In Bayer Schering Pharma AG v. Lupin, Ltd., the Federal Circuit upheld the district court’s determination that the Abbreviated New Drug Applications at issue did not infringe the asserted patent related to Yasmin. In particular, the Federal Circuit agreed that the FDA had not approved Yasmin for the method of use claimed in the patent, and so filing the ANDAs could not amount to infringement of the patent.

While this case is similar to Caraco Pharmaceutical Labs., Ltd. v. Novo Nordisk A/S, in that it relates to a method of use patent in the ANDA framework, it raises different issues than those decided by the Supreme Court a day after this Federal Circuit decision was issued. (Please see this article for a discussion of Caraco.)

The Hatch-Waxman ANDA Framework

The Orange Book

When a brand manufacturer obtains FDA approval for a new drug product or method treatment, it submits to the FDA a list of relevant patents and their expiration dates. The FDA does not investigate or verify the identified patents, but publishes the information in its “Approved Drug Products With Therapeutic Equivalence Evaluations,” a/k/a, the Orange Book.

A generic drug manufacturer may seek FDA approval to market a generic version of an approved drug by filing an Abbreviated New Drug Application (ANDA). An ANDA must include a certification regarding each patent listed in the Orange Book for the product at issue. Relevant to this case is the “paragraph IV” certification, which is an assertion that the listed patent is invalid or will not be infringed by the generic product.

ANDA Litigation

According to the Hatch-Waxman Act, the filing of an ANDA with a paragraph IV certification constitutes an act of patent infringement. Thus, a patent owner can bring an infringement action against an ANDA applicant who has made a paragraph IV certification, permitting resolution of the patent issues before the generic product enters the market. Two additional principles of this “artificial” infringement are relevant to this case:

  • By its express terms, 35 USC § 271(e)(2) makes it an act of infringement to file an ANDA “for a drug claimed in a patent or the use of which is claimed in a patent”
  • In accordance with the 2003 Federal Circuit decision in Warner-Lambert Co. v. Apotex, Corp., the artificial infringement pertains only to “a patented use that has been approved by the FDA.”

The Product At Issue

The product at issue is Bayer’s Yasmin product, which is approved for oral contraception.

The patent at issue is U.S. Patent 5,569,652, which claims methods of “simultaneously achieving . . . a gestagenic effect, antiandrogenic effect, and an antialdosterone effect ….” (Two other patents listed in the Orange Book for Yasmin are not at issue in this case.)

The District Court Litigation

The defendants in this case—Lupin, Watson and Sandoz—each filed ANDAs with paragraph IV certifications regarding the Orange Book listed patents, including that ’652 patent. Bayer sued each defendant, alleging infringement under 35 USC § 271(e)(2) of the ’652 patent  (only).

Watson and Sandoz moved for judgment of noninfringement on the pleadings (under Federal Rule of Civil Procedure 12(c)), arguing that “their ANDAs related to the use of the generic form of Yasmin only for oral contraception and not for the combination of uses claimed in the ’652 patent.” The district court agreed, and granted their motions. In so doing, the court “noted that the FDA had approved the use of Yasmin only for oral contraception, and not for the simultaneous treatment of three conditions . . . [as] claimed in the ’652 patent.” Moreover, because “there was nothing in the record to indicate that the defendants sought to promote their generic versions of Yasmin based on the anti-androgenic or anti-aldosterone properties claimed in the ’652 patent, the court rejected Bayer’s claim that the defendants were liable for inducement of infringement.” Based on that ruling, Bayer and Lupin stipulated to, and the court entered, final judgment in that suit as well.

The Federal Circuit Decision

The court summarized the governing principles as follows:

Based on Warner-Lambert and Allergan, the defendants’ conduct would constitute infringement under section 271(e)(2)(A) (or inducement of infringement under section 271(b)) only if the defendants’ ANDAs sought approval for the use protected by the ’652 patent, i.e., for the combination of a gestagenic effect, an anti-androgenic effect, and an anti-aldosterone effect in patients needing that combination of effects.

Given the ANDA framework, “the use or uses for which the ANDAs seek FDA approval are necessarily the same as the uses for which the FDA has given its approval by granting Bayer’s NDA.” Thus, the “narrow” question before the court was:

whether the FDA has approved the use of Yasmin to achieve the combination of the three effects claimed in the ’652 patent.

In deciding this issue, the Federal Circuit noted that the “Indications and Usage” section of the approved Yasmin label states:

Yasmin is indicated for the prevention of pregnancy in women who elect to use an oral contraceptive.

The court noted that “that characterization tracks the FDA’s approval letter for Yasmin, which stated that the NDA ‘provides for the use of Yasmin . . . for oral contraception.’”

Bayer cited information set forth in the “Pharmacodynamics” subsection of the “Clinical Pharmacology” section of the label, which states that drospirenone (one of the two active ingredients in Yasmin):

is a spironolactone analogue with antimineralocorticoid activity. Preclinical studies in animals and in vitro have shown that drospirenone has no androgenic, estrogenic, glucocorticoid, and antiglucocorticoid activity. Preclinical studies in animals have also shown that drospirenone has antiandrogenic activity.

The Federal Circuit disagreed that the presence of this information indicated that the FDA had approved Yasmin for those uses. To the contrary, the court found no indication that the FDA had determined that Yasmin is “safe or effective in inducing those effects.”

The court concluded:

The defendants’ ANDAs seek approval to market the generic form of Yasmin solely for contraceptive use, and there is no valid patent on the use of the drug for that purpose alone. The FDA-approved label for Yasmin does not indicate to physicians that the specific use claimed in the ’652 patent, i.e., producing contraceptive, anti-mineralocorticoid, and anti-androgenic effects in premenopausal and menopausal women with a specific need of all three effects, is safe and effective. Therefore, we agree with the district court that the FDA has not approved such use and that the defendants cannot be held liable for infringement of the patent.

Judge Newman’s Dissent

Judge Newman wrote a dissenting opinion that disagreed with the majority decision on procedural, factual, and legal grounds.

  • Procedurally, Judge Newman disagrees that this case properly was decided at the pleadings stage, because infringement is a question of fact and the court did not accept all of Bayer’s factual assertions as true.
  • Factually, Judge Newman disagrees that the FDA did not approve the antiandrogenic and antialdosterone effects recited in the ’652 patent.
  • Legally, Judge Newman disagrees that the infringement inquiry should focus on the FDA-approved labeling instead of the actual (planned) marketing and use of the generic product.

(For a discussion of labeling that was found to support a claim of induced infringement, please see this article on Astra Zeneca LP v. Apotex, Inc.)

Now What?

It will be interesting to see what happens next. Once the FDA approves the ANDAs and the defendants prepare to market generic versions of Yasmin, Bayer may have several additional options to keep them off the market. As noted above, there are two other patents listed in the Orange Book for Yasmin. While Bayer chose not to litigate those patents in the ANDA framework, it still could assert them in an infringement action under 35 USC § 271(a) (direct infringement). Moreover, Bayer even may be able to assert the ’652 patent in infringement actions under 35 USC § 271(b) (induced infringement), because the infringement inquiry will not be restricted by the FDA-approved labeling, but could include broader consideration of, for example, the defendants’ marketing programs.