Apotex, Watson Lysteda Generics as Sold Held Not to Infringe Ferring's Patents

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By Tony Dutra

Aug. 22 — Ferring B.V. lost patent infringement challenges to generic versions of its Lysteda menstrual bleeding treatment in two Aug. 22 Federal Circuit rulings.

The court held that Watson Laboratories Inc.-Florida's version releases the active ingredient slower than the underlying patents cover (Ferring B.V. v. Watson Labs., Inc.,Fed. Cir., No. 2014-1416, 8/22/14).

Conversely, the court said, Apotex Inc.'s version releases the ingredient too quickly to be infringing (Ferring B.V. v. Watson Labs., Inc.,Fed. Cir., No. 2014-1377, 8/22/14).

In both cases, Ferring's arguments based on the initial abbreviated new drug application filed by each company fell flat, and the district court erred, the court said, to the extent it relied on those early ANDAs and not the products to be sold in the market.

First ANDAs Before Patents Issued

Ferring owns patents (U.S. Patents 7,947,739; 8,022,106; and 8,273,795) directed to modified release formulations of tranexamic acid, the active ingredient in the drug marketed as a treatment for heavy menstrual bleeding, or menorrhagia, under the brand name Lysteda.

In these cases, the key limitation related to the timing of dissolution of the active ingredient. The inventors defined specific percentages to be dissolved after specific numbers of minutes. Their goal was to reduce side effects by matching the rate of absorption in the gastrointestinal tract.

Apotex and Watson filed ANDAs before the first patent was granted. Once the '739 patent was granted, per Hatch-Waxman procedure, Ferring filed patent infringement lawsuits, both in the U.S. District Court for the District of Nevada.

Judge Robert Clive Jones found the patents not invalid for obviousness and the following as to infringement:

• The product identified in Apotex's original ANDA infringed, but the court dismissed the case when, after trial, Apotex agreed to amend its ANDA to a formulation that released 75 percent of the tranexamic acid within 45 minutes. The relevant asserted claim was limited by “less than about 70% by weight … at about 45 minutes,” the court emphasized.

• The product identified in Watson's original ANDA infringed, and Watson's post-trial amendment was not sufficient to avoid an infringement finding.

Ferring appealed the Apotex decision; Watson appealed the decision against it.

ANDA for Jurisdiction, All Evidence for Infringement

The same Federal Circuit panel heard the appeals and were unanimous in both. Judge Timothy B. Dyk wrote the Apotex decision and Judge Alan D. Lourie wrote the Watson decision, with Judge Jimmie V. Reyna joining.

The district court's first error, according to the court, was to treat the original ANDA as anything more than “a technical act of infringement for jurisdiction purposes” under Hatch-Waxman. The trial judge must consider “all of the relevant evidence”—including but not limited to the ANDA—to find infringement, the Watson opinion said.

ANDA Silence on Patent Limitation Golden

One problem for Ferring in both cases was that the original ANDAs were silent as to the dissolution rates.

The court said that the district court erred in relying on Sunovion Pharm. v. Teva Pharm. USA, Inc., 731 F.3d 1271, 2013 BL 260375, 108 U.S.P.Q.2d 1486 (Fed. Cir. 2013) (188 PTD, 9/27/13), where a product described in the ANDA “could” infringe the patents in suit, despite the generic drug company's certifying that it would not infringe.

Quoting from that case, the court here said, “Sunovion only applies when ‘an ANDA specification defines a compound such that it meets the limitations of an asserted claim.' 731 F.3d at 1280.” Instead the court said, the proper precedent when one cannot tell from the ANDA whether the product would infringe is Glaxo, Inc. v. Novopharm, Ltd., 110 F.3d 1562, 42 U.S.P.Q.2d 1257 (Fed. Cir. 1997), where there was still an open question despite the description in the ANDA.

The relevant inquiry in that case, the court here said, quoting Glaxo, is “whether the patentee has proven by a preponderance of the evidence that the alleged infringer will likely market an infringing product. What is likely to be sold, or, preferably, what will be sold, will ultimately determine whether infringement exists.” Id. at 1570.

Watson's Amended ANDA With Slower Release

The lower court's error was immediately relevant to Watson, whose amended ANDA described a commercial product with a coating and core hardness that released no more than 44 percent of the tranexamic acid in the first 90 minutes, while the patent claims required at least 50 percent in that time frame.

Watson did have one additional problem in that testing done on samples of its actual product sold showed four out of “hundreds” actually did infringe. But Watson's expert offered evidence that the four were not adequately coated. The court rejected Ferring's argument that “reliance on such anomalies proves infringement by a preponderance of the evidence in this case.”

Apotex Needs Claim Construction Affirmed

Apotex still had another problem, though. The “75 percent over 45 minute” profile of its amended ANDA was arguably close to the “about 70%” in the patent claim.

The district court construed “about” as equivalent to “approximately,” while Ferring argued that it should have been “plus or minus 10 percent” from the reference point.

Ferring was relying on a definition in the United States Pharmacopeia 27 Type II Paddle Method, but the court determined that the patent holder was misinterpreting the text. The USP did not allow for a “tolerance” around 70 percent, the court said, and it affirmed that “the term ‘about' should be given its ordinary and accepted meaning of ‘approximately' unless the patentee clearly redefines ‘about' in the specification.”

Again, Ferring's evidence that Apotex's 75 percent dissolution rate was “approximately” 70 percent was lacking.

The Apotex opinion made one additional point clear. Ferring argued that 35 U.S.C. §271(e)(4)(A) requires—given a finding of infringement—resetting the effective date of Food and Drug Administration approval of a generic until after the patents have expired. Therefore, it said, infringement by the original ANDA would be sufficient to reset the date, regardless of the amendment.

The court linked that Hatch-Waxman section to Section 271(e)(2) and concluded that “‘an application' means the ANDA as filed and all amendments to that application that have been allowed by the FDA.”

Nonobvious, No Worries About Future Infringement

Finally, it was Watson that contested the validity of the asserted claims for obviousness.

The court's analysis was straightforward. The court said, “[Watson's] cited prior art references neither set forth the limitations required by the asserted claims, nor provided any reason or motivation to combine those teachings to derive the claimed formulations with specific dissolution profiles.”

In both cases, Ferring argued that either generic firm could change its mind later and market a drug that would infringe.

However, Apotex agreed to notify Ferring and the district court if it later filed an amendment to the ANDA with the FDA. The court said, “any allegedly infringing conduct is unlikely to recur, given the restrictions that Apotex has placed on the amendment and the FDA's own governing statute.”

And, the court noted, Apotex would be subject to criminal charges if it marketed a product that had not been approved by the FDA.

James B. Monroe and Paul W. Browning of Finnegan, Henderson, Farabow, Garrett & Dunner LLP, Washington, represented Ferring.

Donald R. McPhail of Cozen O'Connor, Washington, represented Apotex. B. Jefferson Boggs Jr. of Merchant & Gould P.C., Alexandria, Va., represented Watson.

Watson decision is available at http://www.bloomberglaw.com/public/document/Ferring_BV_v_Watson_Laboratories_Inc_Docket_No_1401416_Fed_Cir_Ap.

Apotex decision is available at http://www.bloomberglaw.com/public/document/Ferring_BV_v_Watson_Laboratories_Inc_Docket_No_1401377_Fed_Cir_Ma/2.

To contact the reporter on this story: Tony Dutra in Washington at adutra@bna.com

To contact the editor responsible for this story: Naresh Sritharan at nsritharan@bna.com