Endo Pharmaceuticals Inc. v. Actavis Inc. (D. Del. 2015)

District Court Adopts Magistrate's Conclusion of Invalidity under § 101 and Grants Defendants' Motion to Dismiss Counts

By Donald Zuhn --

Last month, in Endo Pharmaceuticals Inc. v. Actavis Inc., Judge Richard G. Andrews of the U.S. District Court for the District of Delaware adopted Magistrate Judge Mary Pat Thynge's conclusion that U.S. Patent No. 8,808,737 was facially invalid under 35 U.S.C. § 101 because it is directed to patent-ineligible subject matter and, following the Magistrate's recommendation, granted Defendants' motion to dismiss certain counts.  The '737 patent, which is assigned to Endo Pharmaceuticals Inc., is directed to methods of using oxymorphone to treat pain in patients with renal impairment.  Representative claim 1 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 m[L]/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 ng•hr/mL.

Plaintiffs Endo Pharmaceuticals Inc. and Mallinckrodt LLC filed suit against Defendants Actavis Inc. and Actavis South Atlantic LLC, asserting that Defendants infringed the '737 patent by manufacturing, offering for sale, or selling their generic Oxymorphone ER tablets and by submitting an ANDA to the FDA.  Defendants moved to dismiss counts I, III, and IV of Plaintiffs' complaint pursuant to Fed. R. Civ. P. 12(b)(6), arguing that the '737 patent was facially invalid under 35 U.S.C. § 101 because it is directed to patent-ineligible subject matter.

On September 23, the Magistrate issued a Report and Recommendation regarding Defendants' motion, recommending that the District Court grant the motion.  Noting that resolution of Defendants' motion depends on whether representative claim 1 of the '737 patent is directed to patent-ineligible subject matter under § 101 or is a patent-eligible application of a law of nature, the Magistrate applied the two-step analysis set forth in Mayo Collaborative Servs. v. Prometheus Labs., Inc., 132 S. Ct. 1289 (2012), and reiterated in Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347 (2014).  With regard to the first step, the Magistrate indicated that:

Here, defendants repeatedly point out that the '737 Patent attempts to cover the natural law that the "bioavailability of oxymorphone is increased in people with impaired kidney function."  Indeed, plaintiffs effectively concede the first step of the Mayo analysis.  They suggest though, that the invention is not related to the natural law, but is a "novel and useful application of that discovery -- i.e., to the treatment of renally impaired patients by administering a lower dose of oxymorphone based upon the severity of the renal impairment."  The '737 Patent, however, explains that oxymorphone is "widely used" for acute and chronic pain relief, thus showing that the utilization of oxymorphone is not the invention.  Therefore, the connection between the severity of renal impairment and the bioavailability of oxymorphone, which the '737 Patent sets forth in detail, is the subject matter of the invention.

With regard to the second step of the Mayo/Alice analysis, the Magistrate began by examining each individual step of the claim and then looking at the claim as a whole.  According to the Magistrate's Report, claim 1 consists of three steps: (1) a "providing" step; (2) a "measuring/determining" step; (3) and an "administering" step.

With respect to the "providing" step, the Magistrate found this step insufficient to make the claim patentable, stating that the step "simply informs patients and prescribing physicians of the relevant drug to be administered," and noting that "[t]his step is similar to the 'administering' step in Mayo because it merely identifies the specific drug for administration."  The Magistrate also noted that the '737 specification admits that extended-release oxymorphone had been available on the market, and that oxymorphone was widely used in the treatment of acute and chronic pain.  The Magistrate also determined that the "measuring/determining" step "suffers from similar deficiencies," noting that the step "only instructs the physician to measure the patient's creatinine level to determine the level of renal impairment using a previously recognized method."  As to the "administering" step, the Magistrate noted that this step:

[S]imply limits the relevant audience to patients and prescribing physicians, who treat chronic or acute pain with oxymorphone, 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."

Finally, when analyzing the claim as a whole, the Magistrate concluded that "the steps in combination do not transform the natural law into a patentable application of that law."  In response to the Plaintiffs' argument that the administering step turns the natural law recited in the claim into a patentable application, the Magistrate countered that the administering step "merely instructs physicians to dispense oxymorphone for the treatment of pain in a well-know[n] manner, while utilizing the natural law to manage the dosage," adding that "the '737 Patent recognizes the use of oxymorphone for pain relief is a well-understood activity."  In recommending that Defendants' motion to dismiss be granted, the Magistrate concluded the Report by suggesting that:

[I]t is inevitable that a doctor may infringe [claim 1 of the '737 patent] by checking a patient's creatinine level to determine renal impairment (as it is known in the medical field that renal impairment affects the bioavailability of certain drugs) and lowering the dosage of oxymorphone in response to the lab test findings.

In his Order Adopting Report and Recommendation, Judge Andrews addressed Plaintiffs' arguments that the Magistrate erred in finding the '737 patent to be facially invalid under § 101 and recommending that Defendants' motion to dismiss be granted.  With respect to the Magistrate's emphasis on the factual similarity between representative claim 1 of the '737 patent and the representative claim at issue in Mayo, Judge Andrews stated that "[b]ecause the claim limitations at issue in Mayo do in fact mirror the analogous limitations of Claim 1 of the '737 patent, I think it was correct for the Magistrate Judge to do so."  Judge Andrews also found Plaintiffs' argument that the '737 patent does not claim a law of a nature, but rather claims a new and useful process, to be "thoroughly unconvincing," adding 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."

In overruling Plaintiffs' objections to the Magistrate's Report and Recommendation, and granting Defendants' motion to dismiss, Judge Andrews concluded by expressing his "disagree[ment] with Plaintiffs' policy argument that the Magistrate Judge's reasoning is so far-reaching that it would invalidate all pharmaceutical method-of-treatment patents that employ an existing pharmaceutical compound."  He suggested that:

Patentees can still avoid invalidation under § 101 by demonstrating an inventive leap beyond merely claiming a law of nature.  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 the 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.

Comments

[EG]

"Oxymorphone (Opana, Numorphan, Numorphone) or 14-Hydroxydihydromorphinone is a powerful semi-synthetic opioid analgesic (painkiller) first developed in Germany in 1914,[2] patented in the USA by Endo Pharmaceuticals in 1955[3] and introduced to the United States market in January 1959 and other countries around the same time."

Don,

From Wikipedia. Another "poster child" case for why the holding in Mayo is utter nonsense and factually dishonest. Like the drug being administered in Mayo, the drug being administered here is SYNTHETIC, and therefore cannot be a "law of nature." When will the judiciary, and especially the Royal Nine, come to their senses, and admit that the holding in Mayo based upon patent-eligibility is wrong? These cases should be judged under 35 USC 102/103/112, not 35 USC 101.

[Nandy]

the '737 Patent attempts to cover the natural law that the "bioavailability of oxymorphone is increased in people with impaired kidney function."

Hey EG,

Endo is not trying to get patent protection for synthetic Oxymorphone, instead to monopolize a result of a routine metabolic process of everyone's body.

By just testing your blood and telling you 'hey you need to cut down your sugar intake as you are diagnosed as hyperglycemic' won't qualify for invention.

[EG]

"Endo is not trying to get patent protection for synthetic Oxymorphone, instead to monopolize a result of a routine metabolic process of everyone's body."

Hey Nandy (aka MM, and assorted other pseudonyms),

You (like Breyer and the rest of the Royal Nine) completely missed the relevant point: because the drug is synthetic, the method involving it cannot be a "law of nature," therefore cannot be patent-ineligible under 35 USC 101. Whether this method is patentable as being unobvious under 35 USC 103 is what is relevant and an entirely different matter.

And whether you (or the Royal Nine) agree with my position matters not one iota to me.

[skeptical]

The "logic" of:

"instead to monopolize a result of a routine metabolic process of everyone's body."

if applied on its face RULES OUT every single pharma patent.

Every single one.

Even the non-method composition patents.

Why the composition ones? Well, to see that, one just as to remember that a 101 condition is utility. Without this "natural law," every pharma patent will fail for lacking utility. Even the composition ones become a Breyer-like trap of "just apply it." Remove the utility and you fail 101 every bit as if you fail to place your invention into any one of the (broad) statutory categories.

This is an EASY take-away from ALice, in which case it was stipulated (and unquestioned, thus NOT before the Court) that the invention included that which SATISFIED a statutory category aspect of 101**.

Critical thinking on the Supreme Court power trip reveals that they have NULLIFIED the statutory categories -the exceptions as written (poor scriviners as they are), are left to swallow the actual law written by Congress.

**I would note as well that there were claims that satisfied BOTH the statutory category aspect AND the utility aspect - the only two real aspects in the law of 101 as written by Congress, but that's a different point.

[The Memory Motel]

skeptical: "f applied on its face RULES OUT every single pharma patent."

Of course that's false but it's part of your easy-to-remember script so we understand why you can't help yourself.

Nandy has the right analysis. There's no point in addressing Guttag since the guy has been off-the-rails since the Supremes too away his lollipop in Prometheus.

[skeptical]

Malcolm, aka host of sockpuppets, I would reply to you if I could find some point to which to reply to.

As it is, all you present is ad hominem.

Please have a little more respect for this forum.

[Erik]

Won't lots of substances have higher concentrations in the bloodstream, and reach the site of action, if the kidneys don't eliminate them? So the man-made nature of oxymorphone really has nothing to do with the bioavailability as measured by absolute AUC. It is a natural property of the failure of the kidneys to properly eliminate substances. This is like arguing that oxymorphone is infiniately patentable because it is man-made and has mass, so the fact that it changes weight in different gravitational environments is a man-made result. (After all, you could put it in a sack and use it as a paperweight).