Vanda v. Roxane Labs. – Are Two Natural Laws Better Than One?

iStock_000007770475_SmallAs you will recall, in Prometheus v. Mayo, the Supreme Court held that a claim reciting a natural law had to have other non-conventional steps to pass muster under s. 101. The natural law in Mayo was the correlation between the concentration of the metabolite of the immunosuppressive drug and the efficacy of the drug – unpleasant side effects at the high end of the recited range and lack of efficacy at the low end. The Mayo Court wrote: “We need not, and do not, decide whether were the steps at issue here less conventional, these features of the claims [the administering, determining and recognition steps] would prove sufficient to invalidate them.” It was unnerving that the invalidated claims were method-of-treatment claims.

In his opinion in a Hatch-Waxman litigation involving the anti-schizophrenia drug Iloperidone, Vanda Pharms., Inc. v. Roxane Labs., Inc., Civil Action No. 13-1973-GMS; 14-757-GMS (D.Del., 2016), Judge Sleet upheld the validity  of the compound and the method claims in Reissue Patent No. 39,198 and US Patent No. 8,586,610.

The court began by finding the compound claims unobvious. The method claims had been attacked as failing s. 101. I assume that the original method of treatment claims are in the ‘198 patent, which is about to expire. Iloperidone had been the subject of clinical trials by Novartis, but development had been abandoned because the drug unpredictably caused a serious heart irregularity called QTc.

Vanda developed a companion diagnostic test and filed “regimen type claims” that were written as method of treatment claims. (I don’t know why, if a claim to a drug is unobvious, any method of using it is not unobvious as well. In re Pleuddemann, 910 F.2d 823 (Fed. Cir. 1990). In fact, Judge Sleet found that the method claims were unobvious following a full-scale s. 103 analysis. At the worst, he effectively ruled that the claims were directed to a new use of an “existing drug”, a claim form endorsed as patent eligible in Mayo dictum.)

But I digress. The method claim in question (I will discuss claim 6) was drawn to a method for treating a patient with Ilopridone comprising (a) genotyping a biological sample from a schizophrenic patient to determine if the patient has a CYP2D6 “poor metabolizer” genotype. Such patients are administered doses of the drug that are less than 12 mg per day that was found to lower their risk of QTc. Patient found not to have the poor metabolizer genotype are administered 12-24 mg/day  of the drug.

Roxane argued that the method patent “embodies two laws of nature: (1) that mutations in the CYP2D6 genes can alter its enzymatic activity (2) that a patient’s CYP2D6 enzymatic activity affects their metabolism of Iloperidone” and that Vanda just added a conventional dose adjustment to reduce the risk of a side effect. But, in this case, in addition to pointing out that claim 6 is not an attempt to patent “the relationship between Iloperidone, CYP2D6 metabolism and Qtc”, Vanda brought  many of its successful non-obviousness arguments to bear on this question.

Vanda argued that the ‘610 method patent was not the result of routine and conventional testing, e.g., that clinical study design is not routine or conventional. Vanda argued that adjusting the doses of similar drugs that are poor metabolizers did not eliminate the QTc side effect and that the original examiner allowed the claims as not barred by the Mayo test after the dosing limitations were added to the claims.

Judge Sleet agreed with Roxane that the claims depend on the relationship between the drug, CYP2D6 metabolism and the QTc side effect, and then, in part 2 of the Mayo test, looked for an additional step that would “transform the claims, making them valid.” Here the Judge was convinced that there was a combination of elements “sufficient to ensure that the claims amount to significantly more than just a natural law.”

The Judge was swayed by the argument that the dosage step does not apply to all patients as in Mayo, but only the population that exhibited the specific mutation:

“The dosage step requires applying genetic tests in a high specified way. Moreover, the process of using the genetic test to inform the dosage adjustment recited in the claims was not routine or conventional and amounted to more than an mere instruction to apply a natural relationship.” Importantly, the Judge gave weight to the recognition of the meaning of the correlations in the claim as involving “the human ingenuity that comes from applying a natural discovery in a way that achieves a ‘new and useful end’”[citing Cellzdirect, Diehr and Alice].

Finally, he distinguished Mayo-type preemption from the present case that would not preempt biological sampling or genotyping.

I can only hope that this decision helps establish that the use of one test to divide a population of patients into two or more groups (of responders vs. non-responders), and then treating the groups differently will pass step 2 of the Mayo test. The ‘610 patent does not expire until 2027, so this decision may well be appealed to the Fed. Cir.

View Vanda V. Roxane Labs

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2 Responses to Vanda v. Roxane Labs. – Are Two Natural Laws Better Than One?

  1. Paul Cole says:

    I seem to remember some years ago re-writing the Mayo claims as method of treatment (US) and product for use (EPO) and arguing that such claims would have avoided eligibility issues. The Roxane decision supports that contention.

    On the first Mayo step Vanda argued that it merely “involves a patent ineligible concept” which is insufficient to satisfy the “directed to” requirement. Although this argument was not successful, it seems to me to be serious and worth running in future cases. If my recollection is right it succeeded in the Federal Circuit in Enfish. Although the method of administration “depends on” natural laws, in my submission that is insufficient to establish that it is “directed to” those natural laws. As I put it in the European Representative’s brief to the Supreme Court in the Ariosa case, a method of cooking an omelette involves eggs and in the words of the court here “depends on” eggs, but that does not mean that it is “directed to” eggs. The argument that the first Mayo step is satisfied is, in my submission, weak.

    The Judge’s conclusion on the second step is almost a textbook analysis of ordered combination and is worth quoting, at least in part:

    “As the Federal Circuit instructed in Rapid Litig. Mgmt. Ltd v. CellzDirect, Inc., No. 2015-1570, 2016 WL 3606624 (Fed. Cir. July 5; 2016), a “particular
    ‘combination of steps”‘ can lead to valid patent claims that depend upon a natural relationship. Id at *4 (quoting Diehr, 450 U.S. at 188). This is true even though the individual steps may have been well known. Id at *7 “To require something more … would be to discount the human ingenuity that comes from applying a natural discovery in a way that achieves a ‘new and useful end.”‘ Id (quoting Alice, 134 S. Ct. at 2354). Finally, the court is persuaded that the concern articulated in Mayo that “patent law not inhibit further discovery by improperly tying up the future use of laws of nature” does not apply here, because the ‘610 Patent will not preempt biological sampling or genotyping. Mayo Collaborative Servs., 132 S. Ct. at 1301; (D.I. 178 at 24).”

    If you look at Mayo, all the claimed human activities were pre-invention (both the administration and analysis for the metabolite) and the only novel feature was bare information about the dosage. The novel feature, considered individually, did not fit into any of the four section 101 eligibility categories. Here there were post-invention human activities in administering the drug in an ordered regime, and these activities clearly fall into the “process” category of Section 101. It would have been very surprising if the court had reached a different conclusion on eligibility.

    In my submission the Judge’s analysis on section 101 was spot on, and would be difficult to reverse on appeal.

  2. What is particularly scary about Mayo is, as you say, that the claims could have easily been written as method-of-treatment claims;

    “A method to treat patient having an autoimmune disorder comprising:
    administering a 6-TP producing drug (e.g; AZA) to the patient so that 6-TP falls within the range of x mcg/ml and y mcg/ml.”

    Such claims may well be anticipated or be obvious by studies on AZA metabolism in the past, but would this claim fail the Mayo test? The S. Ct. saw the regimen claim put before them as an attempt to patent an old use for an old compound (since the numerical value range limits were in the determining step, they were given no weight.) The natural phenomenon that the S Ct identified was between the concentration of the drug and the likelihood of unacceptable side effects or lack of efficacy.

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