The Federal Circuit upheld a judgment upholding the validity of U.S. Reissue Pat. No. 34,712 in favor of Forest Laboratories and H. Lundbeck A/S and enjoining Ivax Pharmaceuticals and Cipla Ltd. from infringing the ’712 patent — but only as it applies to escitalopram oxalate. See Forest Laboratories v. Ivax Pharmaceuticals and Cipla, Ltd. (07-1059).

Ivax filed an Abbreviated New Drug Application 76-765 (ANDA) for approval to market generic tablets containing 5, 10, or 20 milligrams of escitalopram oxalate (EO). The ANDA certified that the claims of the ’712 patent are invalid and/or not infringed by the products.

Forest filed suit that the ANDA infringed the ’712 patent, which relates to a substantially pure (+)-enantiomer of citalopram (escitalopram) and nontoxic acid additional salts thereof. Stereoisomers are compounds that contain the same constituent atoms and the same bonding between those atoms but have different spatial arrangements.

Enantiomers are stereoisomers that are nonsuperimposable mirror images of one another. Enantiomers exhibit different optical activity; the enantiomer that rotates a plane of polarized light in the clockwise direction is the (+)-enantiomer; the enantiomer that rotates a plane of polarized light in the counterclockwise direction is the (-)-enantiomer.

Enantiomers may also be designated as the S-enantiomer and the R-enantiomer according to a different criterion relating to the location of the chiral centers. In the case of citalopram, the (+)-enantiomer is also the S-enantiomer. A mixture of equal amounts of two enantiomers is called a racemic mixture or a racemate, and separating the two enantiomers from a racemate is referred to as resolving the compound.

Forest also owned the now expired U.S. Pat. No. 4,136,193 on the racemic form of citalopram and U.S. Patent 4,650,884 that claims a method for making racemic citalopram using an intermediate racemic 1,4-diol.

EO, which is the oxalate salt form of escitalopram, is one of the compounds encompassed by the claims of the ’712 patent. It is an antidepressant by virtue of being a selective serotonin reuptake inhibitor. Independent claim 1 of the ’712 patent reads as follows:

A compound selected from substantially pure (+)-1-(3-Dimethylaminopropyl)-1-(4’-fluorophenyl)-1,3-dihydroisobenzofuran-5-carbonitrile and non-toxic acid addition salts thereof.

The Federal Circuit agreed that Ivax and Cipla had failed to prove that the ’712 patent is anticipated because the prior art did not disclose substantially pure escitalopram as claimed in claim 1 and it did not enable a person having ordinary skill in the art to obtain that compound.

The Federal Circuit upheld the district court’s finding that chiral HPLC was a relatively new and unpredictable technique at the time of the invention and referenced unsuccessful attempts to resolve racemic citalopram, even hrough the method of diasteriomeric salt formation. Thus, the court found that attempting to separate the enantiomers of citalopram based on the knowledge of one of ordinary skill in the art would have required undue experimentation. The district court concluded that Ivax and Cipla had failed to prove by clear and convincing evidence that any of the asserted claims of the ’712 patent were obvious.

In looking at the scope of the injunction, the Fed Circuit held:

On Reducing the Scope of the Products:

We do not agree with the scope of the district court’s injunction that includes products other than escitalopram oxalate. “Although the standard of review for the issuance and scope of an injunction is abuse of discretion, whether the terms of the injunction fulfill the mandates of Federal Rule of Civil Procedure 65(d) is a question of law that this court reviews de novo.” Signtech USA, Ltd. v. Vutek, Inc., 174 F.3d 1352, 1356 (Fed. Cir. 1999). In International Rectifier, we held that “the only acts [an] injunction may prohibit are infringement of the patent by the adjudicated [products] and infringement by [products] not more than colorably different from the adjudicated [products]. 383 F.3d at 1316. In order to comply with Rule 65(d), the injunction should explicitly proscribe only those specific acts.”

Thus, while the injunction may properly extend to the “approved drug,” it should not extend to the remainder of the products covered by the patent. The injunction is therefore modified to delete the language “any products that infringe the ’712 patent, including.”

On Adding Cipla to the Injunction:

However, we find that it was not inappropriate for the district court to include Cipla within the scope of the injunction. Section 271(e)(2) may support an action for induced infringement. … Under the standards for inducement which we apply to 35 U.S.C. § 271(b), Cipla has therefore actively induced the acts of Ivax that will constitute direct infringement upon approval of the ANDA, and it was thus not inappropriate for the district court to include Cipla within the scope of the injunction.

[J]ust as Ivax will be liable for, and hence is being enjoined from, the commercial exploitation of escitalopram when it is approved by the FDA and during the life of the patent, so should Cipla be enjoined. They are partners. Cipla would be contributing to the infringement by Ivax, so the injunction should cover both partners. It is true that, as the dissent states, § 271(e)(2) defines Ivax’s filing of its ANDA as an infringement, and Cipla did not file the ANDA; however, when the question of an injunction against commercial activity arises, Cipla is as culpable, and hence entitled to be enjoined, as Ivax.

Is there an inconsistency here?

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One Comment

  1. Let me put the other side here.
    Suppose, Cipla was NOT enjoined, but the patent was held valid and so IVAX/ Teva were not gaining market entry.
    In this case too, CIPLA would be under indirect injunction since there would no [immediate] buyer for its active material – Carvedilol.

    So, even if CIpla would not have been enjoined, an injunction on the formulation company indricetly binds the business of the API company as well.