Pain Treatment, Kidney Failure, and §101
Endo Pharmaceuticals Inc. v. Teva Pharmaceuticals USA, Inc., 2017-1240, 2017-1455, 2017-1887 (Fed. Cir. March 28, 2019)
In Endo Pharmaceuticals Inc. v. Teva the Federal Circuit has further clarified the patent eligibility of treatment methods which include natural elements. The Opinion, which includes comparisons with other cases such as Vanda, CellzDirect and Ariosa Diagnostics, leaves one crafting such claims on ground that is fairly firm.
The dispute in this case involved Endo’s patent U.S. 8,808,737 (‘737 Patent) which relates to methods for the treatment of pain in renal patients. It has long been recognized that controlled -release dosage forms of pain relief are important to maintain proper levels in the body. However, this is even more challenging with patients having kidney problems. The ‘737 Patent leverages work performed relating oxymorphone content in the bloodstream, measured as AUC, to creatinine clearance. Creatinine in the blood is removed by the kidneys, so that higher levels of creatinine correlate to poorer kidney function. A range of kidney performance (healthy, mild renal impairment, moderate renal impairment, and severe renal impairment) can be defined relating to a corresponding range (high to low) of creatinine clearance. The patent data demonstrates that as kidney function deteriorates, especially with moderate or severe renal impairment, oxymorphone AUC’s increase rapidly. The patent claims, therefore, set out a method for taking renal impairment into account when administering oxymorphone.
When Endo sued Actavis for infringement of claims 1-6 of the ‘737 Patent, Activis moved for dismissal based on the theory that the claims were ineligible subject matter under §101. A magistrate, analyzing the case under the Alice/Mayo test, found the claims ineligible, reasoning that the steps were similar to those of Mayo. With respect to the administering step, the magistrate indicated
The administering step simply limits the relevant audience to patients and prescribing physicians, who treat chronic or acute pain with oymorphone, and instructs the administration of the correct dosage of oxymorphone depending on the severity of the renal impairment, a step very similar to Mayo, which limited the relevant audience to “doctors who treat patients with certain diseases with thiopurine drugs.
The District Court agreed with the Magistrate, particularly with the comparison of the claims to that of Mayo. Endo appealed.
In rejecting the District Court’s analysis, the Federal Circuit approvingly cited the holding and claims in Vanda as an example of treatment claims meeting the requirements of §101. Table 1 summarizes claim 1 of both the ‘737 Patent and Vanda.
|Claim 1||‘737 Patent||Vanda|
|A method of treating pain in a renally impaired patient, comprising the steps of:||A method for treating a patient with iloperidone, wherein the patient is suffering from schizophrenia, the method comprising the steps of:|
|a. providing a solid oral controlled release dosage form, comprising: i. about 5 mg to about 80 mg of oxymorphone or a pharmaceutically acceptable salt thereof as the sole active ingredient; and ii. a controlled release matrix;|
|b. measuring a creatinine clearance rate of the patient and determining it to be (a) less than about 30 ml/min, (b) about 30 mL/min to about 50 mL/min, (c) about 51 mL/min to about 80 mL/min, or (d) above about 80 mL/min; and||determining whether the patient is a CYP2D6 poor metabolizer by: obtaining or having obtained a biological sample from the patient; and performing or having performed a genotyping assay on the biological sample to determine if the patient has a CYP2D6 poor metabolizer genotype; and|
|c. orally administering to said patient, in dependence on which creatinine clearance rate is found, a lower dosage of the dosage form to provide pain relief;
wherein after said administration to said patent, the average AUC of oxymorphone over a 12-hour period is less than about 21 ng-hr/mL.
|if the patient has a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount of 12 mg/day or less, and
if the patient does not have a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in
an amount that is greater than 12 mg/day, up to 24 mg/day,
wherein a risk of QTc prolongation for a patient having a CYP2D6 poor metabolizer genotype is lower following the internal administration of 12 mg/day or less than it would be if the iloperidone were administered in an amount of greater than 12 mg/day, up to 24 mg/day
The Federal Circuit Opinion, together with the claims of the ‘737 Patent and Vanda provide key lessons for avoiding §101 problems in crafting method of treatment claims.
- The claim as a whole is evaluated
The Federal Circuit repeated that the claims must be read as a whole. This reinforces the Bahr memo issued to Examiners previously, as mentioned above.
- Treatment methods are eligible, detection methods or observation are not.
The Federal Circuit differentiated treatment claims that are eligible from detection methods, that are not, as in the Ariosa & Athena Diagnostics decisions. The claims found ineligible in Ariosa were directed to a method for detecting paternally inherited cell-free fetal DNA. In Athena, the Federal Circuit observed that the claims related to a natural law and conventional means for detecting it. A key point when considering these treatment claims is to understand that the natural ability of an element in a claim to be incorporated in the method does not mean that the claim is directed to that natural ability. In CellzDirect the claims were directed to a method for freezing hepatocytes.
To be patent eligible, the treatment method claim should contain specific steps. In contrast to the Mayo claims where a thiopurine drug was simply administered to a patient, the Federal Circuit noted that the Endo claims are directed to an application of a drug treatment for a particular disease, where a specific dose was administered based on the results of kidney function testing. Likewise in Vanda, doctors administered iloperidone for schizophrenia, with dosages based on whether the patient had a CYP2D6 poor metabolizer genotype. The claims were not directed to a method for corelating the “natural phenomenon” of poor kidney function (in Endo) or to measuring genotype (in Vanda), but to their use in a treatment step. In other words, the claims do not just recite a natural relationship, but instead use the natural law or phenomenon in the treatment.
 Vanda Pharmaceuticals Inc. v. West-ward Pharmaceuticals International Limited, 887 F.3d 1117 (Fed. Cir. 2018).
 Rapid Litig. Mgmt. Ltd. v. CellzDirect, Inc., 827 F.3d 1042 (Fed Cir. 2016).
 Ariosa Diagnostics, Inc. v. Sequenom, Inc., 788 F.3d 1371 (Fed. Cir. 2015).
 Slip Op. at 6.
 Slip Op. at 7.
 Slip Op. at 7.
 Slip Op. at 7-8.
 Slip Op. at 11. The Federal Circuit acknowledged that the District Court did not have the advantage of considering the Vanda decision. Indeed, a June 7, 2018 memo from Robert W. Bahr to the Patent Examining Corps highlighted in the Vanda case several points which were emphasized in evaluating patent eligibility: (1) claims must be evaluated as a whole; (2) method of treatment claims which apply natural relationships (as opposed to being directed to them) were not analogous to Mayo.
 Slip Op. at 12.
 Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC, 915 F.3d 743 (Fed. Cir. 2019).
 Slip Op. at 15-16.
 Slip Op. at 16-17.
 Slip Op. at 15.
 Slip Op. at 15.
 Slip Op. at 12.
 Slip Op. at 17.
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