ion concentration in the tissue" was a law of nature.[xxxiii] Regarding step two, the court reasoned that the claims did not require beta-alanine from non-natural sources and, thus, the claims encompassed "natural methods of exposing beta-alanine to human tissue."[xxxiv] Even if the plaintiff was correct that the patent disclosed a new and useful method of using a natural product for increasing the amount of carnosine in muscles, the court found that was "insufficient to render the claims at issue patent eligible."[xxxv]

USPTO Guidance Suggests That Adding Administering Steps May Make Claims Patent-Eligible

In contrast to some district court decisions, the USPTO's Subject Matter Eligibility Examples[xxxvi] suggest that adding an administering step may make claims patent eligible. Continuing on with the "julitis" examples discussed in our prior blog post regarding the patentability of diagnostic claims, the guidance includes two additional claims which, in addition to requiring detection of the JUL-1 antibody in the patient to diagnose them with julitis, each add a step of administering vitamin D or anti-tumor necrosis factor (TNF) antibodies to treat the patient.[xxxvii]

According to the USPTO, if one assumes that the administration of vitamin D to treat julitis was not "widely prevalent in the field" the claim element administering vitamin D makes the claimed subject-matter eligible because it comprises "an unconventional step that is more than a mere instruction to '€˜apply' the [natural] correlation."[xxxviii] Alternatively, the use of anti-TNF antibodies to treat julitis was well-understood and conventional in the USPTO's example, but doctors frequently misdiagnosed julitis as rosacea using conventional diagnostic techniques.[xxxix] In that case, the USPTO views the combination of steps as "transformative" and patent-eligible because it "ensure[d] that patients who have julitis will be accurately diagnosed (due to the detection of JUL-1 in their plasma) and properly treated with anti-TNF antibodies, as opposed to being misdiagnosed as having rosacea as was previously commonplace."[xl]

Conclusion

Despite statements from the Supreme Court and Federal Circuit suggesting method of treatment claims are more likely patent eligible, district court decisions have put the eligibility of such claims in jeopardy.

Decisions such as Bristol-Myers Squibb or Vanda demonstrate how easily courts can find that claims satisfy step one of the Mayo test. Some would argue that, under Judge Sleet's analysis in those cases, every method of treatment claim would pass step one because, at some level, all treatments are based on natural phenomenon. Others may argue that Judge Sleet did not correctly apply Mayo because he found the claims "touched upon" or "depend on" a law of nature, not that they were "directed to" a law of nature.

Decisions such as Endo and Natural Alternatives show that at least some district courts are finding the addition of a treatment step alone is not enough to categorically save claims from being found patent ineligible under Section 101. Indeed, the Boehringer Ingelheim decision, although heavily criticized by some,[xli] shows that some district courts have even found methods of treatment using a specific chemical compound patent ineligible under Mayo.

The jurisprudence will certainly continue to develop in this area, as the Federal Circuit is likely to weigh in on some of these and other method of treatment claim decisions in the future. But, at least for now, some method of treatment claims may be susceptible to Section 101 attacks at the district court level.

[i] Mayo Collaborative Servs. v. Prometheus Labs., Inc., 566 U.S. 66 (2012).

[ii] Id. at 77-78.

[iii] See Ass'n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2120 (2013).

[iv] Rapid Litig. Mgmt. v. CellzDirect, Inc., 827 F.3d 1042, 1049 (Fed. Cir. 2016).

[v] See, e.g., https://www.uspto.gov/sites/default/files/documents/comments_PHRMA_Jan182017.pdf at 6 ("This is a surprising decision since a claim directed to a method of administering a compound to a patient is not an abstract concept and is generally perceived as an appropriate claim form for claiming methods relating to pharmaceutically active compounds."); Warren Woessner, Rapid Litigation v. CellzDirect —€“ A Break in the Section 101 Wall, National Law Review (July 5, 2016), available at https://www.natlawreview.com/article/rapid-litigation-v-cellzdirect-break-section-101-wall ("[T]he aspirin example seems to leave method of treatment claims safe from s. 101.").

[vi] Bristol-Myers Squibb Co. v. Merck & Co., Civil Action No. 15-572-GMS, 2016 WL 1698385 (D. Del. Mar. 29, 2016).

[vii] Vanda Pharms. Inc. v. Roxane Labs., Inc., 203 F. Supp. 3d 412 (D. Del. 2016).

[viii] Endo Pharms. Inc. v. Actavis Inc., Civil Action No. 14-1381-RGA, 2015 WL 7253674 (D. Del. Nov. 17, 2015).

[ix] Boehringer Ingelheim Pharms., Inc. v. HEC Pharm Co., Civil Action No. 15-cv-5982 (PGS)(TJB), 2016 WL 7177704 (D.N.J. Dec. 8, 2016).

[x]See https://www.uspto.gov/sites/default/files/documents/comments_PHRMA_Jan182017.pdf at 5-6.

[xi] Bristol-Myers Squibb, 2016 WL 1698385.

[xii] Id. at *1 n.2.

[xiii] Id.

[xiv] Id.

[xv] Id. The parties stipulated to dismissal before trial began, on January 20, 2017.

[xvi] Vanda Pharms., 203 F. Supp. 3d.

[xvii] Id. at 419.

[xviii] Id. at 428-29.

[xix] Id. at 429. Vanda is currently on appeal to the Federal Circuit.

[xx] Endo Pharms., 2015 WL 7253674.

[xxi] Id. at *2.

[xxii] Id. at *3.

[xxiii] Id. at *3-4.

[xxiv] Boehringer Ingelheim, 2016 WL 7177704.

[xxv] Id. at *1.

[xxvi] Id. at *2.

[xxvii] U.S. Patent No. 8,853,156 at 32:48-65 (claims 24 and 25).

[xxviii] Id. at *9.

[xxix] Id. at *13.

[xxx] Id. at *10-13. Although the court found the claims of this patent invalid, the case continued on other asserted patents. Plaintiffs moved to sever the claims related to the ineligible patent so that a final judgment of invalidity could be entered and they could appeal. But, on April 17, 2017, the court denied plaintiffs' motion.

[xxxi] Natural Alternatives Int'l, Inc. v. Allmax Nutrition, Inc., Case No.: 16-cv-01764-H-AGS, 2017 WL 2733923 (S.D. Cal. June 26, 2017).

[xxxii] Id. at *11.

[xxxiii] Id.

[xxxiv] Id.

[xxxv] Id. at *12.

[xxxvi] https://www.uspto.gov/sites/default/files/documents/ieg-may-2016-ex.pdf.

[xxxvii] Id. at 10-11.

[xxxviii] Id. at 14.

[xxxix] Id. at 15.

[xl] Id.

[xli] https://www.uspto.gov/sites/default/files/documents/comments_PHRMA_Jan182017.pdf at 6 ("This is a concerning decision which, if upheld, could dampen innovation incentives."); Woessner, supra note v.

Authors: Geoffrey D. Biegler, Megan A. Chacon, Dalia Kothari.