Monday, September 28, 2015

Magistrate Judge Finds Drug Method of Treatment Claim Patent Ineligible in Endo Pharmaceuticals v. Actavis

In 2009, I filed an amici brief on behalf of myself and several other law professors in Prometheus v.  Mayo, which was the first time the Federal Circuit heard the case.  In the decision below, the district court held that the interaction of a synthetic, non-naturally occurring pharmaceutical compound with the human body is a “natural phenomenon.”  In our brief, we basically argued that the interaction of a synthetic compound with the human body is not a natural phenomenon, but that if the definition of “natural phenomena” is interpreted so broadly as to encompass the interaction of human-made drugs with the human body, then by implication drug method of treatment claims seemed vulnerable to invalidation under 101 for encompassing patent ineligible subject matter.

Nonetheless, the Federal Circuit and the Supreme Court invalidated the Prometheus claims based on an assumption that the interaction of the pharmaceutical agent (the metabolic breakdown product of a drug) with the human body is a natural phenomenon.  In the Supreme Court’s decision, Mayo v. Prometheus, Justice Breyer seemed cognizant of this concern, and affirmatively stated that drug method of treatment claims should not be threatened by the holding in Mayo.  Still, I have continued to wonder how secure drug method of use claims are post-Mayo, particularly given the expansive interpretation of the Mayo/Alice by the district court’s and the Federal Circuit in decisions such as Ariosa (discussed in a previous post).

Thus, it came as no surprise when I saw a September 23, 2015 Report and Recommendation from a magistrate judge in the District of Delaware recommending invalidation of a drug method of treatment patent for patent ineligibility on a motion to dismiss under Rule 12(b)(6).  The case, Endo Pharmaceuticals v.  Actavis, is an ANDA litigation brought by Endo Pharmaceuticals against Actavis in connection with a Generic Oxymorphone ER Tablets.   The Report and Recommendation is available here.
The patent is US Patent Number 8,871,779, and representatives of claim one recites:

1. A method of treating pain in a renally impaired patient, 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

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 patient, the average AUC of oxymorphone over a 12-hour period is less than about 21 nghr/mL.

The magistrate judge applied the Mayo/Alice two-part test for patent eligibility.  The first step is to determine whether the claims at issue are “directed to a patent-eligible concept,” in this case a natural law.  The magistrate judge notes that the “Mayo court provided a broad definition for a law of nature: ‘[a] patent that… describes a relationship that is the consequence of entirely natural processes sets forth a natural law.’”  The judge went on to conclude that “the connection between the severity of renal impairment and the bioavailability of oxymorphone” was the relevant natural law to which the claims are directed.

The second step is to determine whether the claims “add enough” to the “natural law” to render the claim patent eligible.  The magistrate judge essentially determined that the “providing,” “measuring,” and “administering” steps were analogous to the steps in the claims held to be patent ineligible in Mayo, and thus did not provide “enough” extra. 

The claims at issue in Mayo essentially recited a method of performing a diagnostic test and determining the optimal dosage of drug for a patient.  The claim did not recite a step of actually administering the optimized dosage to a patient, and many have held out the hope that in the future a claim that included this additional step of actually applying the information derived from the diagnostic test would be found patent eligible.

But note that Endo’s claim does expressly recite administering a lower dosage of drug to a patient based on the results of the diagnostic test, i.e., the claim does include the extra step that many thought would have rendered the claims in Mayo patent ineligible.  But, at least in the view of this magistrate judge, the inclusion of this extra step was not sufficient to render the claim patent eligible.  And given the sweeping language of Mayo, particularly as interpreted by the Federal Circuit in Ariosa, it is not hard to see how the magistrate judge came to this conclusion.

It is important to note that the Endo claim is not a straightforward method of treatment claim, i.e., “a method of treating disease X by administering drug Y,” and does not necessarily indicate that the magistrate judge would have ruled such a claim patent ineligible.  The decision does explicitly note that “oxymorphone is ‘widely used’ for acute and chronic pain relief, the showing that the utilization of oxymorphone is not the invention.”  Thus, the magistrate judge seemed to imply that in a case where the “invention” is the discovery of a new pharmaceutical agent for the treatment of some medical condition a method of treatment claim could still be patent eligible under Mayo. 

It seems inevitable that before long we will be seeing a decision involving an allegation that a more conventional method of treatment claim is patent ineligible.  It will be interesting to see how the courts handle that case, and also how the district court judge in Endo v. Actavis (and perhaps the Federal Circuit eventually) responds to the magistrate judge’s recommendation.

Tuesday, September 22, 2015

Amgen Sues Hospira, Claims That Biosimilar Version of Epogen Infringes

In Amgen v. Sandoz, a fractured panel of the Federal Circuit held that an applicant seeking approval of a biosimilar under the abbreviated BPCIA pathway is not required to participate in the so-called “patent dance,” and that if a biosimilar applicant fails to provide the reference product sponsor with its application and the other patent dance information, then the reference product sponsor’s only recourse is to bring a declaratory judgment action for patent infringement.
On September 18, Amgen did just that, filing a lawsuit against Hospira alleging that Hospira’s planned marketing of a biosimilar version of Amgen’s biologic Epogen (epoiten alfa) infringes Amgen patents.   The complaint is available here. 

Amgen states that this “is one of the first actions for patent infringement under 35 USC 271(e)(2)(C), which was enacted in 2010 as part of the” BPCIA.
According to the complaint, Hospira submitted its Biologic License Application (BLA) under the expedited subsection (k) pathway, relying on Amgen’s demonstration of the safety and efficacy of Epogen, but has failed to comply with the patent provisions of the BPCIA.  For example, Hospira has not provided Amgen with manufacturing information that “would have given Amgen the opportunity to evaluate the manufacturing processes used by Hospira to determine whether those processes would infringe any patents held by Amgen.”  This is essentially the same complaint Amgen had with respect to Sandoz's application for expedited approval of a biosimilar filigrastim based on Amgen’s Neupogen product.
Amgen is also seeking a declaratory judgment that Hospira is required to provide Amgen with legally effective notice of commercial marketing of its biosimilar product, and information describing the processes or products used to manufacture the biosimilar product.  In Amgen v. Sandoz, the Federal Circuit held that a biosimilar applicant must provide notice to the reference sponsor on or after the date that the FDA approves its biosimilar application, but according to the complaint Hospira has refused to do so.


Tuesday, September 1, 2015

Rapid Litigation Management (Celsis) v. Cellzdirect: BIO Files Amicus Brief in Another Patent Eligibility Case before the Federal Circuit

On August 28, 2015, the Biotechnology Industry Organization (BIO) filed an amicus brief in another important patent eligibility case currently before the Federal Circuit, Rapid Litigation Management (formerly Celsis In Vitro) v. Cellzdirect.  The claims at issue are directed towards a "method for freezing hepatocytes multiple times without further significant loss of cell health and viability."  The method has three steps: (1) previously frozen cells are thawed, (2) nonviable cells are separated from viable ones using a “density gradient fractionation,” and then (3) viable cells are cryopreserved for later use.  In the decision below, the District Court invalidated the claims, finding them to be directed towards patent ineligible subject matter.
In applying the first step of the Mayo two-step test for patent eligibility, the District Court found that the “patent is directed to an ineligible law of nature: the discovery that hepatocytes are capable of surviving multiple freeze-thaw cycles.”  In the second step, the court found the claimed method to lack sufficient “inventive concept,” because claimed elements such as freezing cells and the use of density gradient fractionation were found to be “well understood.”

In its brief, BIO urges the Federal Circuit to clarify the boundaries regarding the scope of the term “law of nature,” and argues that hepatocytes are not subject to repeated freezing in nature under the conditions of the claimed methods, and thus that the claim does not implicate a law of nature.  The brief also argues that the district court’s approach, which essentially “requires an undefined ‘something else,’ that cannot be satisfied by the application of known techniques and reagents to a newly recognized natural phenomenon, threatens the availability of patent protection for a host of important innovations spanning the length and breadth of biotechnology.”

BIO also argues that “[b]ecause of its well-developed record on the non-obviousness of the claimed invention, this case may present a good opportunity for this court to clarify the interplay between Section 103 and Step II of the Mayo/Alice framework."