The Federal Circuit’s May decision in In re Kao caught the attention of the patent prosecution community in general, and those of us working in pharma in particular, because it seemed to give some more contours to the obviousness doctrine post-KSR. The decision involved three patent applications, all of which relate to aspects to Endo’s Opana ER®, a commercially successful extended-release version of the opioid narcotic oxymorphone. The Board of Patent Appeals and Interferences (BPAI) had rejected all three applications on grounds of obviousness; the CAFC reversed and remanded in one application (11/680,432) and sustained the Board’s rejections in the other two cases (12/167,859 and 11/766,740).
It was the decision in the ‘432 application that grabbed the headlines. Among other things, the CAFC said that it was wrong for the PTO to say that the dissolution profile recited in the claims of that application was obvious in view of the Maloney reference (WO 01/08661), since Maloney disclosed determining the dissolution profile using a test which was different from the test recited in the claims, and there was no evidence that the two tests were equivalent. Interested readers can check the summaries in PatentDocs and PatentlyO for more information.
What doesn’t seem to have attracted widespread attention, but did catch the eye of Endo’s attorneys (Jeff Lewis et al.), was the Board’s treatment of the ‘859 application and the CAFC’s upholding of that decision, in particular its application of the inherency doctrine. Under the CAFC’s case law, this doctrine says that even if no one appreciated what the prior art taught, the fact that a product or process was inherent in the prior art means that the thing now being claimed is not new.
The CAFC’s 2003 Schering v Geneva Pharmaceuticals decision provides a reasonable illustration of this doctrine. In that case, the one and only claim of Schering’s patent application, a claim directed to a particular chemical chemical compound, was found to lack novelty: it was undisputed that the claimed compound, a metabolite, was formed in the human body whenever a person ingested a different, known compound, and that ingestion of that different, known compound by people had been taught in the prior art. Thus, despite that fact that before Schering, no one had actually identified the metabolite, the claimed compound per se was inherently disclosed by the prior art (since the prior art taught how to make the compound – just administer the precursor compound to a person) and therefore the claim on the compound per se lacked novelty. In that decision, the CAFC noted that Schering could have secured protection had its claims been worded differently, for example if it had claimed the compound in solid form or substantially pure form, neither of which were inherently disclosed by the prior art.
Inherency is thus a basis for making a novelty rejection against a claim. In contrast, a claim rejection on grounds of obviousness requires that, at the time that the invention was made, the claimed invention was obvious to one skilled in the art on the basis of the prior art. Thus whereas a novelty rejection merely requires that the claimed thing existed, even if no one appreciated that existence – and therefore such a rejection can be based on grounds of inherent prior disclosure – an obviousness rejection requires that one of skill in the art appreciated what the prior art taught. Without such appreciation, the claimed invention could not have been obvious at the time it was made.
Inherency came into play in that the claims at issue in the ‘859 application, claims 8 and 21, were found to be obvious – not anticipated – because a property recited in the claims was deemed to be an inherent property of oxymorphone. Claim 8 reads,
8. A method for treating pain in a human subject in need of acute or chronic pain relief, comprising the steps of:
(a) providing a solid oral dosage form comprising about 5 mg to about 80 mg oxymorphone or a pharmaceutically acceptable salt thereof in a controlled release delivery system with a release rate profile designed to provide an adequate blood plasma level over at least 12 hours to provide sustained pain relief over this same period, the system comprising a filer and a hydrophilic material, wherein oxymorphone is the sole active ingredient; and,
(b) administering the dosage form to the subject, wherein the oxymorphone Cmax is at least about 50% higher when the dosage form is administered to the subject under fed versus fasted conditions.
It’s the last, emphasis-added clause which is critical.
The only art relied upon by the BPAI and the CAFC in rejecting claim 8 was Maloney. Both the USPTO and Endo agreed that Maloney does not actually teach that there is a different release profile for oxymorphone, or any other opioid, when the drug is administered to a fed patient versus when it is administered to a fasting patient. And it’s uncontested that prior to the disclosure of this fact in Endo’s own patent application, one of skill in the art would not have recognized this different release profile. Nevertheless, the CAFC found that this property was an inherent property of oxymorphone itself, and that since Maloney made it obvious to make and administer the composition recited in claim 8, the claimed method was obvious. As explained by the CAFC,
The examiner rejected claims 8 and 21 as obvious in view of, among other references, Maloney. The examiner found that Maloney "teaches oral sustained release preparations of opioid analgesics" with the use of oxymorphone as a preferred opioid.
On appeal, the Board affirmed the examiner's rejection, relying exclusively on Maloney. The Board found that Maloney discloses a controlled release formulation with an opioid in amounts of 5- 100 mg and that oxymorphone is a preferred opioid. The Board found that Maloney further teaches using calcium sulfate (a cross linking agent), lactose (a filer), and hydrogenated vegetable oil (a hydrophobic material) in his formulation. Based on these disclosures, the Board determined that it would have been obvious to a person of ordinary skill in the art to formulate the claimed oral dosage form and to administer the form to the subject as claimed in the '859 Application.
* * *
Endo argues that Maloney does not expressly disclose the "food effect" limitation: "wherein the oxymorphone Cmax is at least about 50% higher when the dosage form is administered to the subject under fed versus fasted conditions." Endo asserts that the Board erroneously relied on the teaching in the specification of the '859 Application that the claimed "food effect" was a property of oxymorphone and that Maloney inherently disclosed the limitation. Endo argues that an obviousness rejection can only be based on what is known by those of skill in the art at the time of the invention, and there is no evidence in the record that anyone recognized the claimed food effect at that time.
The Office responds that substantial evidence supports the Board's finding of inherency. The Office further responds that the Board's reliance upon the specification of the '859 Application to support this conclusion is entirely proper. Further, the Office responds that inherency is indeed a part of the obviousness inquiry.
This court agrees with the Office. Substantial evidence supports the Board's finding, based upon the specification, which confirms that the claimed "food effect" is an inherent property of oxymorphone itself, present both in controlled release and immediate release formulations of that drug. See In re Kubin, 561 F.3d 1351, 1357 (Fed. Cir. 2009) (stating "(e)ven if no prior art of record explicitly discusses the (limitation), (applicant's) application itself instructs that (the limitation) is not an additional requirement imposed by the claims on the (claimed invention), but rather a property necessarily present in (the claimed invention)"); see also King Pharmaceuticals, Inc. v. Eon Labs, Inc., 616 F.3d 1267, 1275-76 (Fed. Cir. 2010) (stating that "merely discovering and claiming a new benefit of an old process cannot render the process again patentable" (citations omitted)). This is not a case where the Board relied on an unknown property of prior art for a teaching. Rather, Maloney's express teachings render the claimed controlled release oxymorphone formulation obvious, and the claimed "food effect" adds nothing of patentable consequence.
[emphasis added]
In a petition for rehearing and en banc filed on June 23, Endo asserts that in dealing with Endo’s ‘859 application, the BPAI decision, and subsequently, the CAFC panel (Judges Linn, Moore and Rader) expanded the scope of the inherency doctrine to include not only anticipation but obviousness as well, in contrast to well-settled case law, the patent statute itself, and good public policy.
In its petition, Endo argues that the BPAI and the CAFC erred, in that (a) the claim is not directed to a pharmaceutical composition per se, but to a method of treatment, (b) all parties agree that the “food effect” was not in the prior art and would not have been recognized by one of skill in the art prior to the applicants’ own disclosure of that effect, and therefore (c) in accordance with the CAFC’s own precedent, the claimed method cannot be deemed obvious, since inherency applies only with respect to novelty analyses, not obviousness analyses.
As the petition for rehearing notes, if the inherency doctrine is expanded to encompass obviousness as well, then
“The Panel's decision would bar claiming a new method of treatment using a known medicine (e.g., discovering that the proverbial cure for cancer is a new use of an old compound). Even if the use is novel and not what is expected by those of ordinary skill in the art at the time, the Panel decision would render it unpatentable because the effect would be inherent in the compound's use; although beneficial and previously unknown, the use would be deemed "inherent" to the compound.”
That’s clearly not a desirable result, and as the request notes, it’s a result that’s contrary to the constitutional mandate of promoting “the Progress of … useful Arts”.
The petition also argues that under CAFC case law, obviousness, per 35 U.S.C. §103, is a question that must be decided with regard to the claimed subject matter as a whole, on the basis of what was understood by persons skilled in the art at the time the invention was made, and that prior to Endo’s own disclosure in the subject patent application, no one had taught or suggested that administering an oxymorphone sustained release formulation to a fed patient could yield significantly better results than administering the formulation to a fasting patient. The request also explains why the cases relied upon by the CAFC in its decision do not support its position.
With regard to the application of the inherency doctrine, Endo’s arguments are compelling. Suppose a compound is known for treating headaches; now it’s found that it can also be used as a chemotherapeutic agent. But those anti-cancer properties are an inherent property of that compound, so under the CAFC’s logic in Kao, the fact that prior art taught administering the compound to a person, coupled with this inherent chemotherapeutic property, means that it was obvious to use the drug for chemotherapy – even though in point of fact it wasn’t obvious to anyone. At any rate, apparently the USPTO thinks enough of this argument that it warrants further study – it has asked for an received an extension until August 12, 2011 to file its response to the petition for rehearing.
Where I wonder about the propriety of Endo’s argument is not with regard to its observation about the proper scope of the inherency doctrine, but with regard to whether or not the doctrine has been misapplied with respect to the particular claims at issue, claims 8 and 21 of the ‘859 application. That’s because although the “food effect” is recited in both claims, it’s open to interpretation if the recitation of the “food effect” constitutes a method step. Suppose we left the “food effect” recitation out of claim 8. Then it would read,
8. A method for treating pain in a human subject in need of acute or chronic pain relief, comprising the steps of:
(a) providing a solid oral dosage form comprising about 5 mg to about 80 mg oxymorphone or a pharmaceutically acceptable salt thereof in a controlled release delivery system with a release rate profile designed to provide an adequate blood plasma level over at least 12 hours to provide sustained pain relief over this same period, the system comprising a filer and a hydrophilic material, wherein oxymorphone is the sole active ingredient; and,
(b) administering the dosage form to the subject.
In this instance, the argument for the obviousness of the claimed method on the basis of Maloney is much stronger, since Maloney teaches similar compositions using opioid analgesics (albeit not oxymorphone itself) and their administration to relieve pain. If the clause “wherein the oxymorphone Cmax is at least about 50% higher when the dosage form is administered to the subject under fed versus fasted conditions“ is viewed not as reciting a method step, but merely reciting what is an inherent property of the composition itself, then as the CAFC noted, that recitation doesn’t add patentable weight to the claim.
Personally I’d feel that Endo was on better grounds had it recited the “food effect” limitation in part (a), as a functional feature along with the structural features of the composition being administered, for example,
8. A method for treating pain in a human subject in need of acute or chronic pain relief, comprising the steps of:
(a) providing a solid oral dosage form comprising about 5 mg to about 80 mg oxymorphone or a pharmaceutically acceptable salt thereof in a controlled release delivery system with a release rate profile designed to provide an adequate blood plasma level over at least 12 hours to provide sustained pain relief over this same period, the system comprising a filer and a hydrophilic material, wherein oxymorphone is the sole active ingredient, and wherein the oxymorphone Cmax is at least about 50% higher when the dosage form is administered to the subject under fed versus fasted conditions; and,
(b) administering the dosage form to the subject.
Here, since the fasted-vs.-fed release profile is recited as one of the limitations on the compositions that can be used in accordance with the claimed invention, it’s easier to assert that this limitation is part of the claimed method (though not a slam-dunk). An even better route would have been to recite administering the composition to a patient within (or not within) a certain amount of time in relation to eating. The prescribing information for OpanaER® says that it should be administered “on an empty stomach, at least 1 hour prior to or 2 hours after eating”. If such a recitation had been included in the claim 8, it clearly would have been part of the claimed method, not taught or suggested in the prior art, and, as Endo notes, therefore not subject to a finding of inherency.
Given the way the CAFC not once but twice bent over backward to construe the claims in Prometheus v Mayo as actually reciting a process, it’s possible that here too, if rehearing en banc is granted, the court will deem the last “wherein” clause of claim 8 to recite a process limitation. In any event, I hope the CAFC takes this opportunity to correct itself and clarify the applicability of the inherency doctrine. The way the panel decision is worded, Endo is right about this spelling the end of second medical use patents.