United States: For Obviousness, A Motivation To Combine Does Not Require A Suggestion That The Claimed Combination Is Preferred Or Most Desirable

In Bayer Healthcare Pharmaceuticals, Inc. v. Watson Pharmaceuticals, Inc., Nos. 12-1397, -1398, -1400, -1424 (Fed. Cir. Apr. 16, 2013), the Federal Circuit reversed the district court's entry of SJ that asserted claims 13 and 15 of U.S. Patent No. RE37,564 ("the '564 patent") were not invalid for obviousness.

Bayer Healthcare Pharmaceuticals, Inc. and Bayer Schering Pharma AG (collectively "Bayer") own the '564 patent, directed to low-dose, extended-regimen combined oral contraceptive ("COC") products.  To address the risks of side effects, "escape" ovulation, and unintended pregnancy, Bayer developed a low-dose COC containing synthetic estrogen ethinylestradiol ("EE") and synthetic progestin drospirenone ("DRSP") administered according to a dosing regimen of either twenty-four active pills followed by four pill-free days (24/4) or twenty-three active pills followed by five pill-free days (23/5), as opposed to the traditional dosing regimen of twenty-one active pills followed by seven pill-free days (21/7).

Asserted claims 13 and 15 of the '564 patent cover Bayer's COC product, marketed under the brand name YAZ®.  Watson Pharmaceuticals, Inc., Watson Laboratories, Inc., Sandoz, Inc., Lupin Ltd., and Lupin Pharmaceuticals, Inc. (collectively "Defendants") filed ANDAs with the FDA seeking approval to market generic versions of YAZ® and asserting that the '564 patent was invalid.  Bayer responded by suing Defendants for infringement of claims 13 and 15 of the '564 patent, and Defendants counterclaimed that the asserted claims were invalid for obviousness.  The district court ultimately granted SJ in favor of Bayer, concluding that the asserted claims were not invalid for obviousness.  Defendants appealed.

On appeal, the Federal Circuit agreed with Defendants that the district court erred in concluding that asserted claims 13 and 15 were not invalid for obviousness.  The Court first observed that it was undisputed that the cited prior art set forth every limitation required by the asserted claims.

"[A] finding that the prior art as a whole suggests the desirability of a particular combination need not be supported by a finding that the prior art suggests that the combination claimed . . . is the preferred, or most desirable, combination."  Slip op. at 15 (alterations in original) (quoting In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004)).

The Court also found that the prior art provided express motivation for a person of ordinary skill in the art to combine the limitations to derive the claimed COC products with a reasonable expectation of success.  The Court noted that one prior art reference expressly referenced another, which together with the first disclosed every limitation of the asserted claims.  The Court also noted that several of the cited references highlighted evidence that unregulated ovarian activity occurring during a seven-day pill-free interval could achieve significant follicular development, and that those references expressed concern that inadvertently extending the traditional pill-free interval via one or more missed pills could lead to escape ovulation and unintended pregnancy.  The Court also reasoned that Bayer's expert acknowledged that one of skill in the art at the time of the invention would have expected an even greater risk of such "missed pill" ovulation for users of low-dose COCs.

The Court thus concluded that missed-pill ovulation was a recognized concern with traditional 21/7 COCs, particularly for those on the market by 1993 that, like the claimed COC preparations, relied on low-dose EE.  "As the Supreme Court has stated, 'any need or problem known in the field of endeavor at the time of invention and addressed by the patent can provide a reason for combining the elements in the manner claimed.'"  Slip op. at 13 (quoting KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 420 (2007)).  The Court further reasoned that the references went beyond just illuminating a known problem—they also expressly proposed the claimed solution.

The Court rejected Bayer's argument that two of the references were primarily directed to older women who reached premenopause and were in need of hormone replacement therapy such that a skilled person setting out to design an oral contraceptive using EE and DRSP would not have used the 24/4 regimen intended to achieve effective hormone replacement therapy.  The Court stated that those references plainly disclosed preparations with hormone replacement and contraceptive applications, and that the product claims-at-issue did not distinguish between target patient populations by age or otherwise.

The Court also rejected Bayer's argument that the prior art taught away from the claimed COC preparations, focusing on statements in the "Guillebaud" reference as indicating that the conventional wisdom in the field favored 21/7 dosing for most patients and as suggesting that a reduced pill-free interval should be used together with higher-dose COCs for patients perceived to be at risk of escape ovulation.  The Court reasoned that those statements did not overcome the express teachings of multiple references, including Guillebaud, that a shorter pill-free interval would improve COC efficacy.  Furthermore, the Court noted that Guillebaud may have suggested condensing the pill-free interval while concurrently increasing the hormone dose for at-risk patients, but those two measures were never described as mutually dependent, and each could be expected to reduce missed-pill ovulation risks with or without the other.  "[A] finding that the prior art as a whole suggests the desirability of a particular combination need not be supported by a finding that the prior art suggests that the combination claimed . . . is the preferred, or most desirable, combination."  Id. at 15 (alterations in original) (quoting In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004)).  The Court stated that just because one of several references indicated a preference for using 24/4 or 23/5 dosing regimens in tandem with higher-dose COCs did not mean the same missed-pill rationale could not also motivate applying the shorter pill-free interval to similarly improve other COC preparations.

Finally, the Court held that Bayer's evidence of secondary indicia of nonobviousness, including alleged unexpected results, expert skepticism, industry praise, and copying by others, was legally insufficient.  Regarding unexpected results, the Court found that data showing that 23/5 administration resulted in reduced follicular activity compared to 21/7 dosing of the same COC formulation merely confirmed that administering additional active pills resulted in additional follicular suppression, a matter of common sense.

Regarding expert skepticism, Bayer cited an FDA request for clinical safety data and data demonstrating efficacy benefits sufficient to justify the added synthetic hormone exposure required for the proposed 24/4 dosing regimen.  The Court found that that request in no way indicated FDA experts would have been surprised to receive such data, since the cited request reflected attention to the FDA's normal duties ensuring the safety and efficacy of new drugs by requiring actual data to corroborate statements in a new drug application.

Regarding industry praise, Bayer claimed that its invention was widely praised by experts in the COC field, relying on journal citations that referenced the findings stated in Bayer's published efficacy studies or discussed possible noncontraceptive indications for 24/4 COC regimens.  Bayer also relied on an article that was authored by the first-named inventor of the '564 patent describing Bayer's 24/4 COC regimen as an innovative strategy.  The Court found that the bare journal citations and self-referential recommendation fell well short of demonstrating true industry praise.  The Court also stated that industry praise of what was clearly rendered obvious by published references was not a persuasive secondary consideration.

Regarding copying by others, the Court rejected Bayer's contention that copying of its COC preparations by the defendants and other generic manufacturers supported its validity position, noting that such evidence of copying in the ANDA context was not probative of nonobviousness because a showing of bioequivalence was required for FDA approval.  Accordingly, the Court held that claims 13 and 15 of the '564 patent were invalid for obviousness in view of the cited references, and reversed the district court's SJ.

This article previously appeared in Last Month at the Federal Circuit, May, 2013

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