Establishing a General Premise Does Not Satisfy the High Burden of Proving an Inherent Disclosure of a Claimed Feature under an Obviousness Rejection
Bernadette McGann | December 22, 2014
Par Pharmaceutical, Inc. v. TWI Pharmaceuticals, Inc.
December 3, 2014
Panel: O’Malley, Wallach, and Hughes. Opinion by O’Malley.
Patent 7,101,576 (hereinafter ‘576) is directed towards a method of using megestrol nanoparticles to increase the body mass in a human patient suffering from wasting.
The CAFC vacated a District Court judgment of invalidity of the ‘576 patent and remanded for further analysis. The CAFC held that the District Court committed an error since the District Court analysis of inherency ignored the specific claim limitations at issue.
Megestrol is used to treat wasting, specifically for the treatment of anorexia and cachexia in AIDS patients. Bristol-Myers Squibb marketed Megace OS, a micronized megestrol oral suspension. Par Pharmaceutical developed a nanosized megestrol formulation, which was marketed as Megace ES. “Patients taking Megace OS with a meal showed a significantly higher rate and extent of absorption compared with those patients who took Megace OS while in a fasting state. The nanosized megestrol formulation, however, showed a greatly reduced food effect. A reduction in the food effect would be especially vital for AIDS patients undergoing wasting, as those patients often have substantially reduced appetites.” See page 3.
Claim 1 of the ‘576 patent recites:
1. A method of increasing the body mass in a human patient suffering from anorexia, cachexia, or loss of body mass, comprising administering to the human patient a megestrol formulation, wherein:
(a) the megestrol acetate formulation is a dose of about 40 mg to about 800 mg in about a 5 mL dose of an oral suspension;
(b) the megestrol acetate formulation comprises megestrol particles having an effective average particle size of less than about 2000 nm, and at least one surface stabilizer associated with the surface of the megestrol particles; and
(c) the administration is once daily;
wherein after a single administration in a human subject of the formulation there is no substantial difference in the Cmax of megestrol when the formulation is administered to the subject in a fed versus a fasted state,
wherein fasted state is defined as the subject having no food within at least the previous 10 hours, and wherein fed state is defined as the subject having a high-calorie meal within approximately 30 minutes of dosing.
(Emphasis added to the claimed feature at issue before the CAFC) Dependent claim 4 further defines the Cmax of megestrol feature.
Par Pharmaceutical, owners of the ‘576 patent, filed suit against TWi for infringement, shortly after TWi filed an ANDA with the FDA, seeking approval to market a generic form of nanosized megestrol. TWi responded that the claims of the ‘576 patent were obviousness under §103, do not cover patentable subject matter under §101, were not enabled and Par does not have standing to assert its claims. After a bench trial, the District Court concluded that the ‘576 patent was invalid as obvious.
The District Court held that “TWi showed megestrol acetate was a known BCS Class II drug with poor bioavailability, TWi failed to prove that Megace OS had a known bioavailability problem or a known food effect in the prior art…TWi proved that all elements of the claimed invention were disclosed in the prior art…. Importantly, even though the prior art did not explicitly disclose the food effect differences as claimed, the district court concluded that ‘[t]he claimed pharmacokinetic parameter with respect to a food effect …are inherent properties of the obvious nanoparticulate formulation.’ The reduced food effect was thus ‘an inherent result’ of nanosized megestrol ‘even if it was previously not known in the prior art that a food effect existed’.” See pages 9-10.
The issue before the CAFC is whether TWi carried its burden of proving that all of the claim limitations of the ‘576 patent were disclosed in the prior art. TWi asserted, and the District Court concluded, that the specific food effect limitations of the ‘576 patent were inherent properties of the formulation disclosed by the obvious combination of the prior art.
A party asserting that a patent is obvious “must ‘demonstrate by clear and convincing evidence that a skilled artisan would have had reason to combine the teaching of the prior art references to achieve the claimed invention, and that the skilled artisan would have had a reasonable expectation of success from doing so.’” In re Cyclobenzaprine Hydrochloride Extended-Release Capsule Patent Litig., 676 F.3d 1063, 1068-69 (Fed. Cir. 2012) (quoting Procter & Gamble Co. v. Teva Pharm. USA, Inc., 566 F.3d 989, 994 (Fed. Cir. 2009)
Inherency may supply a missing claim limitation in an obviousness analysis. See e.g., Santarus, Inc. v. Par Pharm., Inc., 694 F.3d 1344, 1354 (Fed. Cir. 2012); Alcon, 687 F.3d at 1369; In re Kao, 639 F.3d 1057, 1070 (Fed. Cir. 2011); In re Kubin, 561 F.3d 1351, 1357 (Fed. Cir. 2009).
Inherency, however, may not be established by probabilities or possibilities. The mere fact that a certain thing may result from a given set of circumstances is not sufficient. If, however, the disclosure is sufficient to show that the natural result flowing from the operation as taught would result in the performance of the questioned function, it seems to be well settled that the disclosure should be regarded as sufficient. In re Oelrich, 666 F.2d 578, 581 (CCPA 1981) (emphasis added).
“[T]he concept of inherency must be limited when applied to obviousness, and is present only when the limitation at issues is the ‘natural result’ of the combination of prior art elements. Id.” See page 15.
“A party must, therefore, meet a high standard in order to rely on inherency to establish the existence of a claim limitation in the prior art in an obviousness analysis – the limitation at issue necessarily must be present, or the natural result of the combination of elements explicitly disclosed by the prior art.” See page 16.
The CAFC held that the District Court did not commit any error in concluding that there was no known food effect for megestrol in the prior art. However, the District Court did commit a clear error because its inherency analysis of the claimed food effect feature was flawed.
During the bench trial, TWi presented evidence establishing that a reduction in particle size improves bioavailability and TWi’s expert testified that “an improvement in bioavailability ‘necessarily results in a decrease in any food effect.’” The District Court held “the reduced particle size would, ipso facto, lead to a reduced food effect.
The CAFC vacated and remanded the District Court holding because the District Court’s analysis fails to take into consider the specific claim limitations of the ‘576 patent. The CAFC noted that the District Court’s analysis does not address the “no substantial difference in Cmax” between the fed and fasted states feature and does not address the “difference in Cmax” feature. “While it may be true that a reduction in particle size naturally results in some improvement in the food effect, the district court failed to conclude that the reduction in particle size naturally results in ‘no substantial difference’ in the food effect.” See pages 16 and 17.
Evaluate the inherency assertion in relation to the specific claim language presented. Do not allow the courts or the U.S. PTO to present a broad generalization regarding an allegedly inherent claim feature.
During patent prosecution, in order to overcome an inherency assertion, it is the Applicants’ burden to establish that the cited art does not inherently possess the claimed feature, as asserted by the Examiner. “The PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his [or her] claimed product.” See MPEP §2112. This may be accomplished by establishing various factors that would affect the allegedly inherent feature.